Background: Neoadjuvant chemoradiotherapy is regarded as the standard of treatment for locally advanced lower rectal cancer although some of these cases are systemic, and local control may be inadequate. We aimed to stratify patients into prognostic groups based on preoperative factors, including response to neoadjuvant chemotherapy. Methods: We retrospectively analyzed patients with locally advanced lower rectal adenocarcinoma (clinical stage II/III with high-risk features of distant metastasis) who were treated with neoadjuvant chemotherapy followed by curative resection between 2010 and 2017 and those, who did not receive neoadjuvant chemoradiotherapy. Reduction in tumor volume (before vs. after neoadjuvant chemotherapy) was measured using magnetic resonance imaging. Recurrence and overall survival were also evaluated.Results: The cohort was composed of 105 patients. Good response to neoadjuvant chemotherapy was associated with better 5-year recurrence-free survival (good responders: 83.3%, poor responders: 50.9%; p=0.001) and 5-year overall survival (good responders: 95.8%, poor responders: 82.5%; p=0.04). In a multivariate analysis, extramural venous invasion on magnetic resonance imaging before neoadjuvant chemotherapy was significantly and independently associated with worse recurrence-free survival (hazard ratio: 2.57, 95% confidence interval: 1.32–5.03, p=0.006). Good responders without extramural venous invasion had the best 5-year recurrence-free and overall survival (89.7% and 94.9%, respectively). Poor responders with extramural venous invasion had the worst 5-year recurrence-free and overall survival (26.7% and 60.0%, respectively).Conclusions: Reductions in tumor volume after neoadjuvant chemotherapy were associated with better prognosis in patients with locally advanced lower rectal cancer. Extramural venous invasion was a preoperative prognostic factor.
108 Background: In VOLTAGE-A, CRT (50.4 Gy with capecitabine of 1,650 mg/m2) followed by five cycles of consolidation Nivo (240 mg q2 weeks [W]) and radical surgery showed 30% of pathological complete response (pCR) in pts with MSS and 60% in MSI-H T3–4 NanyM0 LARC. Here, we report survival outcomes and functional results. Methods: All 39 MSS and 5 MSI-H pts were included in the VOLTAGE-A from Jan 2017 to Oct 2019. Survival outcomes, late adverse events, and patient-reported outcome measurements for urogenital and anal functions were analyzed. Urinary function was evaluated using the International Prostate Symptom Score (I-PSS) periodically at 1W, 1, 3, 6, and 12 months (M), postoperatively. Sexual function in sexually active male pts was evaluated using the International Index of Erectile Function (IIEF) score at 3, 6, and 12M, postoperatively. Anal function was evaluated using the Wexner score, low anterior resection syndrome (LARS) score, and fecal incontinence severity index (FISI) score at 1-year post-surgery. All functional scores were evaluated preoperatively. Results: With a median follow-up of 44.8M (range, 25.7-58.9M), the 3-year relapse-free survival (RFS) and 3-year overall survival (OS) rates were respectively 79.5% and 97.4% in MSS, and 100% each in MSI-H pts. Of the MSS pts, those with pCR, clinical CR (cCR) according to the MSKCC criteria, high PD-L1 expression (tumor proportion score [TPS] ≥1%), and CD8/eTreg ratios of ≥2.5 had a trend of better 3-year RFS and OS than those without. During the follow-up period, one patient developed CTCAE grade 3 immune-related colitis, which was diagnosed 20M after the last dose of Nivo. Postoperative functional results were acceptable in both populations; pre-surgical median I-PSS scores were 3, whereas postsurgical values were 5 (1W), 5.5 (1M), 5 (3M), 4 (6M), and 4 (12M); median IIEF score was 20 at pre-surgery and 6 (3M), 6 (6M), and 8 (12M) at post-surgery; median scores of Wexner, LARS, and FISI were 2, 23, and 7 at pre-surgery, and 9, 30, and 17 at 1-year post-surgery, respectively. Conclusions: Preoperative CRT followed by Nivo showed promising survival outcomes in both MSS and MSI-H LARC pts. The therapeutic effect of pCR, cCR, and certain biomarkers analyzed by pre-CRT samples could be used as prognostic predictors in MSS pts. Clinical trial information: NCT02948348 .[Table: see text]
The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a in the eighth edition of the American Joint Committee on Cancer (AJCC)-TNM stage is subjective, and more objective discrimination method for deeply invasive advanced colon cancer is mandatory for standardized patient management. Peritoneal elastic laminal invasion (ELI) detected using elastic staining may increase the objective discrimination of deeply invasive advanced colon cancer. In this study, we constructed ELI study group to investigate feasibility, objectivity, and prognostic utility of ELI. Furthermore, pT classification using ELI was investigated based on these data. At first, concordance study investigated objectivity using 60 pT3 and pT4a colon cancers. Simultaneously, a multi-institutional retrospective study was performed to assess ELI’s prognostic utility in 1202 colon cancer cases from 6 institutions. In the concordance study, objectivity, represented by κ, was higher in the ELI assessment than in pT classification. In the multi-institutional retrospective study, elastic staining revealed that ELI was a strong prognostic factor. The clinical outcome of pT3 cases with ELI was significantly and consistently worse than that of those without ELI. pT classification into pT3 without ELI, pT3 with ELI, and pT4a was an independent prognostic factor. In this study, we revealed that ELI is an objective method for discriminating deeply invasive advanced colon cancer. Based on its feasibility, objectivity, and prognostic utility, ELI can subdivide pT3 lesions into pT3a (without ELI) and pT3b (with ELI).
TPS269 Background: Radical surgery is the standard treatment for advanced lower rectal cancer, but postoperative complications and sequelae are major problems. Recently, some patients treated with preoperative chemoradiotherapy (CRT) have been reported to achieve a clinical complete response (cCR) and be cured with a subsequent watch-and-wait strategy (W&W) without surgery. Moreover, the introduction of total neoadjuvant therapy (TNT) consisting of CRT and systemic chemotherapy has increased proportion of cCR. However, most previous studies on W&W have reported cases in which cCR was achieved incidentally as a result of preoperative CRT or TNT for advanced lower rectal cancer. It is unclear whether combining TNT that is highly effective in early stage rectal cancer and subsequent W&W without surgery is an effective intention-to-cure treatment for advanced lower rectal cancer when cCR is obtained after TNT. The purpose of this single-arm confirmatory trial is to evaluate the efficacy and safety of TNT and intended W&W for cT2-T3 advanced lower rectal cancer with a tumor diameter of 5 cm or less. Methods: Key eligibility criteria include low rectal adenocarcinoma with tumor diameter 5 cm or less, cT2 or cT3 tumor depth, no lymph node metastasis, no distant metastasis, no history of pelvic irradiation or rectal surgery, age 18-75 years, and sufficient organ function. Eligible patients are receiving TNT. CRT consists of the standard dose of capecitabine (1650 mg/m2/day) and radiotherapy (45 Gy/25 fractions to whole pelvis plus boost of 5.4 Gy/3 fractions to primary tumor). Consolidation chemotherapy consists of 4 courses of CAPOX (oxaliplatin 130 mg/m2 on day1 and capecitabine 2000 mg/m2/day on day1-14). After completing TNT, patients will be re-staged according to Memorial Sloan Kettering Cancer Center Criteria. Patients with cCR at the primary site will move to W&W, patients with a near complete response will move to either W&W or undergo local resection, and patients with an incomplete response will undergo total mesorectal excision. All patients will be followed every 3 months for 2 years after re-staging, and every 6 months for 3 years after that. The primary endpoint in phase II is the proportion of cCR at re-staging by central review and in phase III is 5-year overall survival (OS). In the phase II part, 40 patients were required with a one-sided alpha of 5%, power of 80%, a threshold value of 20%, and an expected value of 40%. Based on the results of previous studies, we set the threshold 5-year OS at 87% in the phase III part. The sample size was calculated as 105 including the phase II part with a one-sided alpha of 5%, power of 80%, and the expected 5-year OS of 95%. The first patient was enrolled in September 2022. Clinical trial information: jRCTs031220288 .
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