Down-staging following neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: Does timing of surgery really matter? (original) (raw)
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Journal of cancer research and clinical oncology, 2014
The optimal waiting period between neoadjuvant treatment completion and surgery in locally advanced rectal cancer (LARC) is controversial. The specific purpose of this study was to evaluate the effect of prolonging this interval on the pathologic response, postoperative morbidity, and long-term oncologic outcomes. Retrospective data analysis is reported from LARC patients who had been treated with chemoradiation followed by surgery and intra-operative radiotherapy, between February 1995 and December 2012. In total, two groups were studied, according to the time elapsed between neoadjuvant treatment and surgery: conventional interval (CI; <6 weeks) and delayed interval (DI; ≥6 weeks). Clinicopathological data related to tumor response, postoperative morbidity, and oncologic outcomes were compared. This study included 335 consecutive LARC patients. There was a higher proportion of patients with clinical staging nodal involvement (cN+) in the DI group (76.6 vs. 64.1 %; p = 0.01). Th...
Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
Journal of The American College of Surgeons, 2016
BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has demonstrated proven benefit in tumor regression and improved long-term local control for patients with locally advanced rectal cancer. However, precise analysis of the optimal waiting time that maximizes oncologic benefits of nCRT has not been established. STUDY DESIGN: The 2006e2012 National Cancer Data Base was queried for patients with stage II and III rectal adenocarcinoma who underwent nCRT followed by surgical resection. Time to surgery was defined as the difference between last date of radiotherapy and date of surgery. Primary study endpoints included resection margin positivity and pathologic downstaging. Multivariable regression modeling with restricted cubic splines was used to evaluate the adjusted association between time to surgery and our study endpoints, and to establish an optimal time threshold for surgery. RESULTS: A total of 11,760 patients were included. Median time to surgery was 53 days (interquartile range [IQR] 43 to 63 days). After adjusting for patient demographic, clinical, tumor, and treatment characteristics, our model determined an inflection point at 56 days after end of radiotherapy associated with the highest likelihood of complete resection and pathologic downstaging. With adjustment, the risk of margin positivity was increased in those who underwent surgery after 56 days from end of radiotherapy (odds ratio [OR] 1.40, 95% CI 1.21 to 1.61, p < 0.001). The likelihood of downstaging was increasing up to 56 days after radiotherapy (56 days vs <56 days, OR 1.2, 95% CI 1.02 to 1.23, p ¼ 0.01). CONCLUSIONS: This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the critical threshold for optimal tumor response.
Optimal timing of surgery after neoadjuvant chemoradiation therapy in locally advanced rectal cancer
Journal of the Korean Surgical Society, 2013
The optimal time between neoadjuvant chemoradiotherapy (CRT) and surgery for rectal cancer has been debated. This study evaluated the influence of this interval on oncological outcomes. We compared postoperative complications, pathological downstaging, disease recurrence, and survival in patients with locally advanced rectal cancer who underwent surgical resection <8 weeks (group A, n = 105) to those who had surgery ≥8 weeks (group B, n = 48) after neoadjuvant CRT. Of 153 patients, 117 (76.5%) were male and 36 (23.5%) were female. Mean age was 57.8 years (range, 28 to 79 years). There was no difference in the rate of sphincter preserving surgery between the two groups (group A, 82.7% vs. group B, 77.6%; P = 0.509). The longer interval group had decreased postoperative complications, although statistical significance was not reached (group A, 28.8% vs. group B, 14.3%; P = 0.068). A total of 111 (group A, 75 [71.4%] and group B, 36 [75%]) patients were downstaged and 26 (group A, 1...
BMC Cancer, 2013
Background: Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery.
Clinical and Translational Radiation Oncology
To report on organ preservation following chemoradiotherapy (CRT) in a prospective cohort of locally advanced rectal cancer patients. Methods and materials: Fifty-two patients received CRT. MRI and 18 F-FDG-PET/CT were performed prior to CRT. Response assessment was done 6 and 12 weeks after CRT using digital rectal examination, MRI, 18 F-FDG-PET/CT and endoscopy. For clinical complete response or minimal residual disease, a watch-and-wait (W&W) protocol was started. Regrowth-free survival (ReFS), Total Mesorectal Excision-free disease-free survival, distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using Kaplan-Meier method. Functional outcome was compared with the Wilcoxon signed-rank test using EORTC QLQ-C30, MSKCC BFI, LARS and IIEF-5/FSFI-5 questionnaires. A previously developed prediction model performance was tested using receiver operating characteristic analysis. Results: 29/52 patients entered a W&W protocol. There was no difference in two-year DMFS (81.1 % vs 78.8 %, p = 0.82), two-year OS (96.4 % vs 100 %, p = 0.38) and two-year DFS (77.5 % vs 78.8 %, p = 0.87) between W&W patients and those who underwent surgery at 12 weeks after CRT. Two-year DMFS differed between W&W with local regrowth, W&W with sustained response and patients who had surgery (66.7 % vs 88.0 % vs 78.8 %; p = 0.04). At 6 and 12 months, W&W patients reported good QoL and bowel function. The model validation reached an AUC of 0.627. Conclusion: Good functional outcome in patients with rectal cancer allocated to surveillance after CRT needs to be balanced against potentially worse DMFS in a subset of patients without sustained clinical complete response. Reliable prediction of patients eligible for surveillance programs needs further investigation.
Cancers, 2018
There is ongoing debate regarding the significance of complete or near-complete response after neoadjuvant chemoradiotherapy (CRT) for rectal cancer. This study assessed the prognostic value of the Dworak tumor regression grade (TRG) following neoadjuvant CRT and surgery primarily in patients with pathological stage (ypStage) II and III rectal cancer. The records of 331 patients who underwent neoadjuvant CRT followed by total mesorectal excision between 2004 and 2015 were retrospectively reviewed. Patients were categorized as having a good response (GR, TRG 3/4, = 122) or a poor response (PR, TRG 1/2, = 209). At a median follow-up of 65 months, five-year disease-free survival (DFS) was higher in the GR group than in the PR group (91.3% vs. 66.6%, < 0.001). Patients with a GR and ypStage II disease had a five-year DFS that was indistinguishable from that of patients with ypStage 0⁻I disease (92.3% vs. 90.7%, = 0.885). Likewise, patients with a GR and ypStage III disease had a five...
South Asian Journal of Cancer
Background Polish and Australian randomized studies compared short-course radiotherapy (RT) with immediate surgery and long-course chemoradiotherapy (CRT) with delayed surgery. In these studies, similar long-term survival and local control have been reported for both these approaches, but pathological complete response (pCR) is not better with short-course RT. Moreover, studies have shown better tumor downstaging with delayed surgery. In this context, the use of short-course RT with delayed surgery may have some advantages and needs to be tested in clinical trials. Patients and Methods This was a two-arm, prospective, observational study, in which preoperative short-course RT followed by two cycles of chemotherapy was compared with the conventional neoadjuvant CRT in locally advanced rectal cancer. The primary end points were the rate of complete response and toxicity profile. The secondary end points were the rate of R0 resection, overall survival, and progression-free survival. Th...
Background: To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. Methods: A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7–12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. Results: Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adeno-carcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001), respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while 3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p < 0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001) were significantly