Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients with a Complete Response after Neoadjuvant Therapy

J. Joshua Smith, Paul Strombom, Oliver S. Chow, Campbell S. Roxburgh, Patricio Lynn, Anne Eaton, Maria Widmar, Karuna Ganesh, Rona Yaeger, Andrea Cercek, Martin R. Weiser, Garrett M. Nash, Jose G. Guillem, Larissa K.F. Temple, Sree B. Chalasani, James L. Fuqua, Iva Petkovska, Abraham J. Wu, Marsha Reyngold, Efsevia VakianiJinru Shia, Neil H. Segal, James D. Smith, Christopher Crane, Marc J. Gollub, Mithat Gonen, Leonard B. Saltz, Julio Garcia-Aguilar, Philip B. Paty

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328 Scopus citations


Importance: The watch-and-wait (WW) strategy aims to spare patients with rectal cancer unnecessary resection. Objective: To analyze the outcomes of WW among patients with rectal cancer who had a clinical complete response to neoadjuvant therapy. Design, Setting, and Participants: This retrospective case series analysis conducted at a comprehensive cancer center in New York included patients who received a diagnosis of rectal adenocarcinoma between January 1, 2006, and January 31, 2015. The median follow-up was 43 months. Data analyses were conducted from June 1, 2016, to October 1, 2018. Exposures: Patients had a clinical complete response after completing neoadjuvant therapy and agreed to a WW strategy of active surveillance and possible salvage surgery (n = 113), or patients underwent total mesorectal excision and were found to have a pathologic complete response (pCR) at resection (n = 136). Main Outcomes and Measures: Kaplan-Meier estimates were used for analyses of local regrowth and 5-year rates of overall survival, disease-free survival, and disease-specific survival. Results: Compared with the 136 patients in the pCR group, the 113 patients in the WW group were older (median [range], 67.2 [32.1-90.9] vs 57.3 [25.0-87.9] years, P <.001) with cancers closer to the anal verge (median [range] height from anal verge, 5.5 [0.0-15.0] vs 7.0 [0.0-13.0] cm). All 22 local regrowths in the WW group were detected on routine surveillance and treated by salvage surgery (20 total mesorectal excisions plus 2 transanal excisions). Pelvic control after salvage surgery was maintained in 20 of 22 patients (91%). No pelvic recurrences occurred in the pCR group. Rectal preservation was achieved in 93 of 113 patients (82%) in the WW group (91 patients with no local regrowths plus 2 patients with local regrowths salvaged with transanal excision). At 5 years, overall survival was 73% (95% CI, 60%-89%) in the WW group and 94% (95% CI, 90%-99%) in the pCR group; disease-free survival was 75% (95% CI, 62%-90%) in the WW group and 92% (95% CI, 87%-98%) in the pCR group; and disease-specific survival was 90% (95% CI, 81%-99%) in the WW group and 98% (95% CI, 95%-100%) in the pCR group. A higher rate of distant metastasis was observed among patients in the WW group who had local regrowth vs those who did not have local regrowth (36% vs 1%, P <.001). Conclusions and Relevance: A WW strategy for select rectal cancer patients who had a clinical complete response after neoadjuvant therapy resulted in excellent rectal preservation and pelvic tumor control; however, in the WW group, worse survival was noted along with a higher incidence of distant progression in patients with local regrowth vs those without local regrowth.

Original languageEnglish (US)
JournalJAMA Oncology
Issue number4
StatePublished - Apr 2019

Bibliographical note

Funding Information:
reported receiving travel support from Intuitive Surgical and being an advisor for Endogenesis Inc. Dr Segal reported receiving research funding from Roche/Genentech, Pfizer, Merck & Co, Bristol-Myers Squibb, MedImmune/AstraZeneca, and Incyte and for being an advisor for Roche/ Genentech, Merck & Co, Bristol-Myers Squibb, MedImmune/AstraZeneca, Boehringer Ingelheim, Pfizer, Pieris Pharmaceuticals, PsiOxus Therapeutics, Synlogic, Aduro Biotech, Kyn Therapeutics, PureTech Ventures, Horizon Pharma, EMD Serono, Gritstone Oncology, Chugai Pharmaceutical Co Ltd, TRM Oncology, IFM Therapeutics, and Medscape. Dr Garcia-Aguilar reported receiving honoraria from Medtronic, Johnson & Johnson, and Intuitive Surgical. No other disclosures were reported.

Funding Information:
Funding/Support: This work was supported by the following: grants P30-CA008748 and 5R01-CA182551-04 from the National Cancer Institute; a Career Development Award and a Limited Project Grant from the American Society of Colon and Rectal Surgeons; a Joel J. Roslyn Faculty Research Award from the Association of Academic Surgery; a Junior Faculty Award from the Memorial Sloan Kettering Cancer Center Department of Surgery; the Wasserman Colon and Rectal Cancer Fund; the Berezuk Colorectal Cancer Fund; and in part by the Colorectal Cancer Dream Team Translational Research Grant SU2C: AACR-DR22-17 from Stand Up to Cancer (an Entertainment Industry Foundation program, with research grants administered by the American Association of Cancer Research).

Publisher Copyright:
© 2019 American Medical Association. All rights reserved.


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