Cheng, Jyi Ng

Objective: To develop a predictive model for pathological complete response (pCR) after total neoadjuvant therapy (TNT) to inform selection for watch-and-wait (W/W). Summary Background Data: Patient selection for W/W after TNT for locally advanced rectal cancer remains challenging. Methods: An ensemble of tabular foundation models was fine-tuned in adults with clinical stage II or III microsatellite stable primary rectal adenocarcinoma undergoing TNT and total mesorectal excision (TNT+TME) from 2018-2023 to predict pCR, using pre-TNT, post-TNT and pre-TME variables. This model was externally validated on patients having TNT and W/W (TNT+W/W) to predict persistent clinical complete response (pcCR; the absence of local regrowth, distant metastases, or persistent near-cCR). Area under the receiver operator curve (AUROC), area under the precision-recall curve (AUPRC), and Brier score were calculated with 95% confidence intervals (CI). Results: Among 308 patients that underwent TNT+TME (median age 56; 40% female), the model predicted pCR with an AUROC 0.71 (95% CI 0.65-0.77), AUPRC 0.44 (95% CI 0.35-0.57), and was well calibrated with a Brier score of 0.17 (95% CI 0.15-0.20). At external validation in a cohort of 83 patients that are being managed with TNT+W/W (median age 57; 37% female), the model predicted pcCR with an AUROC 0.69 (95% CI 0.57-0.82), AUPRC 0.90 (95% CI 0.82-0.96), and Brier score of 0.30 (95% CI 0.26-0.33), improving to 0.17 with recalibration. Conclusions: This novel predictive model demonstrated good discrimination and calibration for pCR after TNT+TME with utility in TNT+W/W for pcCR after appropriate recalibration, supporting its application for W/W patient selection.

Importance Tumor deposits have prognostic value in colon cancer, but the current American Joint Committee on Cancer (AJCC) staging only considers them if there are no concurrent positive lymph nodes. Objective To devise a staging system for colon cancer by integrating counts of tumor deposits with positive lymph nodes while retaining the current AJCC staging framework. Design, Setting, and Participants This retrospective cohort study examines data from a large-volume, tertiary care center database (January 2010 through March 2023 with follow-up until December 2023) and the population-based National Cancer Database (January 2010 through December 2020 with follow-up until December 2021). Participants were adults (age 18-75 years) with stage III colon adenocarcinoma who underwent chemotherapy, and had a specified positive lymph node count and tumor deposit count were selected. Exposure A real positive lymph nodes count was developed and used to derive Sassun-Mayo N/tumor, lymph node, and metastasis (TNM) stages that were compared with the AJCC N/TNM stages. Main Outcomes and Measures Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses for 3-year overall survival were performed to assess the efficiency of the 2 staging systems. The concordance index was used for validation using the National Cancer Database. Results From a total patient number of 11 162 (institutional) and 848 704 (national), the final patient numbers were 788 and 77 790, respectively. The institutional database patients had a mean (SD) age of 58.5 (11.5) years; there were 433 male patients (54.9%) and 355 female (45.1%). The national database patients had a mean (SD) age of 59.3 (10.6) years; there were 40 315 male patients (51.8%) and 37 475 female (48.2%). ROC curve areas were improved using the Sassun-Mayo stages (3-year death for AJCC TMN, 0.63 [95% CI, 0.57-0.69] vs 0.66 [95% CI, for 0.60-0.72] for Sassun-Mayo TNM). Kaplan-Meier curves revealed visible overlaps among AJCC N stages, which were absent in the Sassun-Mayo N stages. The concordance index in the Sassun-Mayo N/TNM stages was 0.611 and 0.616, respectively, while in the AJCC N/TNM stages, it was 0.598 and 0.606, respectively. Patients upstaged from N1 to N2 (n = 10 307; 13.2%) had a 3-year overall survival rate nearly identical to that of AJCC N2a patients. Additionally, 3001 patients (3.9%) were upstaged from N2a to N2b, indicating that 13 308 patients (17.1%) with stage III colon cancer across cohorts were understaged. Conclusions and Relevance This study found that Sassun-Mayo N/TNM staging provided superior overall survival stratification compared with the current AJCC staging, suggesting that their implementation could improve prognostication in colon cancer.

AbstractAimMinimally invasive transanal platforms are now the standard of care for select low‐risk rectal tumours. However, existing platforms come with persistent technical challenges. The da Vinci SP Surgical System™ offers a new alternative designed to work effectively in narrow spaces. This technology has the potential to enhance the feasibility and proximal extent of complex transanal resections. This study aimed to describe the morbidity and technical success in patients undergoing single‐port robotic transanal minimally invasive surgery (SPR‐TAMIS). Secondary outcomes include rates of local recurrence.MethodsA retrospective analysis was conducted on all patients who underwent SPR‐TAMIS at our institution between February 2019 and December 2023.ResultsThe study included 31 patients (19 men, 12 women) with a mean age of 61 ± 13.3 years. The average tumour distance from the anal verge was 10 cm. Thirty patients completed SPR‐TAMIS, with one patient requiring conversion to robotic sigmoidectomy due to location in the mid‐sigmoid colon. The mean operating time was 106 ± 42 min. Twenty‐eight out of 30 patients underwent full‐thickness excision and all but two were successfully closed. All specimens were resected intact, and margins were negative in 93.5% of cases. The average tumour size was 13 ± 34 cm2, with 13 lesions classified as adenomas and 16 as adenocarcinomas. All patients who did not undergo associated procedures were discharged on the day of surgery. Two patients experienced 30‐day morbidity. At a mean follow‐up of 18 months (± 13), no local or systemic recurrences were identified.ConclusionSPR‐TAMIS for excision of low‐risk rectal tumours is associated with high rates of technical success and low 30‐day morbidity. Further research is needed to compare SPR‐TAMIS with other techniques to determine potential advantages over current transanal platforms.