A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis
TL;DR: Most patients treated by watch-and-wait avoid radical surgery and of those who have regrowth almost all have salvage therapy, and more prospective studies are needed to confirm long-term safety.
About: This article is published in The Lancet Gastroenterology & Hepatology.The article was published on 2017-07-01. It has received 356 citations till now. The article focuses on the topics: Neoadjuvant therapy & Radical surgery.
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TL;DR: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data.
593 citations
TL;DR: Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers and policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Abstract: Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. Design Systematic review and meta-analysis. Data sources Published studies in Medline from 1 January 2000 to 10 April 2020. Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
546 citations
TL;DR: 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 reg growth vs those without local regrowth.
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 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.
315 citations
TL;DR: The addition of induction or consolidation chemotherapy to standard neoadjuvant chemoradiotherapy results in a higher pCR rate, and large confirmatory trials should be carried out before a strong recommendation is made in favor of TNT.
Abstract: Background The addition of induction chemotherapy to concomitant neoadjuvant chemoradiation in locally advanced rectal cancer could increase pathological downstaging and act on occult micrometastatic disease, leading ultimately to a better outcome. A systematic review was carried out of the existing literature on the treatment outcomes of total neoadjuvant therapy (TNT) on locally advanced rectal cancer. TNT was defined as chemotherapy using cycles of induction and/or consolidation in conjunction with standard chemoradiotherapy prior to surgery. Methods A systematic search of PubMed, Embase, and the Cochrane Library was performed according to the PRISMA statement up until January 2019. The primary endpoints were complete pathologic response (pCR), disease-free survival, and overall survival rates. Results A total of 28 studies (3 retrospective and 25 prospective for a total of 3579 patients) were included in the final analysis (n = 2688 treated with TNT and n = 891 with neoadjuvant chemoradiotherapy therapy). The pooled pCR rate was 22.4% (95% CI 19.4%-25.7%) in all patients treated with TNT (n = 27 studies with data available). In n = 10 comparative studies with data available, TNT was found to increase the odds of pCR by 39% (1.40, 95% CI 1.08-1.81, P = 0.01). Conclusions The addition of induction or consolidation chemotherapy to standard neoadjuvant chemoradiotherapy results in a higher pCR rate. Given that the comparative analysis was derived from few randomized publications, large confirmatory trials should be carried out before a strong recommendation is made in favor of TNT.
215 citations
Cites result from "A watch-and-wait approach for local..."
...In a pooled analysis of 22 studies adopting a wait-and-see strategy, salvage therapy was possible in 95% of patients with tumor regrowth (15% of the total), and no difference in the OS rate (despite a poorer DFS rate compared to those who received surgery after a pCR) was observed.(37) Despite being generally safe, a recent case series showed that the high rate of rectal preservation associated with the wait-and-see approach may come at the cost of reduced OS rates and an increased risk of distant metastases in those who experience local recurrence....
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TL;DR: In rectal cancer patients with a cCR following neoadjuvant chemoradiotherapy, a Watch and Wait policy appears feasible and safe, and robust surveillance with early detection of regrowths allows a high rate of successful salvage surgery, without an increase in the risk of systemic disease, or adverse survival outcomes.
Abstract: Objective:The aim of this study was to evaluate the oncological and survival outcomes of a Watch and Wait policy in rectal cancer after a clinical complete response (cCR) following neoadjuvant chemoradiotherapy.Background:The detection of a cCR after neoadjuvant treatment may facilitate a nonoperati
171 citations
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TL;DR: The Newcastle-Ottawa Scale (NOS) as discussed by the authors was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results.
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TL;DR: The metafor package provides functions for conducting meta-analyses in R and includes functions for fitting the meta-analytic fixed- and random-effects models and allows for the inclusion of moderators variables (study-level covariates) in these models.
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TL;DR: In this paper, a rank-based data augmentation technique is proposed for estimating the number of missing studies that might exist in a meta-analysis and the effect that these studies might have had on its outcome.
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