Peri-treatment change of anorectal function in patients with rectal cancer after preoperative chemoradiotherapy

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Abstract

Preoperative chemoradiotherapy (PCRT) is a standard treatment for locally advanced rectal cancer. The influence of PCRT on anorectal function has not been objectively assessed. We evaluated the short-term influence of PCRT on anorectal function in patients with locally advanced rectal cancer using anorectal manometry. We included 310 patients with locally advanced mid and lower rectal cancer who underwent PCRT from 2012 to 2015. We compared anorectal function based on anorectal manometry between before and after PCRT according to tumor location, clinical T (cT) stage, and tumor response after PCRT. Lower rectal cancer was common in the cohort of 310 patients ( n = 228, 73.5%). Sphincter length ( p = 0.003) and maximal resting pressure ( p < 0.001) increased and maximal tolerated volume ( p = 0.036) decreased after PCRT regardless of tumor location. Maximal squeezing pressure and rectal compliance slightly decreased, without statistical significance. Changes in manometric parameters after PCRT were not associated with changes of cT stage after PCRT. However, minimal sensory volume ( p = 0.042) and maximal tolerated volume ( p = 0.025) increased significantly in 143 patients (46.1%) with changes in the distance of the cancer from the anal verge after PCRT. PCRT did not impair the overall short-term anorectal manometric parameters in patients with locally advanced rectal cancer. Further study is required to investigate postoperative anorectal function after sphincter-preserving surgery to evaluate the long-term effects of PCRT on anorectal function.

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Most cited references 17

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Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.

S. T. Martin, H Heneghan, D. C. Winter (2012)

Following neoadjuvant chemoradiotherapy (CRT) and interval proctectomy, 15-20 per cent of patients are found to have a pathological complete response (pCR) to combined multimodal therapy, but controversy persists about whether this yields a survival benefit. This systematic review evaluated current evidence regarding long-term oncological outcomes in patients found to have a pCR to neoadjuvant CRT. Three major databases (PubMed, MEDLINE and the Cochrane Library) were searched. The systematic review included all original articles reporting long-term outcomes in patients with rectal cancer who had a pCR to neoadjuvant CRT, published in English, from January 1950 to March 2011. A total of 724 studies were identified for screening. After applying inclusion and exclusion criteria, 16 studies involving 3363 patients (1263 with pCR and 2100 without) were included (mean age 60 years, 65·0 per cent men). Some 73·4 per cent had a sphincter-saving procedure. Mean follow-up was 55·5 (range 40-87) months. For patients with a pCR, the weighted mean local recurrence rate was 0·7 (range 0-2·6) per cent. Distant failure was observed in 8·7 per cent. Five-year overall and disease-free survival rates were 90·2 and 87·0 per cent respectively. Compared with non-responders, a pCR was associated with fewer local recurrences (odds ratio (OR) 0·25; P = 0·002) and less frequent distant failure (OR 0·23; P < 0·001), with a greater likelihood of being alive (OR 3·28; P = 0·001) and disease-free (OR 4·33, P < 0·001) at 5 years. A pCR following neoadjuvant CRT is associated with excellent long-term survival, with low rates of local recurrence and distant failure. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer.

Matthew F Kalady, Luiz Felipe de Campos-Lobato, Luca Stocchi … (2009)

This study evaluates factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiation for rectal cancer. Approximately 20% of rectal cancer patients undergoing neoadjuvant chemoradiation achieve pCR, which has been associated with decreased local recurrence and improved recurrence-free survival. Means of predicting pCR remain incompletely defined. A total of 306 consecutive patients with stage II or stage III rectal cancer who underwent neoadjuvant chemoradiation then surgery between 1997 and 2007 were identified from a single-institution. Sixty-four patients with concurrent inflammatory bowel disease, hereditary colorectal cancer, other malignancy, urgent surgery, incomplete chemoradiation, or insufficient data were excluded. All patients received neoadjuvant 5-FU-based chemotherapy and external beam radiation. Histologic response was categorized as pCR or not-pCR, which defined the 2 study cohorts. Variables were analyzed by univariate and multivariate analysis with pCR as the dependent variable. Fisher exact test, chi2, Wilcoxon rank-sum, and logistic regression were used for analysis. P < 0.05 was considered statistically significant. Of the total patients, 242 were studied, including 58 (24%) that achieved pCR. The 2 groups were statistically similar in terms of age, gender, body mass index, tumor differentiation, radiation dose, and pretreatment stage. On multivariate analysis, an interval ≥ 8 weeks between treatment completion and surgical resection was significantly associated with a higher rate of pCR, which correlated with decreased local recurrence and improved overall survival. Despite traditional beliefs that certain patient and tumor factors influence pCR, an extended interval between completion of neoadjuvant therapy and surgery was the single most important determinant in achieving a pCR.

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Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome.

Paola Toppan, Mario Lise, Valentina Russo … (2004)

The aim of this study was to evaluate factors associated with pathologic tumor response following pre-operative chemoradiation therapy, and the prognostic impact of pathologic response on overall and disease-free survival. Between 1994 and 2002, 132 patients underwent chemoradiation therapy followed by surgery for middle to lower rectal cancer. After excluding 26 cases (metastatic cancer, n = 13; nonradical surgery, n = 6; local excision procedure, n = 4; non-5-fluorouracil-based chemotherapy, n = 2; incomplete data on preoperative chemoradiation therapy regimen used, n = 1), the remaining 106 patients were included in the study. Variables considered were the following: age, gender, tumor location, pretreatment T and N stage, modality of 5-fluorouracil administration, total radiotherapy dose delivered, chemoradiation therapy regimen used (Regimen A: chemotherapy (bolus of 5-fluorouracil and leucovorin, days 1-5 and 29-33) + radiotherapy (45 Gy/25 F/1.8 Gy/F); Regimen B: chemotherapy (5-fluorouracil continuous venous infusion +/- weekly bolus of carboplatin or oxaliplatin) + radiotherapy (50.4 Gy/28 F/1.8 Gy/F)), time interval between completion of chemoradiation therapy and surgery, postoperative chemotherapy administration, surgical procedures, pT, pN, and pTNM stage, and response to chemoradiation therapy defined as tumor regression grade, scored from 1 (no tumor on surgical specimen) to 5 (absence of regressive changes). Statistical analysis was performed by means of logistic regression analysis (Cox's model for overall and disease-free survival). Median age of the 106 patients was 60 (range, 31-79) years and the male:female ratio, 66:40. Median distance of tumor from the anal verge was 6 (range, 1-11) cm. Pretreatment TNM stage, available in 104 patients, was cT3T4N0, n = 41; cT2N1, n = 9; cT3N1, n = 39; and cT4N1, n = 17. The median radiotherapy dose delivered was 50.4 (range, 40-56) Gy; 58 patients received 5-fluorouracil by continuous venous infusion, and carboplatin with oxaliplatin was added to the chemotherapy schedule in 71 cases. Patients were given Regimen A in 47 cases and Regimen B in 59. The median interval between chemoradiation therapy and surgery was 42.5 (range, 19-136) days, and 94 patients underwent a sphincter-saving procedure. Tumor regression grade, available in 104 cases, was 1, n = 19; 2, n = 18; 3, n = 15; 4, n = 13; and 5, n = 39. At a median follow-up of 42 (range, 1-110) months, 11 patients had died, and 95 were alive. None of the patients had local recurrences, but 13 had distant recurrences. At logistic regression analysis, the chemoradiation therapy regimen used was the only independent predictor of tumor response following preoperative chemoradiation therapy (odds ratio = 0.29, 95% confidence interval = 0.13-0.67, P = 0.003). At Cox's regression analysis, pretreatment T stage was the only independent prognostic factor for both disease-free survival (relative risk = 7.13, 95% confidence interval = 2.3-21.8, P = 0.001) and overall survival (relative risk = 4.83, 95% confidence interval = 1.1-19.9, P = 0.029). Tumor response following preoperative chemoradiation therapy is mainly related to the preoperative regimen used. For patients receiving preoperative chemoradiation therapy, pretreatment T stage, but not tumor response to preoperative chemoradiation therapy, is prognostic for outcome (both disease-free and overall survival).

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Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 3 October 2017

Publication date (Electronic): 27 August 2017

Volume: 8

Issue: 45

Pages: 79982-79990

Affiliations

¹ Department of Colorectal Clinic, Asan Medical Center, Seoul, Korea

² Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

³ Department of Clinical Nursing, University of Ulsan, Seoul, Korea

Author notes

Correspondence to : In Ja Park, ipark@ 123456amc.seoul.kr

Jeong Hye Kim, kimjh@ 123456amc.seoul.kr

Article

Publisher ID: 20567

DOI: 10.18632/oncotarget.20567

PMC ID: 5668113

PubMed ID: 29108380

SO-VID: 65da13c4-98ce-4bea-9933-5074f315accd

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This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 29 March 2017

Date accepted : 15 August 2017

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Peri-treatment change of anorectal function in patients with rectal cancer after preoperative chemoradiotherapy

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Most cited references 17

Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.

Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer.

Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome.

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