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Bunjo Z, Sammour T. The Landmark Series: Neoadjuvant Therapy for Locally Advanced Rectal Cancer. Ann Surg Oncol 2025:10.1245/s10434-025-17299-5. [PMID: 40263223 DOI: 10.1245/s10434-025-17299-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 03/22/2025] [Indexed: 04/24/2025]
Abstract
The management of locally advanced rectal cancer (LARC) has seen much development over recent decades. Neoadjuvant radiotherapy combined with high-quality total mesorectal excision saw improvements in locoregional control. With the advent of several key trials, neoadjuvant therapy for LARC has seen a shift toward total neoadjuvant therapy, with corresponding improvements in tumor response and survival outcomes. The collective pool of evidence has allowed for increasingly personalized treatment of LARC, with organ-preservation now an option for many. The aims of the review are to summarize the evolution of neoadjuvant therapy for LARC, highlight key studies informing contemporary best practices, navigate the complexity of options available, and present areas of ongoing development.
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Affiliation(s)
- Zachary Bunjo
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia
- Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - Tarik Sammour
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia.
- Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
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Baig M, Sayyed R, Nasim S, Khan S. Effect of rectal washout on local recurrence of rectal cancer in the era of total mesorectal excision: Meta-analysis. Surgeon 2021; 19:351-355. [PMID: 33583687 DOI: 10.1016/j.surge.2020.11.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 11/11/2020] [Accepted: 11/27/2020] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Presence of intraluminal viable cancer cells implanting into the anastomosis has been proposed as a potential cause for developing local recurrence in patients undergoing anterior resection for rectal cancer. Rectal washout has been proposed as a method to prevent this from happening. There have been conflicting reports in literature regarding the effect of rectal washout on local recurrence. We aim to look at the role of rectal washout in preventing local recurrence of rectal cancer in patients undergoing total or tumor-specific mesorectal excision (TME). MATERIALS AND METHODS A literature review of studies evaluating the role of rectal washout on rectal cancer local recurrence was performed using PubMed, Scopus, EMBASE and non-English language literature search using CiNii (Japanese) and CNKI (Chinese). Inclusion criteria were use of TME, comparison of rectal washout with no washout, and evaluation of local recurrence as outcome. RESULTS Four studies were identified according to inclusion criteria. The meta-analysis showed a protective effect of rectal washout on local recurrence (OR 0.45 95% CI 0.45-0.75). However, one of the studies included had more than 90% weightage. Excluding this study from analysis showed no difference on local recurrence with rectal washout (OR 0.94, 95% CI 0.37-2.36). CONCLUSION The effect of rectal washout on rectal cancer local recurrence in patients who undergo TME is questionable and needs to be evaluated further by prospective studies.
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Affiliation(s)
- Mariam Baig
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital & Research Center, 7-A, Block R3, Johar Town, Lahore, Pakistan.
| | - Raza Sayyed
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital & Research Center, 7-A, Block R3, Johar Town, Lahore, Pakistan
| | - Sana Nasim
- Department of Surgery, The Aga Khan University Hospital, National Stadium Road, Karachi, Sindh, Pakistan
| | - Sadaf Khan
- Department of Surgery, The Aga Khan University Hospital, National Stadium Road, Karachi, Sindh, Pakistan
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Sanford NN, Aguilera TA, Beg MS, Sanjeevaiah A, Hong TS, Wo JY, Folkert MR. Patterns of Care for Stage II-III Rectosigmoid Cancers in the United States, 2004-2015. Am J Clin Oncol 2020; 43:311-318. [DOI: 10.1097/coc.0000000000000674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Lee JL, Lim SB, Yu CS, Park IJ, Yoon YS, Kim CW, Park SH, Lee JS, Hong YS, Kim SY, Kim JE, Kim JH, Park JH, Kim J, Han M. Local excision in mid-to-low rectal cancer patients who revealed clinically total or near-total regression after preoperative chemoradiotherapy; a proposed trial. BMC Cancer 2019; 19:404. [PMID: 31035949 PMCID: PMC6489182 DOI: 10.1186/s12885-019-5581-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 04/04/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is currently a standard therapy for locally advanced mid-to-low rectal cancer. Less aggressive, organ-preserving option such as local excision (LE) or watchful wait can alternatively be used for patients who respond well to pre-CRT. High-resolution rectal magnetic resonance imaging (MRI) is one of the most useful methods to assess pre-CRT response, and the MERCURY group has shown that the MR tumor regression grade (mrTRG) correlated with the pathologic TRG. The aim of this study is to compare postoperative complication and oncologic outcomes between LE and TME in mid-to-low rectal cancer patients whose tumors are mrTRG grade 1 (radiological complete remission) or 2 (predominant fibrosis; near-complete remission) after pre-CRT. METHODS A prospective, double-arm, randomized, open-labeled, single center, clinical trial will be conducted in patients with mid-to-low rectal cancer whose tumors are mrTRG 1/2 after pre-CRT at the Asan Medical Center, Seoul, Korea, after approval from the Institution Review Board. Patient medical records will be de-identified using a serial number to protect personal information. Inclusion criteria will include rectal adenocarcinoma with an inferior border < 8 cm from the anal verge, mrTRG 1/2, age > 20, and provision of informed consent. Postoperative complications will be assessed by Clavien-Dindo Classification Grade. Oncologic and functional outcomes will be collected and risk factors related to these outcomes will be investigated. DISCUSSION We believed that the rate of postoperative complication of LE will be comparable to that of TME in mid-to-low advanced rectal cancer patients with a favorable response after pre-CRT. TRIAL REGISTRATION KCT0002579 ( https://cris.nih.go.kr ) Dec-2017.
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Affiliation(s)
- Jong Lyul Lee
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Seok-Byung Lim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Chang Sik Yu
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Chan Wook Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Seong Ho Park
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Jong Seok Lee
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Yong Sang Hong
- Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Sun Young Kim
- Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Jeong Eun Kim
- Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Jin-hong Park
- Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Jihun Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
| | - Minkyu Han
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea
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Prediction of lateral pelvic lymph node metastasis in patients with locally advanced rectal cancer with preoperative chemoradiotherapy: Focus on MR imaging findings. PLoS One 2018; 13:e0195815. [PMID: 29649321 PMCID: PMC5897011 DOI: 10.1371/journal.pone.0195815] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 03/31/2018] [Indexed: 01/11/2023] Open
Abstract
PURPOSE To investigate the predictive factors for lateral pelvic lymph node (LPLN) metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS Fifty-seven patients with locally advanced rectal cancer and LPLNs larger than 5 mm underwent LPLN dissection (LPLD) after preoperative CRT. The MRI findings, including the apparent diffusion coefficient value and LPLN size reduction rate before/after CRT; clinical factors; and pathologic results were evaluated to identify the predictive factors associated with LPLN metastasis. RESULTS LPLN metastasis was confirmed in 23 patients (40.4%). Metastasis was significantly higher in LPLNs with multiplicity, short-axis diameter ≥8 mm before CRT, short-axis diameter >5 mm after CRT, size reduction rate ≤33.3%, heterogeneous signal intensity, and irregular margin (P<0.05) on MR. Multivariable analysis showed that pre-CRT short-axis diameter of LPLNs ≥8 mm, size reduction rate ≤33.3%, and heterogeneous signal intensity were independently associated with LPLN metastasis. CONCLUSIONS The size and signal intensity of LPLN before and after CRT are useful MRI findings to predict LPLN metastasis and are helpful to determine the indications for LPLD.
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Cirocco WC. Outcomes of rectal resection following neoadjuvant therapy in the elderly: Can rectal cancer patients be too old for a neoadjuvant approach? Am J Surg 2018; 215:436-439. [DOI: 10.1016/j.amjsurg.2017.10.049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Revised: 10/09/2017] [Accepted: 10/11/2017] [Indexed: 11/26/2022]
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Loftas P, Arbman G, Sun XF, Edler D, Syk E, Hallbook O. FXYD-3 expression in relation to local recurrence of rectal cancer. Radiat Oncol J 2016; 34:52-8. [PMID: 27104167 PMCID: PMC4831969 DOI: 10.3857/roj.2016.34.1.52] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 02/17/2016] [Accepted: 03/14/2016] [Indexed: 01/07/2023] Open
Abstract
Purpose In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. Materials and Methods FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81). Results Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without. Conclusion Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.
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Affiliation(s)
- Per Loftas
- Division of Surgery, Department of Clinical and Experimental Medicine, Linkoping University, Norrkoping, Sweden
| | - Gunnar Arbman
- Division of Surgery, Department of Clinical and Experimental Medicine, Linkoping University, Norrkoping, Sweden
| | - Xiao-Feng Sun
- Division of Oncology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden
| | - David Edler
- Department of Surgery, Karolinska Institute, Stockholm, Sweden
| | - Erik Syk
- Department of Surgery, Ersta Hospital, Stockholm, Sweden
| | - Olof Hallbook
- Division of Surgery, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden
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Garcia-Aguilar J, Glynne-Jones R, Schrag D. Multimodal Rectal Cancer Treatment: In Some Cases, Less May Be More. Am Soc Clin Oncol Educ Book 2016; 35:92-102. [PMID: 27249690 DOI: 10.1200/edbk_159221] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
A series of clinical trials in the last several decades has resulted in the development of multimodality treatment of locally advanced rectal cancer that includes neoadjuvant (preoperative) chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemoradiotherapy. Owing to this regimen, patients with locally advanced rectal cancer have better survival rates than patients with colon cancer, but at the cost of substantial morbidity and reduced quality of life. The challenge is to identify treatment approaches that maintain or even improve oncologic outcomes while preserving quality of life. We have identified different tumor characteristics that are associated with recurrence and probability of survival for locally advanced rectal cancer. This risk stratification, based on baseline clinical staging and tumor response to chemoradiotherapy, has led us to question whether all patients with locally advanced rectal cancer require every component of the multimodal regimen. In this article, we will review recent evidence that some patients with locally advanced rectal cancer can be spared one or more treatment modalities without compromising long-term oncologic outcomes and while preserving quality of life.
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Affiliation(s)
- Julio Garcia-Aguilar
- From the Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, London, United Kingdom; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
| | - Rob Glynne-Jones
- From the Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, London, United Kingdom; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
| | - Deborah Schrag
- From the Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, London, United Kingdom; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
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Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI. Eur Radiol 2015; 26:297-305. [PMID: 26017737 DOI: 10.1007/s00330-015-3837-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Revised: 04/21/2015] [Accepted: 05/08/2015] [Indexed: 01/03/2023]
Abstract
OBJECTIVES To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) METHODS: Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis. RESULTS In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59%, and 89.47%, respectively) were significantly higher than those of LVI (64.86%, and 61.76%), but sensitivity and negative predictive value were not significantly different between MVI (60.71%, and 76.09%) and LVI (75.00%, and 77.42%). CONCLUSIONS While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI. KEY POINTS • Mesorectal vascular invasion (MVI) may be a radiologic prognostic factor for rectal cancer. • Specificity of MVI was higher than lymphovascular invasion in predicting early metastasis. • Mesorectal vascular invasion may be a better predictor for early distant metastasis.
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Minicozzi P, Bouvier AM, Faivre J, Sant M. Management of rectal cancers in relation to treatment guidelines: a population-based study comparing Italian and French patients. Dig Liver Dis 2014; 46:645-51. [PMID: 24746280 DOI: 10.1016/j.dld.2014.03.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 02/15/2014] [Accepted: 03/16/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Few studies have investigated rectal cancer management at the population level. We compared how rectal cancers diagnosed in Italy (2003-2005) and France (2005) were managed, and evaluated the extent to which management adhered to European guidelines. METHODS Samples of 3938 Italian and 2287 French colorectal cancer patients were randomly extracted from 8 and 12 cancer registries respectively. Rectal cancer patients (860 Italian, 559 French) were analysed. Logistic regression models estimated odds ratios (ORs) of being treated with curative intent, receiving sphincter-saving surgery, and receiving preoperative radiotherapy. RESULTS Similar proportions of Italian and French patients were treated with curative intent (70% vs. 67%; OR=0.92 [0.73-1.16]); the respective proportions receiving sphincter-saving surgery were 21% and 33% (OR=1.15 [0.86-1.53]). In about 50% of those treated with curative intent, ≥ 12 lymph nodes were harvested in both countries. The proportion receiving postoperative radiotherapy was higher in Italy than in France (25% vs. 11%, p<0.01), but French patients were more likely to receive preoperative radiotherapy (52% vs. 21%; OR=4.06 [2.79-5.91]). CONCLUSION The proportions of patients receiving preoperative radiotherapy and the numbers of lymph nodes sampled were low in both countries. Centralising treatment and potentiating screening would be practical ways of improving outcomes and adhering to guidelines.
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Affiliation(s)
- Pamela Minicozzi
- Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Anne-Marie Bouvier
- Digestive Cancers Registry of Burgundy, University Hospital Dijon, Inserm U866, University of Burgundy, Dijon, France; FRANCIM (French Network of Cancer Registries), France
| | - Jean Faivre
- Digestive Cancers Registry of Burgundy, University Hospital Dijon, Inserm U866, University of Burgundy, Dijon, France; FRANCIM (French Network of Cancer Registries), France
| | - Milena Sant
- Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Hida JI, Okuno K, Tokoro T. Distal dissection in total mesorectal excision, and preoperative chemoradiotherapy and lateral lymph node dissection for rectal cancer. Surg Today 2013; 44:2227-42. [PMID: 24363114 DOI: 10.1007/s00595-013-0811-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 11/05/2013] [Indexed: 01/26/2023]
Abstract
The local recurrence rate after total mesorectal excision (TME) appears to be markedly lower than that after conventional operations. We reviewed all relevant articles identified from the MEDLINE databases and clarified the rationale for TME. It is clear that distal intramural spread is rare. Even when present, such spread is not likely to extend beyond 2 cm. Data with attention to mesorectal cancer deposits suggest that mesorectal clearance of at least 4-5 cm distal to the tumor should be sufficient. TME should be performed for most tumors of the mid- and lower rectum. This does not mean that the gut tube needs to be divided at the same level in every case. Dissection of the distal mesorectum off the gut tube can be performed, so the distal line of division of the bowel wall can be made at a minimum of 2 cm below the tumor if such a maneuver would ensure that the sphincters are preserved. In cases with cancer in the upper third of the rectum, the mesorectum and gut tube can safely be divided 5 cm below the tumor without jeopardizing the recurrence rates. Our findings indicate that TME is an essential treatment approach for rectal cancer, and lateral lymph node dissection and preoperative chemoradiotherapy are additional therapies that should be considered for advanced rectal cancer.
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Affiliation(s)
- Jin-ichi Hida
- Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan,
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Glynne-Jones R, Harrison M, Hughes R. Challenges in the neoadjuvant treatment of rectal cancer: balancing the risk of recurrence and quality of life. Cancer Radiother 2013; 17:675-85. [PMID: 24183502 DOI: 10.1016/j.canrad.2013.06.043] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 06/21/2013] [Indexed: 01/01/2023]
Abstract
The management of patients with rectal cancer has improved substantially-assisted by refinements in surgical technique, the increasing accuracy of preoperative imaging, more precise delivery of radiotherapy¸and more informative feedback from the histopathologist. Multidisciplinary teams have been the key to this success. Future challenges facing multidisciplinary teams include individually tailoring therapy - in particular in deciding who does and does not need radiotherapy, utilising new radiotherapy techniques such as intensity-modulated radiotherapy and image-guided radiotherapy and new systemic therapies, and electing patients for whom chemoradiotherapy might be potentially curative without surgical resection after complete clinical response. Hence, there is an increasing focus on developing predictive and prognostic molecular biomarkers. This paper explores the background to common variations in practice, and the current and future challenges in the neoadjuvant treatment of rectal cancer.
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Affiliation(s)
- R Glynne-Jones
- Radiotherapy Department, Mount-Vernon Cancer Centre, Mount-Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom.
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Sanz-Pamplona R, Berenguer A, Cordero D, Riccadonna S, Solé X, Crous-Bou M, Guinó E, Sanjuan X, Biondo S, Soriano A, Jurman G, Capella G, Furlanello C, Moreno V. Clinical value of prognosis gene expression signatures in colorectal cancer: a systematic review. PLoS One 2012; 7:e48877. [PMID: 23145004 PMCID: PMC3492249 DOI: 10.1371/journal.pone.0048877] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2012] [Accepted: 10/02/2012] [Indexed: 12/01/2022] Open
Abstract
Introduction The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC) at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets. Methods A literature review identified 31 gene expression signatures that used gene expression data to predict prognosis in CRC tissue. The search was based on the PubMed database and was restricted to papers published from January 2004 to December 2011. Eleven CRC gene expression datasets with outcome information were identified and downloaded from public repositories. Random Forest classifier was used to build predictors from the gene lists. Matthews correlation coefficient was chosen as a measure of classification accuracy and its associated p-value was used to assess association with prognosis. For clinical usefulness evaluation, positive and negative post-tests probabilities were computed in stage II and III samples. Results Five gene signatures showed significant association with prognosis and provided reasonable prediction accuracy in their own training datasets. Nevertheless, all signatures showed low reproducibility in independent data. Stratified analyses by stage or microsatellite instability status showed significant association but limited discrimination ability, especially in stage II tumors. From a clinical perspective, the most predictive signatures showed a minor but significant improvement over the classical staging system. Conclusions The published signatures show low prediction accuracy but moderate clinical usefulness. Although gene expression data may inform prognosis, better strategies for signature validation are needed to encourage their widespread use in the clinic.
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Affiliation(s)
- Rebeca Sanz-Pamplona
- Unit of Biomarkers and Susceptibility (UBS), Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain
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Rondelli F, Trastulli S, Cirocchi R, Avenia N, Mariani E, Sciannameo F, Noya G. Rectal washout and local recurrence in rectal resection for cancer: a meta-analysis. Colorectal Dis 2012; 14:1313-21. [PMID: 22150936 DOI: 10.1111/j.1463-1318.2011.02903.x] [Citation(s) in RCA: 31] [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
AIM The effectiveness of rectal washout was compared with no washout for the prevention of local recurrence after anterior rectal resection for rectal cancer. METHOD The following electronic databases were searched: PubMed, OVID Medline, Cochrane Database of Systematic Reviews, EBM Reviews, CINAHL and EMBASE. RESULTS Five nonrandomized studies including a total of 5012 patients were identified. Meta-analysis suggested that rectal washout significantly reduced the local recurrence rate (P < 0.0001; OR 0.57; 95% CI 0.43-0.74). It was also significantly lower after washout in patients having radical resection only (P = 0.0004; OR 0.54; 95% CI 0.39-0.76), patients treated by a curative resection (P < 0.0001; OR 0.55; 95% CI 0.42-0.72) and those undergoing preoperative radiotherapy (P = 0.04; OR 0.62; 95% CI 0.39-0.98). CONCLUSION Taking into account the limitations of the design of the included studies the meta-analysis showed that rectal washout is associated with reduced local recurrence and therefore should be routine during anterior resection for rectal cancer.
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Affiliation(s)
- F Rondelli
- Department of General and Oncologic Surgery, University of Perugia, Perugia, Italy
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Archampong D, Borowski D, Wille-Jørgensen P, Iversen LH. Workload and surgeon's specialty for outcome after colorectal cancer surgery. Cochrane Database Syst Rev 2012; 2012:CD005391. [PMID: 22419309 PMCID: PMC12076000 DOI: 10.1002/14651858.cd005391.pub3] [Citation(s) in RCA: 121] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND A large body of research has focused on investigating the effects of healthcare provider volume and specialization on patient outcomes including outcomes of colorectal cancer surgery. However there is conflicting evidence about the role of such healthcare provider characteristics in the management of colorectal cancer. OBJECTIVES To examine the available literature for the effects of hospital volume, surgeon caseload and specialization on the outcomes of colorectal, colon and rectal cancer surgery. SEARCH METHODS We searched Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS using free text search words (as well as MESH-terms). We also searched Medline (January 1990-September 2011), Embase (January 1990-September 2011) and registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA Non-randomised and observational studies that compared outcomes for colorectal cancer, colon cancer and rectal cancer surgery (overall 5-year survival, five year disease specific survival, operative mortality, 5-year local recurrence rate, anastomotic leak rate, permanent stoma rate and abdominoperineal excision of the rectum rate) between high volume/specialist hospitals and surgeons and low volume/specialist hospitals and surgeons. DATA COLLECTION AND ANALYSIS Two review authors independently abstracted data and assessed risk of bias in included studies. Results were pooled using the random effects model in unadjusted and case-mix adjusted meta-analyses. MAIN RESULTS Overall five year survival was significantly improved for patients with colorectal cancer treated in high-volume hospitals (HR=0.90, 95% CI 0.85 to 0.96), by high-volume surgeons (HR=0.88, 95% CI 0.83 to 0.93) and colorectal specialists (HR=0.81, 95% CI 0.71 to 0.94). Operative mortality was significantly better for high-volume surgeons (OR=0.77, 95% CI 0.66 to 0.91) and specialists (OR=0.74, 95% CI 0.60 to 0.91), but there was no significant association with higher hospital caseload (OR=0.93, 95% CI 0.84 to 1.04) when only case-mix adjusted studies were included. There were differences in the effects of caseload depending on the level of case-mix adjustment and also whether the studies originated in the US or in other countries. For rectal cancer, there was a significant association between high-volume hospitals and improved 5-year survival (HR=0.85, 95% CI 0.77 to 0.93), but not with operative mortality (OR=0.97, 95% CI 0.70 to 1.33); surgeon caseload had no significant association with either 5-year survival (HR=0.99, 95% CI 0.86 to 1.14) or operative mortality (OR=0.86, 95% CI 0.62 to 1.19) when case-mix adjusted studies were reviewed. Higher hospital volume was associated with significantly lower rates of permanent stomas (OR=0.64, 95% CI 0.45 to 0.90) and APER (OR=0.55, 95% CI 0.42 to 0.72). High-volume surgeons and specialists also achieved lower rates of permanent stoma formation (0.75, 95% CI 0.64 to 0.88) and (0.70, 95% CI 0.53 to 0.94, respectively). AUTHORS' CONCLUSIONS The results confirm clearly the presence of a volume-outcome relationship in colorectal cancer surgery, based on hospital and surgeon caseload, and specialisation. The volume-outcome relationship appears somewhat stronger for the individual surgeon than for the hospital; particularly for overall 5-year survival and operative mortality, there were differences between US and non-US data, suggesting provider variability at hospital level between different countries, making it imperative that every country or healthcare system must establish audit systems to guide changes in the service provision based on local data, and facilitate centralisation of services as required. Overall quality of the evidence was low as all included studies were observational by design. In addition there were discrepancies in the definitions of caseload and colorectal specialist. However ethical challenges associated with the conception of randomised controlled trials addressing the volume outcome relationship makes this the best available evidence.
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Affiliation(s)
- David Archampong
- Department of Surgery, University Hospital Wales, Cardiff, Wales, UK.
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Wang Z, Loh KY, Tan KY, Woo ECH. The role of lateral lymph node dissection in the management of lower rectal cancer. Langenbecks Arch Surg 2012; 397:353-361. [PMID: 22105772 DOI: 10.1007/s00423-011-0864-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2011] [Accepted: 10/10/2011] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Lateral lymph node involvement is a problem encountered in patients with low rectal cancers. This has been documented in both anatomical and pathological studies. Currently, the vast majority of centers have concentrated on the use of chemoradiation to obtain better local control and manage these nodes indirectly. In Japan, extended nodal dissection for the control of pelvic nodal disease has seen further advancement. This paper discusses the key issues involved in the management of pelvic lateral nodes in low rectal cancers. METHODS A review of available literature and critical appraisal of the entity of lateral nodes in low rectal cancers, the treatment options, and oncological and functional results were performed. RESULTS There are good data showing that the entity of pelvic lateral nodes in low rectal cancers should not be ignored. Recent data have emerged showing that radiotherapy is associated with significant long-term functional side effects. Refinement of the technique, lateral node dissection, has led to good local control as well as good functional outcomes. CONCLUSION In this context, there needs to be a reevaluation of the role of chemoradiation as the sole treatment for lateral nodal disease in centers outside of Japan. Individualization of the treatment of rectal cancer may require all centers to be able to offer both modalities.
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Affiliation(s)
- Ziting Wang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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de la Fuente SG, Ludwig KA, Tyler DS, Mantyh CR. Ex Vivo Evaluation of Preoperatively Treated Rectal Cancer Specimens of Patients Undergoing Radical Resection. Ann Surg Oncol 2012; 19:1954-8. [DOI: 10.1245/s10434-012-2259-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Indexed: 11/18/2022]
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Chen ZH, Song XM, Chen SC, Li MZ, Li XX, Zhan WH, He YL. Risk factors for adverse outcome in low rectal cancer. World J Gastroenterol 2012; 18:64-9. [PMID: 22228972 PMCID: PMC3251807 DOI: 10.3748/wjg.v18.i1.64] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2011] [Revised: 07/07/2011] [Accepted: 07/14/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To demonstrate the oncologic outcomes of low rectal cancer and to clarify the risk factors for survival, focusing particularly on the type of surgery performed.
METHODS: Data from patients with low rectal carcinomas who underwent surgery, either sphincter-preserving surgery (SPS) or abdominoperineal resection (APR), at The First Affiliated Hospital of Sun Yat-sen University in China from August 1994 to December 2005 were retrospectively analyzed.
RESULTS: Of 331 patients with low rectal cancer, 159 (48.0%) were treated with SPS. A higher incidence of positive resection margins and a higher 5-year cumulative local recurrence rate (14.7% vs 6.8%, P = 0.041) were observed in patients after APR compared to SPS. The five-year overall survival (OS) was 54.6% after APR and 66.8% after SPS (P = 0.018), and the 5-year disease-free survival (DFS) was 52.9% after APR and 65.5% after SPS (P = 0.013). In multivariate analysis, poor OS and DFS were significantly related to positive resection margins, pT3-4, and pTNM III-IV but not to the type of surgery.
CONCLUSION: Despite a higher rate of positive resection margins after APR, the type of surgery was not identified as an independent risk factor for survival.
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Extended abdominoperineal excision vs. standard abdominoperineal excision in rectal cancer--a systematic overview. Int J Colorectal Dis 2011; 26:1227-40. [PMID: 21603901 DOI: 10.1007/s00384-011-1235-3] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/03/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND After introduction of total mesorectal excision (TME) as the gold standard for rectal cancer surgery, oncologic results appeared to be inferior for abdominoperineal excision (APE) as compared to anterior resection. This has been attributed to the technique of standard APE creating a waist at the level of the tumor-bearing segment. This systematic review investigates outcome of both standard and extended techniques of APE regarding inadvertent bowel perforation, circumferential margin (CRM) involvement, and local recurrence. METHODS A literature search was performed to identify all articles reporting on APE after the introduction of TME using Medline, Ovid, and Embase. Extended APE was defined as operations that resected the levator ani muscle close to its origin. All other techniques were taken to be standard. Studies so identified were evaluated using a validated instrument for assessing nonrandomized studies. Rates for perforation, CRM involvement, and local recurrence were compared using chi-square statistics. RESULTS In the extended group, 1,097 patients, and in the standard group, 4,147 patients could be pooled for statistical analysis. The rate of inadvertent bowel perforation and the rate of CRM involvement for extended vs. standard APE was 4.1% vs. 10.4% (relative risk reduction 60.6%, p = 0.004) and 9.6% vs. 15.4% (relative risk reduction 37.7%, p = 0.022), respectively. The local recurrence rate was 6.6% vs. 11.9% (relative risk reduction 44.5%, p < 0.001) for the two groups. CONCLUSION This systematic review suggests that extended techniques of APE result in superior oncologic outcome as compared to standard techniques.
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Stelzner S, Hellmich G, Schubert C, Puffer E, Haroske G, Witzigmann H. Short-term outcome of extra-levator abdominoperineal excision for rectal cancer. Int J Colorectal Dis 2011; 26:919-25. [PMID: 21350936 DOI: 10.1007/s00384-011-1157-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND Extra-levator abdominoperineal excision (ELAPE) has been introduced to avoid oncologic problems encountered with conventional abdominoperineal excision (APE) such as high rates of inadvertent bowel perforation and of positive circumferential resection margin. We compare our short-term results of this new approach with a historic patient cohort. PATIENTS AND METHODS From 1997 until 2010, we performed 46 consecutive conventional APE and 28 ELAPE after neoadjuvant therapy with a macroscopically complete resection in the true pelvis. Patient data was prospectively collected in our colorectal tumor database. Patient and tumor characteristics were compared as were the rates of inadvertent bowel perforation, of circumferential margin involvement, and of wound abscesses. RESULTS The rates of inadvertent bowel perforation, of circumferential margin involvement, and of wound abscesses were 15.2% vs. 0 (p = 0.04), 4.9% vs. 0 (p = 0.511), and 17.4% vs. 10.7% (p = 0.518), respectively, in the conventional APE vs. ELAPE group. CONCLUSION With a significant reduction of the bowel perforation rate and a reduction of circumferential margin involvement and wound abscess formation, ELAPE improves important surrogate parameters for local recurrence rate and survival.
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Affiliation(s)
- Sigmar Stelzner
- Department of General and Visceral Surgery, Dresden-Friedrichstadt General Hospital, Dresden, Germany.
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