Computational pathology-enabled residual tumor estimation as a predictor of survival in anal SCC
The incidence of anal squamous cell carcinoma has increased, and treatment has shifted from surgery to chemoradiotherapy, with salvage abdominoperineal resection reserved for persistent and recurrent cases. The authors conducted a study in which they evaluated the utility of various tumor-regression scoring systems in predicting survival in anal squamous cell carcinoma (SCC) patients, using pathologists’ observations and digital pathology. Data for cases managed surgically from 2005 to 2019 were collected. Residual tumor was assessed using multiple methods, such as by examining gross tumor size, largest focus of tumor on a hematoxylin-and-eosin (H&E)-stained slide, and average of residual tumor across all submitted H&E-stained slides. Assessment also used Japanese Esophageal Society, Chirieac, Schneider, Hermann, and College of American Pathologists scoring systems. For the study, three expert pathologists individually estimated, or eyeballed, the residual tumor percentage using a preselected representative H&E-stained slide. QuPath software was used to measure tumor volume on the same slide. American Joint Committee on Cancer eighth edition staging and outcome data were retrieved from electronic medical records. The study involved 48 participants who were predominantly female (56 percent) and a median age of 57 years. Most were Caucasian. Seventy-seven percent (17 of 22) of those assessed were human papillomavirus positive. Initial patient treatment included chemoradiotherapy followed by abdominoperineal resection (79 percent) or pelvic exenteration (21 percent). Complications (13 percent), persistent disease (33 percent), and recurrence (54 percent) led to surgical interventions. Fifty-one percent of patients had moderately differentiated SCC, and 42 percent had poorly differentiated disease. Lymphovascular invasion (44 percent), perineural invasion (38 percent), and lymph node metastasis (13 percent) were present. Distant metastasis was rare (two percent). Median overall survival was 3.2 years. Positive margins (hazard ratio [HR], 4.12; 95 percent confidence interval [CI], 1.83–9.28) and larger tumor size (HR, 1.02; 95 percent CI, 1.01–1.03) were associated with an increased hazard of death. Most residual tumor measurement methods were not significantly associated with overall survival. Interobserver agreement based on eyeballing was moderate (kappa, 0.4). Computational pathology-based residual tumor percentage was the only method significantly associated with outcome, with each 10 percent increase in residual tumor percentage corresponding to a 1.23-fold higher hazard of death (95 percent CI, 1.03–1.46; P=.024). This study highlights the important role of computational pathology in predicting outcomes in anal SCC treated with chemoradiotherapy and surgery. Specifically, computational assessment of the residual tumor percentage is a strong predictor of overall survival, outperforming other established tumor-regression scoring methods.
Toro P, Bakhshwin A, Zein-Sabatto B, et al. Computational pathology-enabled residual tumor estimation is a prognostic factor for overall survival in anal squamous cell carcinoma. Mod Pathol. 2025. doi.org/10.1016/j.modpat.2024.100692
Correspondence: Dr. Daniela S. Allende at allendd@ccf.org