Pathological response calculation assessment remains accurate with reduced tumor bed examination after neoadjuvant immunotherapy in clinically detectable stage III melanoma
- Author(s)
- Rawson, RV; Mesbah Ardakani, N; Maher, NG; van der Westhuizen, A; Menzies, AM; Lo, SN; Jackett, LA; Vergara, IA; Pennington, TE; Shannon, KF; Ch'ng, S; Gonzalez, M; Burton, EM; Lucas, MW; Reijers, ILM; Rozeman, EA; Gyorki, DE; Sandhu, S; Carlino, MS; Howle, J; Khattak, M; Andrews, MC; Atkinson, V; van Akkooi, ACJ; Spillane, AJ; Saw, RPM; van de Wiel, BA; Blank, CU; Long, GV; Tetzlaff, MT; Scolyer, RA;
- Details
- Publication Year 2026-02,Volume 37,Issue #2,Page 206-216
- Journal Title
- Annals of Oncology
- Publication Type
- Research article
- Abstract
- BACKGROUND: Neoadjuvant immunotherapy produces event-free survival advantage over adjuvant therapy for patients with surgically resectable macroscopic stage IIIB/C/D melanoma. Pathological response, determined as percentage residual viable tumor (% RVT), provides critical prognostic information and informs management decisions. Here, we assessed accuracy of %RVT calculation when reduced tumor bed (TB) was examined and leverage these results proposing streamlined protocols for pathological examination. PATIENTS AND METHODS: Comprehensive histopathological examination was carried out on 134 patient specimens after neoadjuvant immunotherapy with ipilimumab and nivolumab. Impact on %RVT when evaluating less TB than recommended by the initial International Neoadjuvant Melanoma Consortium (INMC) protocol was assessed. Firstly, % RVT of each case was recalculated using seven modified protocols and compared with % RVT obtained under INMC protocol. Next, a simulation study was carried out recalculating % RVT by random sampling 50%, 33%, and 25% of TB slides per specimen. RESULTS: There was excellent accuracy in %RVT (R(2) > 0.97) for all the modified protocols and >90% accuracy in five protocols. Accuracy of major pathological response (MPR)/non-MPR and pathological response category classification was ≥96% in six protocols. The decrease in average slides examined per specimen ranged from 9% to 58%. In total, 85%, 79%, and 74% of simulations recalculating %RVT were within 5% of the INMC calculation when 50%, 33%, and 25% of TB slides were examined, respectively. If TB slide examination is capped at 20, %RVT calculation remains 93% accurate. CONCLUSIONS: TB embedded for histopathological examination in neoadjuvant stage IIIB/C/D melanoma specimens can be reduced without significantly compromising accuracy of %RVT calculation. We recommend an updated pathological assessment protocol: lymph nodes ≤3 cm examined in entirety; macroscopically involved lymph nodes >3 cm should have a modified examination protocol of at least a full cross-sectional transverse slice. Capping TB slides examined at 20 appears reasonable. This refined approach results in high accuracy and significant reduction in the slides examined.
- Publisher
- Elsevier
- Keywords
- Humans; *Melanoma/pathology/drug therapy/therapy/immunology; *Neoadjuvant Therapy/methods; Neoplasm Staging; Ipilimumab/administration & dosage; Nivolumab/administration & dosage; Female; Male; Middle Aged; *Skin Neoplasms/pathology/drug therapy; Neoplasm, Residual/pathology; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Prognosis; Immunotherapy/methods; Aged; Adult; melanoma; neoadjuvant; pathological response; tumor bed
- Department(s)
- Pathology; Medical Oncology; Surgical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.annonc.2025.10.1237
- Open Access at Publisher's Site
https://doi.org/10.1016/j.annonc.2025.10.1237- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-12-05 02:49:47
Last Modified: 2026-02-03 03:57:05