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Long-term outcomes of surgery alone versus surgery following preoperative chemoradiotherapy for early T3 rectal cancer: A propensity score analysis.

ABSTRACT: Recently, a few studies have raised the question of whether preoperative chemoradiotherapy (PCRT) is essential for all T3 rectal cancers. This case-matched study aimed to compare the long-term outcomes of surgery alone with those of PCRT?+?surgery for magnetic resonance imaging (MRI)-assessed T3ab (extramural depth of invasion ?5?mm) and absent mesorectal fascia invasion (clear MRF) in mid/lower rectal cancer patients.From January 2006 to November 2012, 203 patients who underwent curative surgery alone (n?=?118) or PCRT?+?surgery (n?=?85) were enrolled in this retrospective study. A 1:1 propensity score-matched analysis was performed to eliminate the inherent bias. Case-matching covariates included age, sex, body mass index, histologic grade, carcinoembryonic antigen, operation method, follow-up period, tumor height, and status of lymph node metastasis. The end-points were the 5-year local recurrence (LR) rate and disease-free-survival (DFS).After propensity score matching, 140 patients in 70 pairs were included. Neither the 5-year LR rate nor the DFS was significantly different between the 2 groups (the 5-year LR rate, P?=?0.93; the 5-year DFS, P?=?0.94). The 5-year LR rate of the surgery alone was 2% (95% confidence interval [CI] 0.2%-10.9%) versus 2% (95% CI 0.2%-10.1%) in the PCRT?+?surgery group. The 5-year DFS of the surgery alone was 87% (95% CI 74.6%-93.7%) versus 88% (95% CI 77.8%-93.9%) in the PCRT?+?surgery group.In patients with MRI-assessed T3ab and clear MRF mid/lower rectal cancer, the long-term outcomes of surgery alone were comparable with those of the PCRT?+?surgery. The suggested MRI-assessed T3ab and clear MRF can be used as a highly selective indication of surgery alone in mid/lower T3 rectal cancer. Additionally, in those patients, surgery alone can be tailored to the clinical situation.

SUBMITTER: Cho SH

PROVIDER: S-EPMC5371457 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Long-term outcomes of surgery alone versus surgery following preoperative chemoradiotherapy for early T3 rectal cancer: A propensity score analysis.

Cho Seung Hyun SH Choi Gyu-Seog GS Kim Gab Chul GC Seo An Na AN Kim Hye Jung HJ Kim Won Hwa WH Shin Kyung-Min KM Lee So Mi SM Ryeom Hunkyu H Kim See Hyung SH

Medicine 20170301 12

Recently, a few studies have raised the question of whether preoperative chemoradiotherapy (PCRT) is essential for all T3 rectal cancers. This case-matched study aimed to compare the long-term outcomes of surgery alone with those of PCRT + surgery for magnetic resonance imaging (MRI)-assessed T3ab (extramural depth of invasion ≤5 mm) and absent mesorectal fascia invasion (clear MRF) in mid/lower rectal cancer patients.From January 2006 to November 2012, 203 patients who underwent curative surger ...[more]

PMID: 28328820

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Project description:BackgroundDistant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine.MethodsBetween 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared.ResultsA total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared.ConclusionsTriweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.

Project description:PurposeAlthough adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT versus that of postoperative CRT for resectable or potentially resectable gastric cancer.MethodsFrom January 2005 to December 2017, patients with clinical stage III/IVa (i.e., T3-4aN+M0 or T4bNxM0) locally advanced gastric cancer were retrospectively identified. Survival after preoperative CRT and postoperative CRT was assessed by unadjusted, propensity score matching (PSM) and inverse probability of treatment weight (IPTW) analyses. Moreover, exploratory subgroup analyses were performed, and toxicity and patterns of failure were also investigated.ResultsThe median follow-up time was 32.5 months. A total of 82 and 463 patients were enrolled in the preoperative and postoperative CRT groups, respectively. After propensity score matching, preoperative CRT was associated with improved overall survival (OS) and disease-free survival (DFS) compared with postoperative CRT (3-year OS: 72.6 vs. 54.4%, log-rank p = 0.0021; 3-year DFS: 61.7 vs. 44.7%, log-rank p = 0.002). The unadjusted and IPTW analyses yielded consistent results. A complete pathologic response was achieved in 13.4% of the preoperative CRT group. Although the incidence of grade 3 or 4 adverse effects and surgical complications were similar between the two groups, significantly fewer patients experienced treatment interruptions or dose reductions due to toxic effects in the preoperative CRT setting than in the postoperative CRT setting (3.7 vs. 10.6%, p = 0.049).ConclusionsCompared with postoperative CRT, preoperative CRT was associated with improved OS and DFS, superior treatment compliance and comparable surgical complications for patients with locally advanced gastric cancer. Our findings provide important evidence for the optimal combination modalities of surgery and CRT in the absence of randomized clinical data.

Project description:ImportanceDistant recurrence following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma is common. Adjuvant chemotherapy may improve survival.ObjectiveTo compare adjuvant chemotherapy with postoperative observation following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma.Design, setting, and participantsPropensity score-matched analysis using the National Cancer Database. We included adult patients who received a diagnosis between 2006 and 2013 of clinical stage T1N1-3M0 or T2-4N0-3M0 adenocarcinoma of the distal esophagus or gastric cardia who were treated with preoperative chemoradiotherapy and curative-intent resection. Patients receiving adjuvant chemotherapy were matched by propensity score to patients undergoing postoperative observation.ExposuresAdjuvant chemotherapy and postoperative observation.Main outcomes and measuresOverall survival.ResultsWe identified 10?086 patients (8840 [88%] male; mean [SD] age, 61 [9.5] years), 9272 in the postoperative observation group and 814 in the adjuvant chemotherapy group. Patients receiving adjuvant chemotherapy were younger (18-54 years: 252 [31%] vs 1989 [21%]; P?<?.001) and were more likely to have advanced disease (ypT3/4: 458 [62%] vs 3531 [46%]; P?<?.001; ypN+: 572 [72%] vs 3428 [39%]; P?<?.001), as well as shorter postoperative inpatient stays (>2 weeks: 94 [13%] vs 1589 [20%]; P?<?.001). A total of 732 patients in the adjuvant chemotherapy group were matched by propensity score to 3660 patients in the postoperative observation group. Adjuvant chemotherapy was associated with improved overall survival compared with postoperative observation (median survival: 40 months; 95% CI, 36-46 months vs 34 months; 95% CI, 32-35 months; stratified log-rank P?<?.001; hazard ratio, 0.79; 95% CI, 0.72-0.88). Overall survival at 1, 3, and 5 years was 88%, 47%, and 34% in the observation group, and 94%, 54%, and 38% in the adjuvant chemotherapy group, respectively. Adjuvant chemotherapy was associated with a survival benefit compared with postoperative observation in most patient subgroups.Conclusions and relevanceFor patients with locally advanced gastroesophageal adenocarcinoma treated with preoperative chemoradiotherapy and resection, adjuvant chemotherapy was associated with improved overall survival. Our findings have important implications for the postoperative treatment of this patient group for which few data are available.

Project description:BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement.MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups.ResultsA total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46-87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p<0.001).ConclusionUsing MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.

Project description:The incorporation of chemoradiation prior to resection of the tumour has revolutionized the management of locally advanced rectal cancer. However, a large proportion of these patients are resistant to preoperative treatment schedule. We recently reported that c-Myc gene expression correlates negatively with this resistance in patients with rectal cancer. In this study, we carried out integrated analysis of miRNA and mRNA expression profiling in 45 pre-treatment rectal tumour. Further, expression of miRNAs and c-Myc, and their relationship with clinicopathological factors and patient survival was analysed. As a result, we found that 12 miRNAs were differentially expressed between responder and non-responder rectal cancer patients. Functional classification revealed an association between differentially expressed miRNAs and c-Myc. Subsequent quantitative real-time PCR results showed that both, miRNA-148 and miRNA-375 levels were significantly lower in responder compared to non-responder patients. Notably, the higher level of miRNA-375 was significantly negatively correlated with c-Myc. These results suggest that miRNA-375 and its targeted c-Myc play an important role as predictive biomarker of response to neoadjuvant treatment in patients with locally advanced rectal cancer, but still not suitable for prognosis. Pre-treatment biopsies of 22 patients with LARC were prospectively collected and freshly frozen according to an institutional board-approved protocol. Tumour response was assessed in surgical specimens by pathological examination based on the semi-quantitative tumour regression grading (TRG) system described by Mandard in 1994[36]: TRG1 and TRG2 scores were considered responders, whereas TRG3, TRG4, and TRG5 were classified as non-responders. The inclusion criteria were: histologically proven rectal tumour at a clinical stage UICC II-III (cT3-4/and or N positive), following endorectal ultrasound and/or MRI scan. Patients were excluded if they had the tumour located above 13 cm from the anal verge by rigid rectoscopy, synchronic colonic cancer assessed by colonoscopy, distant metastases by 18FDG PET-CT scan, and suspicion of hereditary colorectal cancer. All patients subsequently received a total dose of 50.4Gy of radiation (28 fractions of 1.8Gy) associated with capecitabine (oral form of 5-FU) with or without oxaliplatine, according to our Hospital Clinical Practice Guidelines. Standardized Surgery was performed, including total mesorectal excision, following an interval of 8-10 weeks after completion of CT/RT.

Dataset Information

Long-term outcomes of surgery alone versus surgery following preoperative chemoradiotherapy for early T3 rectal cancer: A propensity score analysis.

Publications

Long-term outcomes of surgery alone versus surgery following preoperative chemoradiotherapy for early T3 rectal cancer: A propensity score analysis.

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