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Yang Y, Yang Z, Lyu Z, Wang J, Wu D, Li Y. Predicting Surgical Benefit for Primary Tumor Resection in Patients with Stage IV Colorectal Cancer.. [DOI: 10.21203/rs.3.rs-2031087/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Abstract
Purpose
There exists continuous controversy regarding the effect of primary tumor resection (PTR) for stage IV colorectal cancer (CRC) patients. Little is known about how to predict the patients’ survival benefit from PTR. This study aimed to develop a tool for surgical benefit prediction.
Methods
Stage IV CRC patients diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results database were included. After propensity score matching, patients receiving PTR that survived longer than the median cancer-specific survival (CSS) time of those who did not undergo PTR were considered to benefit from surgery. Logistic regression analysis identified prognostic factors influencing the surgical benefit, based on which a nomogram was constructed. A user-friendly webserver was then built for convenient clinical use. The predictive model was assessed using Harrell’s concordance index, calibration plot, receiver operative curve and decision curve analysis.
Results
The median CSS of the PTR group was 23 months, which was significantly longer than the non-PTR group (12 months, P < 0.001). In the PTR group, 32.9% of patients did not benefit from surgery. Logistic regression analysis identified age, tumor location, CEA level, histological grade, number of distant metastasis, and preoperative chemotherapy independently associated with surgical benefit. The established prognostic nomogram demonstrated satisfactory performance.
Conclusion
PTR was associated with prolonged survival in stage IV CRC. The proposed nomogram could be used as a risk-to-benefit assessment evidenced-based platform for selecting appropriate patients to undergo PTR.
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Affiliation(s)
| | | | | | | | - Deqing Wu
- Guangdong Provincial People's Hospital
| | - Yong Li
- Guangdong Provincial People's Hospital
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Shu Y, Xu L, Yang W, Xu X, Zheng S. Asymptomatic Primary Tumor Resection in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:836404. [PMID: 35425714 PMCID: PMC9001954 DOI: 10.3389/fonc.2022.836404] [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: 12/15/2021] [Accepted: 03/07/2022] [Indexed: 11/18/2022] Open
Abstract
Background In patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor. Methods The PubMed, Embase and the Cochrane Library databases were searched from inception to November 30,2021. A meta-analysis was performed using RevMan (version 5.3.3; The Cochrane Collaboration) on the outcome of mCRC patients with or without resection of the primary tumor in 8 selected studies. Results This meta-analysis included 2805 colorectal cancer patients with an asymptomatic primary tumor from 8 selected studies. Primary tumor resection (PTR) patients had longer overall survival (OS: MD =6.76 [3.39, 10.12], I2 = 77%, P < 0.0001), compared with non-primary tumor resection (NPTR) patients. In the subgroup, the randomized controlled trials (RCT) PTR group didn’t have longer overall survival (OS: MD =3.79 [-3.49, 11.08], I2 = 69%, P= 0.31); the Non-RCT PTR group had longer overall survival (OS: MD =8.42 [3.14, 13.70], I2 = 89%, P= 0.002). In the meanwhile, compared with NPTR group, the 2-year overall survival rate, the 3-year overall survival rate, 5-year overall survival rate in the PTR group is higher (OR=2.35 [1.74, 3.18], I2 = 0%, P < 0.00001; OR=3.61 [2.35, 5.54], I2 = 0%, P < 0.00001; OR=3.02 [1.72, 5.33], I2 = 48%, P= 0.0001, respectively). Conclusions Our results from studies demonstrate that the resection of primary tumor is a prognostic factor for survival in mCRC patients. However, 2 RCTs showed the resection of primary tumor was not related with a significant survival benefit in subgroup. Therefore, a larger RCT in the era of modern chemotherapy and liver resection techniques would be helpful.
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Affiliation(s)
- Yefei Shu
- Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China
| | - Ling Xu
- Department of Oncology and Hematology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Wei Yang
- Department of Oncology and Hematology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Xiaofeng Xu
- Department of Oncology and Hematology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Song Zheng
- Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China.,Department of Medical Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Huang M, Yang Y, Li Q, Wang C, Liang L, Zhu X, Zhang W, Chen Z, Huang D, Li W, Zhang X, Zhao X, Qiu L, Geng Q, Yu N, Du W, Sun S, Sheng X, Li X, Guo W. Induction Chemotherapy Followed by Primary Tumor Resection Did Not Bring Survival Benefits in Colon Cancer Patients With Asymptomatic Primary Lesion and Synchronous Unresectable Metastases. Front Oncol 2022; 12:747124. [PMID: 35174078 PMCID: PMC8841852 DOI: 10.3389/fonc.2022.747124] [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] [Received: 07/25/2021] [Accepted: 01/04/2022] [Indexed: 12/24/2022] Open
Abstract
BackgroundIt is still controversial whether primary tumor resection (PTR) improves survival in colorectal cancer (CRC) patients with unresectable metastases.MethodsColon cancer patients were enrolled and randomly allocated to with or without PTR after induction chemotherapy with XELOX or mFOLFOX6, and those with chemotherapy failure were excluded. The primary endpoint was TTF (time to strategy failure) on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02291744.ResultsBetween April 2015 and July 2020, 140 patients were enrolled, and 54 patients were excluded due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). After induction chemotherapy, 86 patients were randomized into group A (the resection group, n = 42) or group B (chemotherapy-alone group, n = 44). The median TTF was 143 days (95% CI: 104.9–181.1) in group A and 196 days (95% CI: 96.5–295.5) in group B (HR: 0.930 95% CI: 0.589–1.468, p = 0.755), and there was no significant difference in PFS, OS, and incidence of chemotherapy-related adverse events between two groups. The primary lesion-related events after PTR in group A were significantly fewer than those in group B. Patients with a tumor regression grade (TRG) score of 2 had longer TTF and PFS than those with score of 3.ConclusionPTR after induction chemotherapy could not bring survival benefits for colon cancer patients with unresectable metastases, and it is not recommended routinely. However, it also requires individualized treatment as colon obstruction or perforation occurred in some patients and PTR could reduce primary tumor-related events, and the TRG score might help for selection of beneficial patients.
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Affiliation(s)
- Mingzhu Huang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ya’nan Yang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qingguo Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Chenchen Wang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Liang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaodong Zhu
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen Zhang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiyu Chen
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dan Huang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Wenhua Li
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaowei Zhang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaoying Zhao
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lixin Qiu
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qirong Geng
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Nuoya Yu
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenfang Du
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sijie Sun
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xuedan Sheng
- Department of Gastrointestinal Medical Oncology, 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
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- *Correspondence: Weijian Guo, ; Xinxiang Li,
| | - Weijian Guo
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- *Correspondence: Weijian Guo, ; Xinxiang Li,
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Liang Z, Liu Z, Huang C, Chen X, Zhang Z, Xiang M, Hu W, Wang J, Feng X, Yao X. The role of upfront primary tumor resection in asymptomatic patients with unresectable stage IV colorectal cancer: A systematic review and meta-analysis. Front Surg 2022; 9:1047373. [PMID: 36684350 PMCID: PMC9857770 DOI: 10.3389/fsurg.2022.1047373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/01/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Controversy exists over the role of upfront primary tumor resection (PTR) in asymptomatic patients with unresectable stage IV colorectal cancer (CRC). The purpose of this study was to evaluate the effect of upfront PTR on survival outcomes and adverse outcomes. METHODS Searches were conducted on PubMed, EMBASE, Web of Science, and Cochrane Library from inception to August 2021. Studies comparing survival outcomes with or without adverse outcomes between PTR and non-PTR treatments were included. Review Manager 5.3 was applied for meta-analyses with a random-effects model whenever possible. RESULTS Overall, 20 studies with 3,088 patients were finally included in this systematic review. Compared with non-PTR, upfront PTR was associated with better 3-year (HR: 0.69, 95% CI, 0.57-0.83, P = 0.0001) and 5-year overall survival (OS) (HR: 0.77, 95% CI, 0.62-0.95, P = 0.01), while subgroup analysis indicated that there was no significant difference between upfront PTR and upfront chemotherapy (CT) group. In addition, grade 3 or higher adverse effects due to CT were more frequent in the PTR group with marginal significance (OR: 1.74, 95% CI, 0.99-3.06, P = 0.05), and other adverse outcomes were comparable. CONCLUSIONS PTR might be related to improved OS for asymptomatic patients with unresectable stage IV CRC, whereas receiving upfront CT is a rational alternative without detrimental influence on survival or adverse outcomes compared with upfront PTR. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272675.
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Affiliation(s)
- Zongyu Liang
- Department of Gastrointestinal Surgery, Second Department of General Surgery, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
| | - Zhiyuan Liu
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
| | - Chengzhi Huang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Xin Chen
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
| | - Zhaojun Zhang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Meijuan Xiang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Weixian Hu
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Junjiang Wang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- School of Medicine, South China University of Technology, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xingyu Feng
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Correspondence: Xingyu Feng ; Xueqing Yao
| | - Xueqing Yao
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Correspondence: Xingyu Feng ; Xueqing Yao
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Yoshida Y, Aisu N, Kojima D, Mera T, Kiyomi F, Yamashita Y, Hasegawa S. Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02). Ann Gastroenterol Surg 2017; 1:219-225. [PMID: 29863132 PMCID: PMC5881310 DOI: 10.1002/ags3.12023] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 06/04/2017] [Indexed: 12/14/2022] Open
Abstract
Initiating chemotherapy usually requires a delay of more than 4 weeks after surgically resecting colorectal cancer. However, there is little evidence regarding the required delay interval. We have previously reported a pilot study to determine the safety and feasibility of early initiation of chemotherapy after resecting primary colorectal cancer with distant metastases. We aimed to determine the safety and efficacy of early initiation of chemotherapy after resecting colorectal cancer with distant metastases. This phase II study (trial number UMIN000006310) was a prospective, single-arm trial. A total of 20 patients (men, 15 and women, 5) were enrolled. They underwent XELOX therapy (130 mg/m2 oxaliplatin on day 1+1000 mg/m2 capecitabine twice daily on days 1-4) on postoperative day 7 and XELOX+bevacizumab (7.5 mg/kg bevacizumab on day 1) after the second chemotherapy cycle. Baseline characteristics included a median age of 64 (range, 43-72) years. Surgical procedures included right hemicolectomy in six patients, sigmoidectomy in three, anterior resection in five, and Hartmann procedure in six. All patients started chemotherapy on postoperative day 7. Median progression-free survival was 14.9 months; overall response rate was 80%. Disease control rate was 100%. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 5.0% and 25.0% of patients, respectively. Postoperative complications were observed in two patients (superficial incisional surgical site infection and ileus). Early initiation of chemotherapy after surgery is feasible. These findings suggest future changes of the start time of chemotherapy after surgery.
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Affiliation(s)
- Yoichiro Yoshida
- Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan
| | - Naoya Aisu
- Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan
| | - Daibo Kojima
- Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan
| | - Toshiyuki Mera
- Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan
| | - Fumiaki Kiyomi
- Academia Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation Fukuoka University Fukuoka Japan
| | - Yuichi Yamashita
- Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan
| | - Suguru Hasegawa
- Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan
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Ha GW, Kim JH, Lee MR. Meta-analysis of oncologic effect of primary tumor resection in patients with unresectable stage IV colorectal cancer in the era of modern systemic chemotherapy. Ann Surg Treat Res 2017; 95:64-72. [PMID: 30079322 PMCID: PMC6073043 DOI: 10.4174/astr.2018.95.2.64] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 12/27/2017] [Accepted: 01/04/2018] [Indexed: 12/22/2022] Open
Abstract
Purpose The management of primary tumors in patients with stage IV colorectal cancer remains unclear. This meta-analysis evaluated the survival benefits of primary tumor resection (PTR) in patients with unresectable stage IV colorectal cancer in the era of modern chemotherapy. Methods Multiple comprehensive databases were searched for studies comparing survival outcomes in patients with metastatic colorectal cancer who did and did not undergo PTR. Outcome data were pooled, and overall effect size was calculated using random effect models. Results Seventeen nonrandomized studies involving 18,863 patients met the inclusion criteria. Meta-analysis showed that PTR significantly improved overall survival (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.56–0.71; P < 0.001) and progression free survival (HR, 0.76; 95% CI, 0.67–0.87; P < 0.001). Subgroup analyses and sensitivity analyses, performed by predefined methods, also indicated that PTR improved overall patient survival. Conclusion Palliative resection of the primary tumor may have survival benefits in patients with unresectable stage IV colorectal cancer. Randomized controlled trials are needed to determine the optimal treatment for these patients.
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Affiliation(s)
- Gi Won Ha
- Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Jong Hun Kim
- Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Min Ro Lee
- Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
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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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Lee KC, Ou YC, Hu WH, Liu CC, Chen HH. Meta-analysis of outcomes of patients with stage IV colorectal cancer managed with chemotherapy/radiochemotherapy with and without primary tumor resection. Onco Targets Ther 2016; 9:7059-7069. [PMID: 27895498 PMCID: PMC5117884 DOI: 10.2147/ott.s112965] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background Colorectal cancer is the third leading cause of death worldwide. Currently, novel chemotherapeutic agents are first-line therapy for unresectable stage IV colorectal cancer, while benefits of noncurative primary tumor resection in advanced disease remain debatable. Objective This meta-analysis evaluated outcomes of patients with unresectable stage IV colorectal cancer receiving systemic chemotherapy with or without primary tumor resection. Materials and methods A database search of PubMed and Cochrane Library databases identified 167 studies that were screened for relevance. After 119 were excluded, 48 were assessed for eligibility and 26 were included for meta-analysis, including 24 retrospective studies, one prospective study, and one randomized, controlled trial. Extracted data included patient demographics (age, sex), clinical data (tumor stage, metastasis), targeted therapy agents, and surgical data (with/without tumor resection). Patients’ overall and progression-free survival was compared between groups with/without primary tumor resection. Results The 26 studies included 43,903 patients with colorectal cancer, with 29,639 receiving chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed medically with chemotherapy/chemoradiotherapy alone without primary tumor resection. Patients receiving primary tumor resection plus chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51–0.68; P<0.001), with significant differences in overall survival between patients with and without primary tumor resection (HR 0.58, 95% CI 0.49–0.68; P<0.001). Longer overall survival was also found among patients receiving primary tumor resection who were treated with bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46–0.86; P=0.003). Patients from three studies who received primary tumor resection had longer progression-free survival (HR 0.73, 95% CI 0.58–0.91; P=0.005). Results are limited by retrospective data, inconsistent complications data, and publication bias. Conclusion Study results support primary tumor resection in stage IV colorectal cancer, but significant biases in studies suggest that randomized trials are warranted to confirm findings.
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Affiliation(s)
- Ko-Chao Lee
- Division of Colorectal Surgery, Department of Surgery
| | - Yu-Che Ou
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung
| | - Wan-Hsiang Hu
- Division of Colorectal Surgery, Department of Surgery
| | - Chia-Cheng Liu
- Department of Surgery, Pingtung Christian Hospital, Pingtung, Taiwan
| | - Hong-Hwa Chen
- Division of Colorectal Surgery, Department of Surgery
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Wilkinson KJ, Chua W, Ng W, Roohullah A. Management of asymptomatic primary tumours in stage IV colorectal cancer: Review of outcomes. World J Gastrointest Oncol 2015; 7:513-523. [PMID: 26691885 PMCID: PMC4678398 DOI: 10.4251/wjgo.v7.i12.513] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 09/23/2015] [Accepted: 11/04/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To compare outcomes for patients presenting with stage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection (PTR) plus palliative chemotherapy vs primary chemotherapy up-front.
METHODS: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort.
RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primary-tumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1b stage and non-use of modern chemotherapy agents.
CONCLUSION: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated.
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