Pathological response calculation assessment remains accurate with reduced tumor bed examination following neoadjuvant immunotherapy in clinically detectable stage III melanoma
- Author(s)
- Rawson, RV; Maher, NG; Menzies, AM; Lo, SN; Ardakani, NM; 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; van der Westhuizen, A; Andrews, MC; Atkinson, V; van Akkooi, ACJ; Spillane, AJ; Saw, RPM; van de Wiel, BA; Blank, CU; Long, GV; Tetzlaff, MT; Scolyer, RA;
- Journal Title
- Annals of Oncology
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND: Neoadjuvant immunotherapy produces event-free survival advantage over adjuvant therapy for patients with surgically resectable macroscopic stage IIIB/C/D melanoma. Pathologic response, determined as % 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 histopathologic examination was performed on 134 patient specimens following neoadjuvant immunotherapy with ipilimumab and nivolumab. Impact on %RVT when evaluating less TB than recommended by initial International Neoadjuvant Melanoma Consortium (INMC) protocol was assessed. Firstly, %RVT of each case was recalculated using seven modified protocols and compared to %RVT obtained under INMC protocol. Next, a simulation study was performed 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%. 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 < 3cm examined in entirety; macroscopically involved lymph nodes >3cm 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 slides examined.
- Keywords
- Neoadjuvant; melanoma; pathological response; tumor bed
- Department(s)
- Pathology; Medical Oncology; Surgical Oncology
- Publisher's Version
- 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: 2025-12-05 02:55:47