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. 2019 Apr 1;5(4):e185896.
doi: 10.1001/jamaoncol.2018.5896. Epub 2019 Apr 11.

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

J Joshua Smith  1 , Paul Strombom  1 , Oliver S Chow  1 , Campbell S Roxburgh  1   2 , Patricio Lynn  1 , Anne Eaton  3 , Maria Widmar  1 , Karuna Ganesh  4 , Rona Yaeger  4 , Andrea Cercek  4 , Martin R Weiser  1 , Garrett M Nash  1 , Jose G Guillem  1 , Larissa K F Temple  1 , Sree B Chalasani  4 , James L Fuqua  5 , Iva Petkovska  5 , Abraham J Wu  6 , Marsha Reyngold  6 , Efsevia Vakiani  7 , Jinru Shia  7 , Neil H Segal  4 , James D Smith  1 , Christopher Crane  6 , Marc J Gollub  5 , Mithat Gonen  3 , Leonard B Saltz  4 , Julio Garcia-Aguilar  1 , Philip B Paty  1
Affiliations

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

J Joshua Smith et al. JAMA Oncol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr J. J. Smith 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.

Figures

Figure 1.
Figure 1.. Selection of Patients Included in the Watch-and-Wait and Pathologic Complete Response (pCR) Groups
Patients were included in the watch-and-wait arm if they had a clinical complete response (cCR) prior to January 31, 2015 (n = 113). Patients were included in the pCR arm if they underwent total mesorectal excision (TME) and had a pCR (n = 136).
Figure 2.
Figure 2.. Local Regrowth and Rectal Preservation in the Watch-and-Wait Cohort
At 5 years, the rate of local regrowth was 21%. After a median follow-up of 33 months from the end of neoadjuvant therapy, 22 of the 113 patients (19.5%) included in the watch-and-wait group developed a local regrowth, which corresponds to a 5-year actuarial rate of 21.4% (95% CI, 12%-30%) and thus an organ preservation rate of 79% (95% CI, 70%-88%).
Figure 3.
Figure 3.. Overall Survival, Disease-Free Survival, and Disease-Specific Survival at 5 Years in the Watch-and-Wait Cohort
For the watch-and-wait group, (A) overall survival is 73% (95% CI, 60%-89%), (B) disease-free survival is 75% (95% CI, 62%-90%), and (C) disease-specific survival is 90% (95% CI, 81%-99%). In the overall survival analysis, 70% of the watch-and-wait group died of other causes. Survival was measured from the end of neoadjuvant treatment. The disease-free survival events included locoregional recurrence, distant recurrence, and death from any cause, but specifically excluded local regrowth.
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