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Mantke R, Schneider C, von Ruesten A, Hauptmann M. Patients with stage IV colorectal carcinoma selected for palliative primary tumor resection and systemic therapy survive longer compared with systemic therapy alone: a retrospective comparative cohort study. Int J Surg 2024; 110:6493-6500. [PMID: 38935125 PMCID: PMC11487045 DOI: 10.1097/js9.0000000000001838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024]
Abstract
OBJECTIVE To compare the survival of palliative stage IV colorectal cancer patients selected for primary tumor resection and systemic treatment (PTR+SYST) to patients with systemic treatment only (SYST). BACKGROUND About 20-25% of all colorectal cancer patients are diagnosed with stage IV disease. The benefit of primary tumor resection in the palliative situation is therefore of high concern. However, empirical evidence from randomized and observational studies is inconsistent. METHODS Mortality after PTR+SYST was compared to systemic treatment alone in a retrospective observational cohort of patients diagnosed 2012-2020 from the cancer registry in the federal state of Brandenburg (Germany), excluding patients with rectal cancer of the lower two-thirds, emergency procedures, unknown ECOG status, ECOG greater than 2, unknown metastatic status or unclear grading. RESULTS Of 480 patients, 416 died during an average follow-up of 23 months in mean. Twelve-month survival was 75% after PTR+SYST compared with 49% after SYST [hazard ratio (HR)=0.39, 95% CI 0.29-0.53, P <0.001]. The difference persisted to 36 months (28% vs. 13%, HR=0.53, 95% CI 0.43-0.66, P <0.001). Results were similar after multivariate adjustment, propensity score matching and delayed entry. CONCLUSION AND RELEVANCE Patients with stage IV colorectal carcinoma who are selected for primary tumor resection in combination with systemic therapy and who receive such treatment survive longer compared with patients who receive only systemic treatment. Whether the difference is due to the selection of patients or PTR remains unclear. At present, the current practice of selecting patients for PTR appears to do no harm.
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Affiliation(s)
- Rene Mantke
- Clinic for General and Visceral Surgery, University Hospital Brandenburg an der Havel, Brandenburg Medical School
- Faculty of Health Sciences Brandenburg, Brandenburg Medical School, Brandenburg
| | | | - Anne von Ruesten
- Clinical-Epidemiological Cancer Registry Brandenburg Berlin, Cottbus
| | - Michael Hauptmann
- Faculty of Health Sciences Brandenburg, Brandenburg Medical School, Brandenburg
- Institute of Biostatistics and Registry Research, Brandenburg Medical School, Neuruppin, Germany
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Yokoyama S, Watanabe T, Matsumura S, Tamiya M, Nagano S, Hori Y. Cancer histology in metastatic lymph node predicts prognosis in patients with node-positive stage IV colorectal cancer. PeerJ 2024; 12:e17702. [PMID: 39006028 PMCID: PMC11243965 DOI: 10.7717/peerj.17702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 06/17/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Appropriate prognostic indicators are required for patients with stage IV colorectal cancer (CRC). Lymph node metastasis mainly involves four histological types of CRC. Some metastatic lymph nodes (mLNs) showing cribriform carcinoma are associated with distant metastasis in patients with node-positive CRC and are correlated with recurrence and survival in stage III disease. However, the significance of mLN histology in the prognosis of patients with node-positive stage IV disease remains unclear. METHODS We enrolled 449 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and November 2018. This study included 88 patients with node-positive stage IV CRC and synchronous or metachronous distant metastases. We retrospectively investigated the association between cancer histology in the mLNs based on our classification and cancer-specific survival (CSS) in patients with node-positive stage IV CRC. RESULTS Kaplan-Meier analysis showed that CSS was better in patients with CRC and all the mLNs showing tubular-type carcinoma. In contrast, patients with at least some mLNs showing poorly differentiated-type carcinoma had poor prognosis. Multivariate analysis showed that "all mLNs showing tubular-type carcinoma" was an independent good prognostic factor for CSS in patients with node-positive stage IV CRC. In addition, "at least some mLNs showing poorly differentiated-type carcinoma" was an independent poor prognostic factor for CSS in patients with node-positive stage IV disease. CONCLUSIONS The histological type of the mLN may indicate a better or poor prognosis for patients with stage IV CRC.
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Affiliation(s)
- Shozo Yokoyama
- Department of Surgery, National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
| | - Takashi Watanabe
- Department of Surgery, National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
| | - Shuichi Matsumura
- Department of Surgery, National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
| | - Masato Tamiya
- Department of Surgery, National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
| | - Shotaro Nagano
- Department of Surgery, National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
| | - Yuya Hori
- Department of Surgery, National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
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Shin JE, An HJ, Shim BY, Kim H, Park HS, Cho HM, Kye BH, Yoo RN, Moon JY, Kim SH, Lee J, Lee HC, Jung JH, Lee KM, Lee JM. Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:5057. [PMID: 37894424 PMCID: PMC10605032 DOI: 10.3390/cancers15205057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 10/01/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023] Open
Abstract
The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.
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Affiliation(s)
- Ji Eun Shin
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Ho Jung An
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Byoung Yong Shim
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Hyunho Kim
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Hyung Soon Park
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Hyeon-Min Cho
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Bong-Hyeon Kye
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Ri Na Yoo
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Ji-Yeon Moon
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Sung Hwan Kim
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (S.H.K.); (J.L.); (H.C.L.)
| | - Jonghoon Lee
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (S.H.K.); (J.L.); (H.C.L.)
| | - Hyo Chun Lee
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (S.H.K.); (J.L.); (H.C.L.)
| | - Ji-Han Jung
- Department of Hospital Pathology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea;
| | - Kang-Moon Lee
- Division of Gastroenterology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (K.-M.L.); (J.M.L.)
| | - Ji Min Lee
- Division of Gastroenterology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (K.-M.L.); (J.M.L.)
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Wang X, Qi R, Xu Y, Lu X, Shi Q, Wang Y, Wang D, Wang C. Clinicopathological characteristics and prognosis of colon cancer with lung metastasis without liver metastasis: A large population-based analysis. Medicine (Baltimore) 2022; 101:e31333. [PMID: 36281166 PMCID: PMC9592286 DOI: 10.1097/md.0000000000031333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Distant metastasis explains the high mortality rate of colon cancer, in which lung metastasis without liver metastasis (LuM) is a rare subtype. This study is aimed to identify risk factors of LuM and LLM (lung metastasis with liver metastasis) from colon cancer, and to analyze the prognosis of patients with LuM by creating a nomogram. Patients' information were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic regression analysis was used to determine the risk factors for LuM and LLM. Prognostic factors for cancer-specific survival (CSS) and overall survival (OS) were identified by multivariate Cox proportional hazards regression and nomogram models were established to predict CSS and OS. Multivariate logistic regression analysis showed that blacks, splenic flexure of colon tumor, tumor size >5 cm, T4, N3, and higher lymph node positive rate were associated with the occurrence of LuM. Meanwhile, age >65 years old, female, splenic flexure of colon, higher lymph node positive rate, and brain metastasis were independent risk factors for CSS. The C-index of the prediction model for CSS was 0.719 (95% CI: 0.691-0.747). In addition, age, primary site, tumor size, differentiation grade, N stage, and bone metastasis were significantly different between LuM and LLM. The nomograms we created were effective in predicting the survival of individuals. Furthermore, patients with LuM and LLM from colon cancer might require different follow-up intervals and examinations.
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Affiliation(s)
- Xiao Wang
- Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province, P. R. China
| | - Ruihua Qi
- Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province, P. R. China
| | - Ying Xu
- Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province, P. R. China
| | - Xingang Lu
- Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province, P. R. China
| | - Qing Shi
- Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province, P. R. China
| | - Ya Wang
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Department of Hospital Infection-Control, Cancer Hospital of the University of Chinese Academy of Sciences, Department of Hospital Infection-Control, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, P. R. China
| | - Da Wang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
- *Correspondence: Chunliang Wang, Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province 311499, P. R. China (e-mail: )
| | - Chunliang Wang
- Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province, P. R. China
- *Correspondence: Chunliang Wang, Department of Colorectal Surgery, The First People’s Hospital of Fuyang, Hangzhou, Zhejiang Province 311499, P. R. China (e-mail: )
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Huang X, Hu P, Yan F, Zhang J. Establishment and Validation of a Nomogram Based on Negative Lymph Nodes to Predict Survival in Postoperative Patients with non-Small Cell Lung Cancer. Technol Cancer Res Treat 2022; 21:15330338221074506. [PMID: 35060800 PMCID: PMC8796078 DOI: 10.1177/15330338221074506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Background: The importance of the negative lymph node (NLN) count has recently attracted attention. This study aimed to determine the prognostic value of NLN count in patients with non-small cell lung cancer (NSCLC) after radical surgery by constructing NLN-based prognostic models. Methods: This study included 33 756 patients pooled from the case listing session of the US Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and 545 patients collected from The First Affiliated Hospital of Shandong First Medical University between 2012 and 2016. X-tile software was used to calculate the optimal cutoff value for the NLN count. The associated clinical factors were determined using univariate and multivariate Cox analyses. Nomograms were developed using the SEER database and validated using hospital data. Results: The training cohort was divided into high and low NLN count subgroups based on the cancer-specific survival (CSS) and overall survival (OS), respectively. Multivariate analysis showed that NLN count was an independent prognostic factor, and the high NLN count subgroup had better CSS and OS than those of the low NLN count subgroup (HR = 0.632, 95% CI 0.551-0.724, P < .001 for CSS and HR = 0.641, 95% CI 0.571-0.720, P < .001 for OS). Nomograms were established, exhibiting good discrimination ability with a C-index of 0.789 (95% CI 0.778 −0.798) for CSS and 0.704 (95% CI, 0.694 −0.714) for OS. The calibration plots of the validation cohorts showed optimal agreement with the training cohort, with a C-index of 0.681 (95% CI 0.646 −0.716) for CSS and 0.645 (95% CI 0.614 −0.676) for OS. Conclusions: NLN count is a strong prognostic factor for OS and CSS in NSCLC patients and the prognostic model provides a useful risk stratification for NSCLC patients when applied to clinical practice.
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Affiliation(s)
- Xinyi Huang
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China
| | - Pingping Hu
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China
| | - Fei Yan
- Dezhou Seventh People’s Hospital, Dezhou, China
| | - Jiandong Zhang
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China
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Konishi T, Rodriguez-Bigas MA. Primary Tumor Resection in Colorectal Cancer with Unresectable Synchronous Metastasis: Time to Reconsider the Role of the Surgeon. Ann Surg Oncol 2021; 29:1-3. [PMID: 34671880 DOI: 10.1245/s10434-021-10949-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 10/05/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Tsuyoshi Konishi
- Department of Colon and Rectal Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Miguel A Rodriguez-Bigas
- Department of Colon and Rectal Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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To resect or not to resect? Insight on managing the asymptomatic primary tumor in colorectal cancer patients with synchronous unresectable metastases from the prospective Japan Clinical Oncology Group Trial. Surgery 2021; 170:1856-1857. [PMID: 34275616 DOI: 10.1016/j.surg.2021.06.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 06/15/2021] [Indexed: 11/23/2022]
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Klose J, Rieder S, Ronellenfitsch U. Surgical and interventional treatment options in unresectable gastrointestinal cancer. SURGERY IN PRACTICE AND SCIENCE 2021. [DOI: 10.1016/j.sipas.2021.100037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Prognostic value of regional lymph node involvement in patients with metastatic colorectal cancer: palliative versus curative resection. World J Surg Oncol 2021; 19:150. [PMID: 33985521 PMCID: PMC8120831 DOI: 10.1186/s12957-021-02260-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/05/2021] [Indexed: 12/11/2022] Open
Abstract
Background Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes. Methods We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN−) group and another 980 in the LN-positive (LN+) group. Results LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN− group. LN− patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN− group (LN− vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN− vs. LN+ 19.5% vs. 24.3%; p = 0.890). Conclusions Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN− patients. LN+ patients had poorer long-term outcomes compared with that in LN− patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN− patients.
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Kanemitsu Y, Shitara K, Mizusawa J, Hamaguchi T, Shida D, Komori K, Ikeda S, Ojima H, Ike H, Shiomi A, Watanabe J, Takii Y, Yamaguchi T, Katsumata K, Ito M, Okuda J, Hyakudomi R, Shimada Y, Katayama H, Fukuda H. Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial. J Clin Oncol 2021; 39:1098-1107. [PMID: 33560877 PMCID: PMC8078424 DOI: 10.1200/jco.20.02447] [Citation(s) in RCA: 129] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
It remains controversial whether primary tumor resection (PTR) before chemotherapy improves survival in patients with colorectal cancer (CRC) with asymptomatic primary tumor and synchronous unresectable metastases.
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Affiliation(s)
| | - Kohei Shitara
- National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Tetsuya Hamaguchi
- Saitama Medical University International Medical Center, Hidaka, Japan
| | - Dai Shida
- National Cancer Center Hospital, Tokyo, Japan
| | | | | | | | - Hideyuki Ike
- Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan
| | - Akio Shiomi
- Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Jun Watanabe
- Yokohama City University Medical Center, Yokohama, Japan
| | | | | | | | - Masaaki Ito
- National Cancer Center Hospital East, Kashiwa, Japan
| | - Junji Okuda
- Osaka Medical College Hospital, Osaka, Japan
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Matsuda A, Yamada T, Matsumoto S, Shinji S, Ohta R, Sonoda H, Takahashi G, Iwai T, Takeda K, Sekiguchi K, Yoshida H. Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review. J Anus Rectum Colon 2021; 5:1-10. [PMID: 33537495 PMCID: PMC7843144 DOI: 10.23922/jarc.2020-061] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/15/2020] [Indexed: 02/08/2023] Open
Abstract
Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.
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Affiliation(s)
- Akihisa Matsuda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Takeshi Yamada
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Satoshi Matsumoto
- Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Kamagari, Inzai, Japan
| | - Seiichi Shinji
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Ryo Ohta
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Hiromichi Sonoda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Goro Takahashi
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Takuma Iwai
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Kohki Takeda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Kumiko Sekiguchi
- Department of Surgery, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan
| | - Hiroshi Yoshida
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
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Mukkamalla SKR, Somasundar P, Rathore B. Prognostic Impact of Tumor Status, Nodal Status and Tumor Sidedness in Metastatic Colon Cancer. Cureus 2020; 12:e11444. [PMID: 33329946 PMCID: PMC7734889 DOI: 10.7759/cureus.11444] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Locally advanced primary tumors have been associated with poor overall survival (OS) in non-metastatic colon cancer. However, their impact on metastatic colon cancer (mCC) is not fully defined. The association between primary tumor location and prognosis in mCC is also evolving. Methods Using National Cancer Data Base, we identified a cohort of 25,377 patients diagnosed with mCC from 2004-2009. Chi-square test was used for descriptive analyses, while all potential prognostic factors were evaluated using Kaplan-Meier survival estimates and Cox proportional hazards regression modeling. Results The five-year OS for the entire study cohort was 12.3%. Factors associated with significant survival impact in multivariate analysis included age, gender, race, comorbidity index, academic level of treating institution, insurance status, income, year of diagnosis, primary tumor site, histologic differentiation, pathologic tumor stage (pT), pathologic nodal stage (pN), and modality of chemotherapy. pT1 lesions demonstrated poor prognosis in stage IV colon cancers, not statistically different when compared to survival outcomes observed in cases with pT4 lesions. Regional nodal involvement demonstrated poor OS in full cohort analysis and subgroup analysis independent of primary tumor location. Both right-sided and transverse colon tumors had similarly worse OS compared to left-sided tumors (right-sided: HR: 1.21, 95% CI: 1.17-1.25; transverse: HR: 1.21, 95% CI: 1.15-1.27). Conclusions T1 lesions arising from right-side or transverse colon portend a poor prognosis in mCC, while regional lymph node involvement by itself is an independent poor prognostic factor. Right-sided tumors are associated with poor outcomes than left-sided tumors, suggesting the role of underlying molecular or biologic variants.
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Affiliation(s)
- Shiva Kumar R Mukkamalla
- Hematology and Oncology, Ted and Margaret Jorgensen Cancer Center/Presbyterian Healthcare Services, Rio Rancho, USA
| | | | - Bharti Rathore
- Hematology and Medical Oncology, Roger Williams Medical Center, Providence, USA
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Yang Y, Lu Y, Jiang W, Zhu J, Yan S. Individualized prediction of survival benefit from primary tumor resection for patients with unresectable metastatic colorectal cancer. World J Surg Oncol 2020; 18:193. [PMID: 32746835 PMCID: PMC7401291 DOI: 10.1186/s12957-020-01972-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022] Open
Abstract
Background The impact of primary tumor resection (PTR) on the prognosis of unresectable metastatic colorectal cancer (mCRC) patients remains debatable. We aimed to develop several prognostic nomograms which could be useful in predicting whether patients might benefit from PTR or not. Methods Patients diagnosed as mCRC without resected metastasis were identified from the Surveillance Epidemiology and End Results database and randomly assigned into two groups: a training cohort (6369 patients) and a validation cohort (2774 patients). Univariate and multivariable Cox analyses were performed to identify the independent predictors and construct nomograms that could independently predict the overall survival (OS) of unresectable mCRC patients in PTR and non-PTR groups, respectively. The performance of these nomograms was assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results Based on the result of univariate and multivariable Cox analyses, two nomograms were respectively constructed to predict the 1-year OS rates of unresectable mCRC patients when receiving PTR and not. The first one included age, gender, tumor grade, proximal colon, N stage, CEA, chemotherapy, radiotherapy, histology type, brain metastasis, liver metastasis, lung metastasis, and bone metastasis. The second nomogram included age, race, tumor grade, primary site, CEA, chemotherapy, brain metastasis, and bone metastasis. These nomograms showed favorable sensitivity with the C-index range of 0.700–0.725. The calibration curves and DCAs also exhibited adequate fit and ideal net benefits in prognosis prediction and clinical application. Conclusions These practical prognosis nomograms could assist clinicians in making appropriate treatment decisions to effectively manage the disease.
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Affiliation(s)
- Yi Yang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Yujie Lu
- Department of Oncology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Wen Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Su Yan
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China.
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Indocyanine Green Fluorescence Imaging-Guided Laparoscopic Surgery Could Achieve Radical D3 Dissection in Patients With Advanced Right-Sided Colon Cancer. Dis Colon Rectum 2020; 63:441-449. [PMID: 31996582 DOI: 10.1097/dcr.0000000000001597] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND The optimal lymph node dissection with central vascular ligation is an important part for oncological outcomes after laparoscopic right-sided colon cancer surgery. Few studies have examined the clinical value of indocyanine green fluorescence imaging-guided D3 dissection for right-sided colon cancer. OBJECTIVES We assessed the clinical value of indocyanine green fluorescence imaging-guided laparoscopic surgery in improving the radicality of lymph node dissection for right-sided colon cancer by comparing the outcomes of conventional laparoscopic surgery. DESIGN The data were retrospectively reviewed and analyzed. SETTING This study was conducted at a single university hospital. PATIENTS A 1:2 matched case-control study included 25 patients undergoing fluorescence imaging-guided laparoscopic surgery and 50 patients undergoing conventional laparoscopic surgery for clinical T3 or T4 right-sided colon cancer between June 2016 and December 2017. MAIN OUTCOME MEASURES The extent of D3 dissection and pathological results (tumor stage, lymph node yield, and number of metastatic lymph nodes) were analyzed. RESULTS The 2 groups were similar in baseline characteristics. The numbers of harvested pericolic and intermediate lymph nodes were not different between the 2 groups. The numbers of central lymph nodes (14 vs 7, p < 0.001) and total harvested lymph nodes (39 vs 30, p = 0.003) were significantly higher in the fluorescence group than in the conventional group. In the multivariate analysis, the use of indocyanine green fluorescence imaging was an independently related factor for the retrieval of higher numbers of overall and central lymph nodes. The number of metastatic lymph nodes was not significantly different between the 2 groups. LIMITATIONS The results of this study were limited by its small patient numbers and retrospective nature. CONCLUSIONS Real-time indocyanine green fluorescence imaging of lymph nodes may improve the performance of more radical D3 lymph node dissection during laparoscopic right hemicolectomy for advanced right-sided colon cancer. See Video Abstract at http://links.lww.com/DCR/B150. LA CIRUGÍA LAPAROSCÓPICA GUIADA POR IMÁGENES DE FLUORESCENCIA VERDE INDOCIANINA PODRÍA LOGRAR UNA DISECCIÓN RADICAL D3 EN PACIENTES CON CÁNCER DE COLON AVANZADO DEL LADO DERECHO: La disección óptima de los ganglios linfáticos con ligadura vascular central es una parte importante para los resultados oncológicos después de la cirugía laparoscópica de cáncer de colon del lado derecho. Pocos estudios han examinado el valor clínico de la disección D3 guiada por imágenes de fluorescencia verde indocianina para el cáncer de colon del lado derecho.Evaluamos el valor clínico de la cirugía laparoscópica guiada por imagen de fluorescencia verde indocianina para mejorar la radicalidad de la disección de ganglios linfáticos para el cáncer de colon del lado derecho mediante la comparación de los resultados de la cirugía laparoscópica convencional.Los datos se revisaron y analizaron retrospectivamente.Este estudio se realizó en un solo hospital universitario.Un estudio de casos y controles emparejado 1:2 incluyó a 25 pacientes sometidos a cirugía laparoscópica guiada por imágenes de fluorescencia y 50 pacientes sometidos a cirugía laparoscópica convencional para cáncer de colon derecho clínico T3 o T4 entre Junio de 2016 y Diciembre de 2017.Se analizó el alcance de la disección D3 y los resultados patológicos (estadio tumoral, rendimiento de los ganglios linfáticos y número de ganglios linfáticos metastásicos).Los dos grupos fueron similares en las características basicas. El número de ganglios linfáticos pericólicos e intermedios recolectados no fue diferente entre los dos grupos. El número de ganglios linfáticos centrales (14 vs 7, p < 0.001) y el total de ganglios linfáticos recolectados (39 vs 30, p = 0.003) fueron significativamente mayores en el grupo de fluorescencia que en el grupo convencional. En el análisis multivariante, el uso de imágenes de fluorescencia verde indocianina fue un factor independiente relacionado para la recuperación de un mayor número de ganglios linfáticos centrales y globales. El número de ganglios linfáticos metastásicos no fue significativamente diferente entre los dos grupos.Los resultados de este estudio fueron limitados por su pequeño número de pacientes y su naturaleza retrospectiva.Las imágenes de fluorescencia verde indocianina en tiempo real de los ganglios linfáticos pueden mejorar el rendimiento de la disección más radical de los ganglios linfáticos D3 durante la hemicolectomía derecha laparoscópica para el cáncer de colon avanzado del lado derecho. Consulte Video Resumen en http://links.lww.com/DCR/B150.
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Hao Y, Zhang J, Du R, Huang X, Li H, Hu P. Impact of negative lymph nodes on colon cancer survival and exploring relevant transcriptomics differences through real-world data analyses. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:525. [PMID: 31807507 DOI: 10.21037/atm.2019.09.138] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background The prognostic role and underlying heterogeneity of negative lymph nodes (NLNs) on colon cancer is not well understood. The purpose of this study was to construct NLN-based prognostic models and reveal relevant mechanisms affecting NLNs by analyzing omic data. Methods This inception cohort study included 314,398 colon cancer patients from the US Surveillance, Epidemiology, and End Results (SEER) database. Receiver operating characteristic (ROC) curve was used to determine the cut-off of NLNs. Nomograms were constructed and validated using SEER data and the Cancer Genome Atlas (TCGA) data, respectively. The differentially expressed genes (DEGs) were analyzed using edgeR. Enrichment analyses were performed by Metascape. Results Multivariate analysis confirmed the high NLN had improved cancer-specific survival (CSS) and overall survival (OS) compared to low NLN [hazard ratio (HR) =0.610, 95% confidence interval (CI), 0.601-0.620] for CSS and (HR =0. 682, 95% CI, 0.674-0.690) for OS. Nomograms were established for CSS and OS with the c-statistic 0.790 (95% CI, 0.788-0.792) for CSS and 0.734 (95% CI, 0.732-0.736) for OS. High NLN was associated with less B cell (P=0.002) and macrophage infiltration (P<0.0001), high microsatellite instability (MSI) (OR =4.325, P=0.001), and hypermutation (OR =4.285, P=0.001; high vs. low). Transcriptomics analysis demonstrated histone modifiers were the most significant different biological processes between the high and low NLN group. Conclusions The NLN-based models can aid in personalized risk stratification for colon cancer. This study postulates that high NLN may represent a biological subtype with less macrophage infiltration, high MSI status, hypermutation, and histone modifier gene enriched expression, and thus warrants further investigation.
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Affiliation(s)
- Yuying Hao
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China
| | - Jiandong Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China
| | - Rui Du
- Division of Oncology, Department of Graduate, Weifang Medical College, Weifang 261053, China
| | - Xinyi Huang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China
| | - Hui Li
- Department of Radiation Oncology, Taishan Medical University, Tai'an 271016, China
| | - Pingping Hu
- Department of Radiation Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China
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Shida D, Boku N, Tanabe T, Yoshida T, Tsukamoto S, Takashima A, Kanemitsu Y. Primary Tumor Resection for Stage IV Colorectal Cancer in the Era of Targeted Chemotherapy. J Gastrointest Surg 2019; 23:2144-2150. [PMID: 30484063 DOI: 10.1007/s11605-018-4044-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 11/02/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND In the current era of targeted therapies, the benefits of resection of primary tumors in patients with unresectable stage IV colorectal cancer, specifically with regard to overall survival, are unknown. METHODS Our study population comprised 208 consecutive patients with unresectable stage IV colorectal cancer who received chemotherapy containing at least one molecular target agent, bevacizumab, cetuximab, and panitumumab, at the National Cancer Center Hospital from 2006 to 2013. To lessen the effects of confounding factors between two treatment groups (resection versus non-resection) such as performance status, presence of severe symptoms, M subcategories (M1a versus M1b, M1c) according to the TNM classification, primary tumor site, and CEA value, we conducted three different propensity score analyses (regression adjustment, stratification, and matching). RESULTS Of the 208 patients, 108 (52%) underwent resection of the primary tumor, while 100 (48%) did not. Regression adjustment revealed that resection was not associated with longer overall survival (hazard ratio of 0.70 (95% CI [0.49-1.00]; p = 0.051)). Stratification analysis of five strata revealed inconsistent results (hazard ratios ranged from 0.50 to 1.58); specifically, resection was associated with longer overall survival in four strata, but with shorter survival in one stratum. The propensity score-matched cohort (64 matched pairs) yielded a hazard ratio of 0.76 (95% CI [0.51-1.15]; p = 0.197). CONCLUSIONS All three analyses revealed that, in the current era of chemotherapy with target agents, primary tumor resection was only marginally influential and did not significantly improve overall survival over chemotherapy alone.
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Affiliation(s)
- Dai Shida
- Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan.
| | - Narikazu Boku
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Taro Tanabe
- Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Takefumi Yoshida
- Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Shunsuke Tsukamoto
- Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Atsuo Takashima
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
| | - Yukihide Kanemitsu
- Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan
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Ge H, Yan Y, Xie M, Guo L, Tang D. Construction of a nomogram to predict overall survival for patients with M1 stage of colorectal cancer: A retrospective cohort study. Int J Surg 2019; 72:96-101. [PMID: 31678689 DOI: 10.1016/j.ijsu.2019.10.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 10/17/2019] [Accepted: 10/22/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The M1 stage of colorectal cancer (CRC) has a poor prognosis. The aim of this study is to develop a reliable tool for the prediction for CRC patients with M1 stage, thus assisting the strategy of clinical diagnosis and treatment. METHODS CRC patient information collected in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 was extracted and evaluated. Multivariate analysis with Cox proportional hazards regression identified risk factors that predicted overall survival (OS) and the results were used to construct a nomogram to predict 3-, and 5-year OS in CRC patients with M1 stage. The Kaplan-Meier curve was plotted to evaluate OS differences. RESULTS A total of 19,796 patients from the SEER database were included for analysis. All patients were randomly allocated to 2 cohorts, the training cohort (n = 13,860) and the validation cohort (n = 5936). Patients' age at diagnosis; gender; race; tumor site; tumor grade; T and N stage; brain, lung, bone, and liver metastasis status; marital status; and therapy were associated with survival in the multivariate models. All these factors were incorporated to construct a nomogram. Additionally, we divide all 19,796 patients into high-risk group and low-risk group according to our nomogram, and plotted Kaplan-Meier curve. The result indicated that patients with higher risk had worse survival outcomes. CONCLUSIONS Our predictive model has the potential to provide an individualized risk estimate of survival in CRC patients with M1 stage.
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Affiliation(s)
- Hua Ge
- Department of Gastrointestinal Surgery, The First People's Hospital of Zunyi, Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
| | - Yan Yan
- Quality Control Department, The First People's Hospital of Zunyi, Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China
| | - Ming Xie
- Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China
| | - Lingfei Guo
- Department of Gastrointestinal Surgery, The First People's Hospital of Zunyi, Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China
| | - Dai Tang
- Department of Gastrointestinal Surgery, The First People's Hospital of Zunyi, Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China
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Simillis C, Kalakouti E, Afxentiou T, Kontovounisios C, Smith JJ, Cunningham D, Adamina M, Tekkis PP. Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis. World J Surg 2019; 43:1829-1840. [DOI: 10.1007/s00268-019-04984-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Maroney S, de Paz CC, Reeves ME, Garberoglio C, Raskin E, Senthil M, Namm JP, Solomon N. Benefit of Surgical Resection of the Primary Tumor in Patients Undergoing Chemotherapy for Stage IV Colorectal Cancer with Unresected Metastasis. J Gastrointest Surg 2018; 22:460-466. [PMID: 29124549 DOI: 10.1007/s11605-017-3617-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Accepted: 10/24/2017] [Indexed: 01/31/2023]
Abstract
PURPOSE Resection of the primary tumor in patients with unresected metastatic colorectal cancer is controversial, and often performed only for palliation of symptoms. Our goal was to determine if resection of the primary tumor in this patient population is associated with improved survival. METHODS This is a retrospective cohort study of the National Cancer Data Base from 2004 to 2012. The study population included all patients with synchronous metastatic colorectal adenocarcinoma who were treated with systemic chemotherapy. The study groups were patients who underwent definitive surgery for the primary tumor and those who did not. Patients were excluded if they had surgical intervention on the sites of metastasis or pathology other than adenocarcinoma. Primary outcome was overall survival. RESULTS Of the 65,543 patients with unresected stage IV colorectal adenocarcinoma undergoing chemotherapy, 55% underwent surgical resection of the primary site. Patients who underwent surgical resection of the primary tumor had improved median survival compared to patients treated with chemotherapy alone (22 vs 13 months, p < .0001). The surgical survival benefit was present for patients who were treated with either multi-agent or single-agent chemotherapy (23 vs 14 months, p < 0.001; 19 vs 9 months, p < 0.001). Surgical resection of the primary tumor was also associated with improved survival when using multivariate analysis with propensity score matching (OR = 0.863; 95% CI [0.805-.924]; HR = 0.914; 95% CI [0.888-0.942]). CONCLUSIONS Our results show that in patients with synchronous unresected stage IV colorectal adenocarcinoma undergoing single- or multi-agent chemotherapy, after adjusting for confounding variables, definitive resection of the primary site was associated with improved overall survival. Large randomized controlled trials are needed to determine if there is a causal relationship between surgery and increased overall survival in this patient population.
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Affiliation(s)
- Sean Maroney
- Department of Surgery, Loma Linda University Health, 11175 Campus Street, Suite 21108, Loma Linda, CA, 92350, USA.
| | | | - Mark E Reeves
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Carlos Garberoglio
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Elizabeth Raskin
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Maheswari Senthil
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Jukes P Namm
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Naveenraj Solomon
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
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Dev K, Veerenderkumar KV, Krishnamurthy S. Incidence and Predictive Model for Lateral Pelvic Lymph Node Metastasis in Lower Rectal Cancer. Indian J Surg Oncol 2018; 9:150-156. [PMID: 29887692 DOI: 10.1007/s13193-017-0719-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 12/12/2017] [Indexed: 01/22/2023] Open
Abstract
The lateral pelvic lymph node recurrence after curative resection in rectal cancer has been reported in more than 20% of cases and the lateral pelvic lymph node (LPLN) metastasis is an independent risk factor for local recurrence. A prospective cohort study with diagnosis of lower rectal cancer stages II and III performed to identify the factors with significant correlation with LPLN metastasis was categorised based on the number of positive factors and proposed a risk stratification model to uncover a possible benefit of LPLD in specific patient subgroups. Forty-three patients with lower rectal cancer underwent curative surgery, total mesorectal excision with bilateral lateral pelvic lymph node dissection. Pre-operative, female gender, raised serum CEA (> 5 ng/mL), cT4, enlarged mesorectal lymph nodes, borderline enlarged LPLN on MRI, lower location (< 5 cm from anal verge), large size (> 5 cm) and non-circumferential lesion were significant predictors for LPLN metastasis. Histopathological, higher tumour grade, higher pT and pN stage, and the presence of LVI were significant factors. On cox-proportional hazard model analysis, female gender, large tumour, cT4, enlarged mesorectal lymph nodes, borderline enlarged LPLN, pN1 and positive LVI were associated with significant hazard. In conclusion, a specific group of patients with lower rectal cancer of stages II and III might be have treated with LPND in spite of concurrent chemo-radiation to achieve satisfactory oncological outcome. The proposed stratification grouping is strongly guiding the patient for lateral pelvic lymph node dissection. Further study to prove the oncological advantage of LPND is warranted at large scale.
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Affiliation(s)
- Kapil Dev
- Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
| | - K V Veerenderkumar
- Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
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Kim MS, Park EJ, Kang J, Min BS, Lee KY, Kim NK, Baik SH. Prognostic factors predicting survival in incurable stage IV colorectal cancer patients who underwent palliative primary tumor resection. Retrospective cohort study. Int J Surg 2018; 49:10-15. [DOI: 10.1016/j.ijsu.2017.11.038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 11/14/2017] [Accepted: 11/27/2017] [Indexed: 02/02/2023]
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Nitsche U, Stöß C, Stecher L, Wilhelm D, Friess H, Ceyhan GO. Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer. Br J Surg 2017; 105:784-796. [PMID: 29088493 DOI: 10.1002/bjs.10682] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 06/01/2017] [Accepted: 07/07/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND It is not clear whether resection of the primary tumour (when there are metastases) alters survival and/or whether resection is associated with increased morbidity. This systematic review and meta-analysis assessed the prognostic value of primary tumour resection in patients presenting with metastatic colorectal cancer. METHODS A systematic review of MEDLINE/PubMed was performed on 12 March 2016, with no language or date restrictions, for studies comparing primary tumour resection versus conservative treatment without primary tumour resection for metastatic colorectal cancer. The quality of the studies was assessed using the MINORS and STROBE criteria. Differences in survival, morbidity and mortality between groups were estimated using random-effects meta-analysis. RESULTS Of 37 412 initially screened articles, 56 retrospective studies with 148 151 patients met the inclusion criteria. Primary tumour resection led to an improvement in overall survival of 7·76 (95 per cent c.i. 5·96 to 9·56) months (risk ratio (RR) for overall survival 0·50, 95 per cent c.i. 0·47 to 0·53), but did not significantly reduce the risk of obstruction (RR 0·50, 95 per cent c.i. 0·16 to 1·53) or bleeding (RR 1·19, 0·48 to 2·97). Neither was the morbidity risk altered (RR 1·14, 0·77 to 1·68). Heterogeneity between the studies was high, with a calculated I2 of more than 50 per cent for most outcomes. CONCLUSION Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.
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Affiliation(s)
- U Nitsche
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - C Stöß
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - L Stecher
- Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - D Wilhelm
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - H Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - G O Ceyhan
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
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Prognostic Significance of Peritoneal Metastasis in Stage IV Colorectal Cancer Patients With R0 Resection: A Multicenter, Retrospective Study. Dis Colon Rectum 2017; 60:1041-1049. [PMID: 28891847 DOI: 10.1097/dcr.0000000000000858] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Stage IV colorectal cancer encompasses various clinical conditions. The differences in prognosis after surgery between different metastatic organs have not been fully investigated. OBJECTIVE This study aimed to assess prognostic significance in peritoneal metastasis in R0 resected stage IV colorectal cancer. DESIGN We conducted a multicenter retrospective study of patients with R0 resected stage IV colorectal cancer; they were categorized into 3 groups according to the number and location of metastatic organs, including single-organ metastasis in the peritoneum, single-organ metastasis at sites except the peritoneum, and multiple-organ metastases. SETTINGS This study used data accumulated by the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer. PATIENTS A total of 1133 patients with R0 resected stage IV colorectal cancer were registered retrospectively between 1997 and 2007 in 20 referral hospitals. MAIN OUTCOME MEASURES Cancer-specific survival rates between the groups were measured. RESULTS The median cancer-specific survival of the single-organ metastasis in the peritoneum group was considerably shorter than that of the single-organ metastasis at a site other than the peritoneum group and was almost comparable to that of the multiple-organ metastases group (3.41 years, 6.20 years, and 2.99 years). In a multivariate analysis of cancer-specific survival, peritoneal dissemination was confirmed as an independent prognostic factor of survival. The median postrecurrence survival of single-organ metastasis in the peritoneum group was considerably shorter than that of the single-organ metastasis at a site other than the peritoneum group. Approximately half of the patients who experienced recurrence of single-organ metastasis in the peritoneum experienced peritoneal recurrence. LIMITATIONS This was a retrospective, population-based study that requires a prospective design to validate its conclusions. CONCLUSIONS Peritoneal metastasis of colorectal cancer frequently recurred in the peritoneum even after R0 resection. The cancer-specific survival of the single-organ metastasis in the peritoneum group was as poor as that of the multiple-organ metastases group. See Video Abstract at http://links.lww.com/DCR/A398.
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Li Q, Wang C, Li Y, Li X, Xu Y, Cai G, Lian P, Cai S. Lymph node status as a prognostic factor after palliative resection of primary tumor for patients with metastatic colorectal cancer. Oncotarget 2017; 8:48333-48342. [PMID: 28430643 PMCID: PMC5564651 DOI: 10.18632/oncotarget.15696] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 02/20/2017] [Indexed: 12/14/2022] Open
Abstract
Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database. X-tile program was adopted to identify 2 and 10 as optimal cutoff values for negative lymph node (NLN) count to divide patients into 3 subgroups of high, middle and low risk of cancer related death. N stage and NLN count were verified as independent prognostic factors in multivariate analyses of patients in whole cohort and in subgroup analyses of each N stage (P<0.05). Validation of FUSCC cohort of patients demonstrated that metastatic tumor burden (P = 0.042), NLN count (P = 0.039) and sequential chemotherapy (P = 0.040) were significant predictors of poorer CSS. Specifically, the prognosis of patients at stage N0 was significantly more favorable than that of patients at stage N2 (P = 0.038). In conclusion, primary tumor LN status was a strong predictor of CSS after palliative resection of metastatic colorectal cancer. Advanced N stage and small number of NLN were correlated with high risk of cancer related death after palliative resection of primary tumor.
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Affiliation(s)
- Qingguo Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Changjian Wang
- Anorectal Department, Hangzhou Third Hospital, Hangzhou, China
| | - Yaqi Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xinxiang Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Anorectal Department, Hangzhou Third Hospital, Hangzhou, China
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Guoxiang Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Peng Lian
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Ren H, Wang Z, Zhang S, Ma H, Wang Y, Jia L, Li Y. IL-17A Promotes the Migration and Invasiveness of Colorectal Cancer Cells Through NF-κB-Mediated MMP Expression. Oncol Res 2017; 23:249-56. [PMID: 27098148 PMCID: PMC7838743 DOI: 10.3727/096504016x14562725373716] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Interleukin-17A (IL-17A) plays a significant role in many inflammatory diseases and cancers. The aim of this study is to investigate the effect of IL-17A on the invasiveness of colorectal cancer. In the study, we found that IL-17A could promote the migration and invasion of colorectal cancer cells. Furthermore, after being treated with IL-17A, the expression and activity of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated. Moreover, the nuclear/overall fractions and DNA-binding activity of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with a nuclear factor-κB (NF-κB) inhibitor (PDTC) or PI3K/AKT inhibitor (LY294002) was proven to abolish the promoting effect of IL-17A on the invasion ability of colorectal cancer cells and upregulation of MMP-2/9. In conclusion, our findings demonstrated that IL-17A could promote the invasion of colorectal cancer cells by activating the PI3K/AKT/NF-κB signaling pathway and subsequently upregulating the expression of MMP-2/9. Our results suggest that IL-17A could serve as a promising therapeutic target for colorectal cancer.
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Affiliation(s)
- Hongtao Ren
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Samalavicius NE, Dulskas A, Baltruskeviciene E, Smailyte G, Skuciene M, Mikelenaite R, Venslovaite R, Aleknavicius E, Samalavicius A, Lunevicius R. Asymptomatic primary tumour in incurable metastatic colorectal cancer: is there a role for surgical resection prior to systematic therapy or not? Wideochir Inne Tech Maloinwazyjne 2016; 11:274-282. [PMID: 28194248 PMCID: PMC5299087 DOI: 10.5114/wiitm.2016.64981] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 12/18/2016] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION The role of the resection of asymptomatic primary colorectal cancer in patients with incurable disease is questionable. AIM To evaluate the impact of the resection of asymptomatic primary tumour on overall survival in patients with unresectable distant metastases. MATERIAL AND METHODS Patients treated in the National Cancer Institute, Lithuania, in the period 2008-2012, were selected retrospectively. The main inclusion criteria were: metastatic colorectal cancer (mCRC), endoscopically and histologically confirmed adenocarcinoma, without any symptoms for urgent operation, and at least one cycle of palliative chemotherapy administered. Information on patients' age, gender, tumour histology, localization of the tumour, regional lymph node involvement, number of metastatic sites, surgery and systemic treatment was collected prospectively. Eligible patients for the study were divided into two groups according to the initial treatment - surgery (patients who underwent primary tumour resection) and chemotherapy (patients who received chemotherapy without surgery). The impact of initial treatment strategy, tumour size and site, regional lymph nodes, grade of differentiation of adenocarcinoma and application of biotherapy on overall cumulative survival was estimated using the Kaplan-Meier method. To compare survival between groups the log-rank test was used. Cox regression analysis was employed to assess the effects of variables on patient survival. RESULTS The study group consisted of 183 patients: 103 men and 80 women. The median age was 66 years (range: 37-91). There were no notable imbalances with regard to age, gender, number of metastatic sites, metastases (such as pulmonary, peritoneal, liver, metastases into non-regional lymph nodes and other metastases), the number of received cycles of chemotherapy, first line chemotherapy type or biological therapy. Only 27 (14.8%) patients received biological therapy and the majority of them (n = 25, 92.6%) were treated with bevacizumab. For surgically treated patients 1-year survival was 71.2% (95% CI: 62.1-78.5) and 5-year survival was 4.0% (95% CI: 1.0-10.5). In the chemotherapy group, survival rates were lower - 43.9% (95% CI: 31.4-55.7) and 1.7% (95% CI: 0.1-8.1), respectively. Better survival rates were in the palliative surgery group. Multivariate analysis using the Cox proportional hazards model revealed that the initial palliative surgery and the application of biological therapy were statistically significant independent prognostic factors for survival. CONCLUSIONS Our findings suggest that palliative resectional surgery for the primary tumour in patients with incurable mCRC improves survival. Of course, one can argue that patients in the surgery group were "less problematic". Prospective randomized trials are needed to delineate precisely the role of palliative surgery of the primary tumour in these patients.
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Affiliation(s)
- Narimantas E. Samalavicius
- Center of Oncosurgery, National Cancer Institute, Clinic of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius, Lithuania
| | - Audrius Dulskas
- Center of Oncosurgery, National Cancer Institute, Vilnius, Lithuania
| | | | - Giedre Smailyte
- Centre of Cancer Control and Prevention, National Cancer Institute, Vilnius, Lithuania
| | - Marija Skuciene
- Center of Radiation and Medical Oncology, National Cancer Institute, Vilnius, Lithuania
| | | | - Rasa Venslovaite
- Center of Radiation and Medical Oncology, National Cancer Institute, Vilnius, Lithuania
| | - Eduardas Aleknavicius
- Center of Radiation and Medical Oncology, National Cancer Institute, Vilnius, Lithuania
| | - Almantas Samalavicius
- Department of Architectural Fundamentals and Theory, Vilnius Gediminas Technical University, Vilnius, Lithuania
| | - Raimundas Lunevicius
- General Surgery Department, Aintree University Hospital NHS Foundation Trust, University of Liverpool, Lower Lane, Liverpool, United Kingdom
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Huang CJ, Jiang JK, Chang SC, Lin JK, Yang SH. Serum CA125 concentration as a predictor of peritoneal dissemination of colorectal cancer in men and women. Medicine (Baltimore) 2016; 95:e5177. [PMID: 27893659 PMCID: PMC5134852 DOI: 10.1097/md.0000000000005177] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Peritoneal dissemination (PD) of cancer is difficult to diagnose. Previous reports have shown that carbohydrate antigen 125 (CA125) is a sensitive marker of PD of gastric cancer. However, CA125 has not been evaluated as a marker of colorectal cancer (CRC), and its accuracy in men is controversial. The aim of this study was to compare the ability of CA125 and carcinoembryonic antigen (CEA) to predict PD of CRC in men and women.Preoperative CA125 and CEA concentrations were measured in 853 people (510 men, 343 women) over 10 years. PD was confirmed intraoperatively in 57 patients. The predictive ability was compared between CA125 and CEA.Compared with CEA, CA125 concentration had a lower sensitivity, higher specificity, and diagnostic accuracy, and significantly greater area under the curve. Further analysis of CA125's sensitivity and specificity among CEA-negative group (n = 514) showed acceptable sensitivity (57.1%) and good specificity (92.0%). In men and women, CA125 concentration did not increase with stage from I to IV unless PD was present (P < 0.001). CEA concentration was increased in women with metastasis with PD (P < 0.001) or without PD (P < 0.001), but was increased only in men with metastasis without PD (P < 0.01). CA125 concentration correlated with PD grade for men and women, but CEA concentration correlated with grade only in women.When analyzed according to the primary tumor site, CA125 concentration in men did not differ between patients with the primary site in the right or left colon, or the rectum, regardless of PD status. By contrast, CA125 concentration differed between PD-positive and PD-negative patients with cancer in the right (P < 0.001) or left (P < 0.001) colon but not in the rectum. CEA concentration in men did not differ according to the primary site or PD status. In women, CA125 and CEA concentrations differed significantly between the PD-positive and PD-negative groups in patients with the primary tumor in the right (P < 0.001) or left (P < 0.001) colon; tumor sites did not differ between the PD-positive and PD-negative groups.These findings suggest that CA125 is a better tumor marker than CEA for predicting PD of CRC in both men and women.
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Affiliation(s)
- Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital and Department of Biochemistry, National Defense Medical Center
| | | | | | | | - Shung-Haur Yang
- Division of Colon and Rectal Surgery
- Division of Experimental Surgery, Department of Surgery, Taipei-Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
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28
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Jang HS, Ju JK, Kim CH, Lee SY, Kim HR, Kim YJ. Palliative resection of a primary tumor in patients with unresectable colorectal cancer: could resection type improve survival? Ann Surg Treat Res 2016; 91:172-177. [PMID: 27757394 PMCID: PMC5064227 DOI: 10.4174/astr.2016.91.4.172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 05/09/2016] [Accepted: 06/02/2016] [Indexed: 11/30/2022] Open
Abstract
PURPOSE The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC). METHODS A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined. RESULTS Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786). CONCLUSION Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002).
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Affiliation(s)
- Hyun Seok Jang
- Department of Surgery, Chonnam University Hospital, Gwangju, Korea
| | - Jae Kyun Ju
- Department of Surgery, Chonnam University Hospital, Gwangju, Korea
| | - Chang Hyun Kim
- Department of Surgery, Chonnam University Hwasun Hospital, Gwangju, Korea
| | - Soo Young Lee
- Department of Surgery, Chonnam University Hwasun Hospital, Gwangju, Korea
| | - Hyeong Rok Kim
- Department of Surgery, Chonnam University Hwasun Hospital, Gwangju, Korea
| | - Young Jin Kim
- Department of Surgery, Chonnam University Hwasun Hospital, Gwangju, Korea
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29
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Alawadi Z, Phatak UR, Hu CY, Bailey CE, You YN, Kao LS, Massarweh NN, Feig BW, Rodriguez-Bigas MA, Skibber JM, Chang GJ. Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer. Cancer 2016; 123:1124-1133. [PMID: 27479827 DOI: 10.1002/cncr.30230] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 05/27/2016] [Accepted: 06/27/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. METHODS An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. RESULTS In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). CONCLUSIONS Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.
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Affiliation(s)
- Zeinab Alawadi
- Department of General Surgery, The University of Texas Health Science Center, Houston Texas.,Center for Surgical Trials and Evidence-Based Practice, The University of Texas Health Science Center, Houston Texas
| | - Uma R Phatak
- Department of General Surgery, The University of Texas Health Science Center, Houston Texas.,Center for Surgical Trials and Evidence-Based Practice, The University of Texas Health Science Center, Houston Texas
| | - Chung-Yuan Hu
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas
| | - Christina E Bailey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas
| | - Y Nancy You
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas
| | - Lillian S Kao
- Department of General Surgery, The University of Texas Health Science Center, Houston Texas.,Center for Surgical Trials and Evidence-Based Practice, The University of Texas Health Science Center, Houston Texas
| | - Nader N Massarweh
- Department of Surgery, Division of Surgical Oncology, Baylor College of Medicine, Houston Texas
| | - Barry W Feig
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas
| | - Miguel A Rodriguez-Bigas
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas
| | - John M Skibber
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas
| | - George J Chang
- Center for Surgical Trials and Evidence-Based Practice, The University of Texas Health Science Center, Houston Texas.,Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas.,Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston Texas
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30
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Søreide K. Resection of asymptomatic primary tumour in unresectable stage IV colorectal cancer: time to move on from propensity matched scores to randomized controlled trials. Int J Cancer 2016; 139:1927-9. [PMID: 27400774 PMCID: PMC5095777 DOI: 10.1002/ijc.30244] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.,Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
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31
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Oncological benefit of lateral pelvic lymph node dissection for rectal cancer treated without preoperative chemoradiotherapy: a multicenter retrospective study using propensity score analysis. Int J Colorectal Dis 2016; 31:1315-21. [PMID: 27240821 DOI: 10.1007/s00384-016-2607-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/20/2016] [Indexed: 02/04/2023]
Abstract
PURPOSE We aimed to clarify the prognostic impact of lateral pelvic lymph node (LPN) dissection (LPND) for rectal cancer through a multicenter retrospective study using propensity score analysis. METHODS A total of 1238 patients with pathological T2-4, M0 rectal cancer who had undergone curative operation between 2007 and 2008 were examined. Majority of the patients (96 %) were treated without preoperative chemoradiotherapy (CRT). Clinical background data of the patients treated with LPND and those treated without LPND were matched using propensity scores, and hazard ratios (HRs) for cancer-specific mortality were compared. RESULTS LPND was performed more frequently for lower rectal cancers and in patients with more advanced disease, and 29 % of the patients were treated with LPND. After matching background features by propensity scores, LPND did not correlate with improved cancer-specific survival (CSS) among the entire study population [HR, 0.73; 95 % confidence interval (CI) 0.41-1.31; P = 0.28]; however, LPND was correlated with significantly improved CSS in female patients (HR, 0.23; 95 % CI, 0.06-0.89; P = 0.04) but not in male patients (HR, 0.95; 95 % CI, 0.48-1.89; P = 0.89). The results were similar when patients treated with LPND finally diagnosed as pathologically negative for LPN metastasis were compared with those curatively treated without LPND. CONCLUSIONS It is suggested that the prognostic impact of LPND for rectal cancer treated without CRT might be different between sexes, and LPND should be considered for female rectal cancer patients although they are diagnosed as clinically negative for LPN metastasis.
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32
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Shida D, Hamaguchi T, Ochiai H, Tsukamoto S, Takashima A, Boku N, Kanemitsu Y. Prognostic Impact of Palliative Primary Tumor Resection for Unresectable Stage 4 Colorectal Cancer: Using a Propensity Score Analysis. Ann Surg Oncol 2016; 23:3602-3608. [DOI: 10.1245/s10434-016-5299-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Indexed: 12/15/2022]
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Prognostic impact of lymph node dissection is different for male and female colon cancer patients: a propensity score analysis in a multicenter retrospective study. Int J Colorectal Dis 2016; 31:1149-55. [PMID: 27023629 DOI: 10.1007/s00384-016-2558-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/02/2016] [Indexed: 02/04/2023]
Abstract
PURPOSE Colon cancers in male and female patients are suggested to be oncologically different. The aim of this study is to elucidate the prognostic impact of lymph node dissection (LND) in male and female colon cancer patients. METHODS A total of 5941 stage I-III colon cancer patients who were curatively operated on during the period from 1997 to 2007 were retrospectively studied. Cancer-specific survival (CSS) was individually compared between for male and female patients treated with D3, D2, and D1 LND. Background differences of the patients were matched using propensity scores. RESULTS D3, D2, and D1 LND were performed in 3756 (63 %), 1707 (29 %), and 478 (8 %), respectively, and more extensive LND was indicated for younger patients and more advanced disease. D2 LND was significantly associated with decreased cancer-specific mortality compared to D1 LND in male patients (HR 0.54, 95 % CI 0.32-0.89, p = 0.04), but not in female patients. D3 LND did not correlate to an improved prognosis compared to D2 LND both in male and female patients. CONCLUSIONS D2 LND was associated with an improved CSS in male, but not female colon cancer patients, compared to D1 LND. This suggested that colon cancer in male and female patients might be oncologically different, and that the prognostic impact of the extent of surgical intervention for colon cancer might therefore be different between sexes.
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Li ZM, Peng YF, Du CZ, Gu J. Colon cancer with unresectable synchronous metastases: the AAAP scoring system for predicting the outcome after primary tumour resection. Colorectal Dis 2016; 18:255-263. [PMID: 26400111 DOI: 10.1111/codi.13123] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 07/05/2015] [Indexed: 12/22/2022]
Abstract
AIM The aim of this study was to develop a prognostic scoring system to predict the outcome of patients with unresectable metastatic colon cancer who received primary colon tumour resection. METHOD Patients with confirmed metastatic colon cancer treated at the Peking University Cancer Hospital between 2003 and 2012 were reviewed retrospectively. The correlation of clinicopathological factors with overall survival was analysed using the Kaplan-Meier method and the log-rank test. Independent prognostic factors were identified using a Cox proportional hazards regression model and were then combined to form a prognostic scoring system. RESULTS A total of 110 eligible patients were included in the study. The median survival time was 10.4 months and the 2-year overall survival (OS) rate was 21.8%. Age over 70 years, an alkaline phosphatase (ALP) level over 160 IU/l, ascites, a platelet/lymphocyte ratio (PLR) above 162 and no postoperative therapy were independently associated with a shorter OS in multivariate analysis. Age, ALP, ascites and PLR were subsequently combined to form the so-called AAAP scoring system. Patients were classified into high, medium and low risk groups according to the score obtained. There were significant differences in OS between each group (P < 0.001). CONCLUSION Age, ALP, ascites, PLR and postoperative therapy were independent prognostic factors for survival of patients with metastatic colonic cancer who underwent primary tumour resection. The AAAP scoring system may be a useful tool for surgical decision making.
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Affiliation(s)
- Z M Li
- Department of Colorectal Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Y F Peng
- Department of Colorectal Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - C Z Du
- Department of Colorectal Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - J Gu
- Department of Colorectal Surgery, Peking University Cancer Hospital and Institute, Beijing, China
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35
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Shibata J, Kawai K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Sugihara K, Watanabe T. Prognostic Impact of Histologic Type in Curatively Resected Stage IV Colorectal Cancer: A Japanese Multicenter Retrospective Study. Ann Surg Oncol 2015; 22 Suppl 3:S621-9. [DOI: 10.1245/s10434-015-4846-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Indexed: 12/21/2022]
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Zhang W, He J, Du Y, Gao XH, Liu Y, Liu QZ, Chang WJ, Cao GW, Fu CG. Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer. World J Gastroenterol 2015; 21:8836-8847. [PMID: 26269673 PMCID: PMC4528026 DOI: 10.3748/wjg.v21.i29.8836] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2015] [Revised: 02/14/2015] [Accepted: 03/27/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer.
METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer.
RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells.
CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis.
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37
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Benefit of primary tumor resection in stage IV colorectal cancer with unresectable metastasis: a multicenter retrospective study using a propensity score analysis. Int J Colorectal Dis 2015; 30:807-12. [PMID: 25922146 DOI: 10.1007/s00384-015-2228-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/21/2015] [Indexed: 02/08/2023]
Abstract
PURPOSE Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer (CRC) with unresectable metastasis (mCRC). The aim of this study was to investigate the prognostic impact of primary tumor resection in various subgroups of mCRC patients. METHODS A total of 1982 patients with mCRC from January 1997 to December 2007 were retrospectively evaluated. The impact of primary tumor resection on cancer-specific survival (CSS) was analyzed using propensity score analysis to mitigate selection bias. Covariates in the models for propensity scores included treatment period, age, gender, tumor location, depth, lymph node metastasis, number of metastatic organs, and carcinoembryonic antigen (CEA) levels. RESULTS Among the whole patient population, primary tumor resection significantly improved CSS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.32-0.66, p < 0.01]. However, primary tumor resection did not significantly improve CSS in the following subgroups: patients treated in the first 5 years of the study (HR 0.56, 95% CI 0.28-1.13, p = 0.08), patients aged >65 years (HR 0.72, 95% CI 0.36-1.42, p = 0.31), female patients (HR 0.60, 95% CI 0.31-1.17, p = 0.13), patients with right-sided colon cancer (HR 0.68, 95% CI 0.39-1.20, p = 0.17), and patients without nodal involvement (HR 0.54, 95% CI 0.25-1.17, p = 0.09). CONCLUSIONS Our study suggests that primary tumor resection improves the survival of patients with mCRC. However, the prognostic benefit is different among patient subpopulations.
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Furuhata T, Okita K, Nishidate T, Hirata K, Ohnishi H, Kobayashi H, Kotake K, Sugihara K. Oncological benefit of primary tumor resection with high tie lymph node dissection in unresectable colorectal cancer with synchronous peritoneal metastasis: a propensity score analysis of data from a multi-institute database. Int J Clin Oncol 2015; 20:922-7. [PMID: 25762168 DOI: 10.1007/s10147-015-0815-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 03/01/2015] [Indexed: 01/07/2023]
Abstract
BACKGROUND Peritoneal metastasis is recognized as a predictor of poor prognosis in patients with colorectal cancer, and whether surgical intervention for peritoneal metastasis has any clinical benefit has remained controversial. The purposes of this study were to identify prognostic factors in cases of unresectable colorectal cancer with synchronous peritoneal metastasis and to clarify the impacts of primary tumor resection with high tie lymph node dissection. METHODS A multi-institutional retrospective analysis was conducted of 579 patients who underwent resection of the primary tumor for unresectable colorectal cancer with peritoneal metastasis between 1991 and 2007. For these 579 patients, clinicopathological variables were analyzed for prognostic significance using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. RESULTS Multivariate analysis revealed hematogenous metastasis (p < 0.001), histology of the tumor (p = 0.006), postoperative chemotherapy (p < 0.001), and lymph node dissection (p = 0.001) as independent prognostic factors. In the propensity-matched cohort, patients treated with high tie lymph node dissection showed a significantly better overall survival than those with low tie lymph node dissection (median overall survival 13.0 vs. 11.5 months; p = 0.041). CONCLUSIONS It is suggested that primary tumor resection with high tie lymph node dissection favorably affects survival, even in unresectable colorectal cancer with peritoneal metastasis.
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Affiliation(s)
- Tomohisa Furuhata
- Department of Nursing, Sapporo Medical University, South 1, West 17, Chuo-ku, Sapporo, Japan.
| | - Kenji Okita
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Toshihiko Nishidate
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Koichi Hirata
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Hirofumi Ohnishi
- Department of Public Health, Sapporo Medical University, Sapporo, Japan
| | - Hirotoshi Kobayashi
- Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kenjiro Kotake
- Department of Surgery, Tochigi Cancer Center, Utsunomiya, Japan
| | - Kenichi Sugihara
- Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan
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Ozawa T, Ishihara S, Sunami E, Kitayama J, Watanabe T. Log odds of positive lymph nodes as a prognostic indicator in stage IV colorectal cancer patients undergoing curative resection. J Surg Oncol 2015; 111:465-71. [PMID: 25690280 DOI: 10.1002/jso.23855] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 11/08/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recent studies have proposed the use of log odds of positive lymph nodes (LODDS) as a prognostic indicator in colorectal cancer (CRC) patients without distant synchronous metastasis. In the present study, we aimed to evaluate the prognostic impact of the LODDS in Stage IV CRC patients who have undergone curative resection. METHODS We performed a retrospective review of 117 Stage IV CRC patients who underwent curative resection at our institute from 1998 to 2011. Patients were categorized into 3 groups (LODDS1-3) according to the ratio of their LODDS. The relationship between the LODDS and disease-free survival (DFS) and overall survival (OS) rates were assessed. RESULTS DFS was not significantly different between patients in each LODDS group. The association between the LODDS classification and OS was statistically significant (P = 0.021). Multivariate analysis indicated that LODDS classification was an independent prognostic factor for OS, with a hazard ratio of 2.95 for LODDS2 (95% confidence interval [CI]: 1.18-8.35; P = 0.021), and 2.98 for LODDS3 (95% CI: 1.20-8.37; P = 0.017). CONCLUSIONS The LODDS is a good prognostic indicator in Stage IV CRC patients who have undergone curative resection.
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Affiliation(s)
- Tsuyoshi Ozawa
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Cotte E, Villeneuve L, Passot G, Boschetti G, Bin-Dorel S, Francois Y, Glehen O, The French Research Group of Rectal Cancer Surgery (GRECCAR). GRECCAR 8: impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis: a randomized multicentre study. BMC Cancer 2015; 15:47. [PMID: 25849254 PMCID: PMC4327953 DOI: 10.1186/s12885-015-1060-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Accepted: 01/29/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND A majority of patients with rectal cancer and metastasis are not eligible to curative treatment because of an extensive and unresectable metastatic disease. Primary tumor resection is still debated in this situation. Rectal surgery treats or prevents the symptoms and avoids the risk of acute complications related to the primary tumor. Several studies on colorectal cancers seem to show interesting results in terms of survival in favor to the resection of the primary tumor. To date, no randomized trial or even a prospective study has assessed the impact of primary tumor resection on overall survival in patients with colorectal cancer with unresectable metastasis. All published studies were retrospective and included colon and rectal cancers. Rectal cancer is associated with specific problems related to the rectal surgery. Surgery is more complex, and may be source of more morbidity and postoperative functional dysfunctions (stoma, digestive, sexual, urinary) than colic surgery. On the other hand, symptoms related to the progression of rectal tumor are often very disabling: pain, rectal syndrome. METHODS/DESIGN GRECCAR 8 is a multicentre randomized open-label controlled trial aimed to evaluate the impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis. Patients must undergo upfront systemic chemotherapy for at least 4 courses before inclusion. Patients with progressive metastatic disease during upfront chemotherapy will be excluded from the study. Patients will be randomly assigned in a 1:1 ratio to Arm A: primary tumor resection followed by systemic chemotherapy versus Arm B: systemic chemotherapy alone. Primary endpoint will be overall survival measured from the date of randomization to the date of death or to the end of follow-up (2 years). Secondary endpoints will include progression-free survival, quality of life, toxicity of chemotherapy, response of the primary tumor and metastatic disease to chemotherapy, postoperative morbidity and mortality, rate of patient not eligible for postoperative chemotherapy (arm A), primary tumor related complications and rate of emergency surgery (arm B). The number of patients needed is 290. TRIAL REGISTRATION ClinicalTrial.gov: NCT02314182.
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Affiliation(s)
- Eddy Cotte
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
- Université Lyon 1, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | - Laurent Villeneuve
- Université Lyon 1, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
- Hospices Civils de Lyon, Unité de Recherche Clinique, Pôle IMER, Lyon, France
| | - Guillaume Passot
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
- Université Lyon 1, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | - Gilles Boschetti
- Department of Gastroenterology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Sylvie Bin-Dorel
- Hospices Civils de Lyon, Unité de Recherche Clinique, Pôle IMER, Lyon, France
| | - Yves Francois
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
- Université Lyon 1, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | - Olivier Glehen
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
- Université Lyon 1, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | - The French Research Group of Rectal Cancer Surgery (GRECCAR)
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
- Université Lyon 1, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
- Hospices Civils de Lyon, Unité de Recherche Clinique, Pôle IMER, Lyon, France
- Department of Gastroenterology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
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