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Neoadjuvant radiotherapy improves overall survival for T3/4N+M0 rectal cancer patients: a population-based study of 20300 patients.

ABSTRACT: BACKGROUND:Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N?+?M0) on the OS of rectal cancer patients. METHODS:Date from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2016 were used. Kaplan-Meier analyses were used to compare patient prognoses across different treatment modalities. Cox hazard regression analysis were used to identify independent predictors of OS. RESULTS:For stage T3/4N0M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p?>?0.05; mean survival, 115.89?months (M), 111.97?M, and 117.22?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p??0.05; mean survival, 121.50?M, 124.25?M, and 121.20?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p??60?years), black race, unmarried status, high tumour grade, and tumour size >?5?cm were all associated with a poor prognosis (all p?

SUBMITTER: Zhao F

PROVIDER: S-EPMC7045410 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Neoadjuvant radiotherapy improves overall survival for T3/4N+M0 rectal cancer patients: a population-based study of 20300 patients.

Zhao Feng F Wang Jili J Yu Hao H Cheng Xiaofei X Li Xinke X Zhu Xuan X Xu Xiangming X Lin Jianjiang J Chen Xin X Yan Senxiang S

Radiation oncology (London, England) 20200227 1

<h4>Background</h4>Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N + M0) on the OS of rectal cancer patients.<h4>Methods</h4>Date from the Surveillance, Epidemiology, and ...[more]

PMID: 32103755

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Project description:Importance:Although American guidelines recommend use of adjuvant chemotherapy in patients with locally advanced rectal cancer, individuals who achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy are less likely to receive adjuvant treatment than incomplete responders. The association and resection of adjuvant chemotherapy with survival in patients with pCR is unclear. Objective:To determine whether patients with locally advanced rectal cancer who achieve pCR after neoadjuvant chemoradiation therapy and resection benefit from the administration of adjuvant chemotherapy. Design, Setting, and Participants:This retrospective propensity score-matched cohort study identified patients with locally advanced rectal cancer from the National Cancer Database from 2006 through 2012. We selected patients with nonmetastatic invasive rectal cancer who achieved pCR after neoadjuvant chemoradiation therapy and resection. Exposures:We matched patients who received adjuvant chemotherapy to patients who did not receive adjuvant treatment in a 1:1 ratio. We separately matched subgroups of patients with node-positive disease before treatment and node-negative disease before treatment to investigate for effect modification by pretreatment nodal status. Main Outcome and Measures:We compared overall survival between groups using Kaplan-Meier survival methods and Cox proportional hazards models. Results:We identified 2455 patients (mean age, 59.5 years; 59.8% men) with rectal cancer with pCR after neoadjuvant chemoradiation therapy and resection. We matched 667 patients with pCR who received adjuvant chemotherapy and at least 8 weeks of follow-up after surgery to patients with pCR who did not receive adjuvant treatment. Over a median follow-up of 3.1 years (interquartile range, 1.94-4.40 years), patients treated with adjuvant chemotherapy demonstrated better overall survival than those who did not receive adjuvant treatment (hazard ratio, 0.44; 95% CI, 0.28-0.70). When stratified by pretreatment nodal status, only those patients with pretreatment node-positive disease exhibited improved overall survival with administration of adjuvant chemotherapy (hazard ratio, 0.24; 95% CI, 0.10-0.58). Conclusions and Relevance:The administration of adjuvant chemotherapy in patients with rectal cancer with pCR is associated with improved overall survival, particularly in patients with pretreatment node-positive disease. Although this study suggests a beneficial effect of adjuvant treatment on survival in patients with pCR, these results are limited by the presence of potential unmeasured confounding in this nonrandomized study.

Project description:Importance:Adjuvant chemotherapy (AC) in patients with rectal cancer with pathologic complete response following neoadjuvant chemoradiotherapy (nCRT) and resection is recommended by treatment guidelines. However, its role in this setting is equivocal because data supporting benefits are lacking. Objective:To compare the overall survival (OS) between AC and postoperative observation (OB) in patients with rectal cancer with pathologic complete response following nCRT and resection. Design, Setting, and Participants:We identified a cohort of patients with rectal cancer and a complete pathological response (ypT0N0) after nCRT in the National Cancer Database between 2006 and 2012. Patients who received AC were compared with OB patients by propensity score matching. Overall survival was compared using the stratified log-rank test and stratified Cox regression model. The outcomes after AC vs OB were also evaluated in patient subgroups. The data analysis was completed in June 2017. Exposures:Adjuvant chemotherapy and OB. Main Outcomes and Measures:Overall survival. Results:We identified 2764 patients (mean [SD] age, 60.0 [12.3] years; 40% female) with clinical stage II or III resected adenocarcinoma of the rectum who had received nCRT and were complete responders (ypT0N0M0). Of this cohort, 741 patients in the AC group were matched by propensity score to 741 patients who underwent OB. The AC cohort had better OS compared with the OB cohort (hazard ratio, 0.50; 95% CI, 0.32-0.79). The 1-, 3-, and 5-year OS rates were 99.7%, 97.1%, and 94.7% for the AC group and 99.2%, 93.6%, and 88.4% for the OB group (P = .005). In subgroup analysis, patients with clinical stage T3/T4 and node-positive disease benefited most from AC (hazard ratio, 0.47; 95% CI, 0.25-0.91). Conclusions and Relevance:Adjuvant chemotherapy was associated with improved OS in patients with pathologic complete response after nCRT for resected locally advanced rectal cancer. This study supports the use of AC in this setting where there is currently paucity of data.

Project description:IntroductionIn locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients.MethodsA retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression.ResultsFrom a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery.ConclusionsThere was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

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Neoadjuvant radiotherapy improves overall survival for T3/4N+M0 rectal cancer patients: a population-based study of 20300 patients.

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Neoadjuvant radiotherapy improves overall survival for T3/4N+M0 rectal cancer patients: a population-based study of 20300 patients.

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