Pathological response calculation assessment remains accurate with reduced tumor bed examination after neoadjuvant immunotherapy in clinically detectable stage III melanoma

Authors/Creators

• R. V. Rawson
• N. G. Maher
• A. M. Menzies
• S. N. Lo
• N. Mesbah Ardakani
• L. A. Jackett
• I. A. Vergara
• T. E. Pennington
• K. F. Shannon
• S. Ch’ng
• M. Gonzalez
• E. M. Burton
• M. W. Lucas
• I. L.M. Reijers
• E. A. Rozeman
• D. E. Gyorki
• S. Sandhu
• M. S. Carlino
• J. Howle
• M. Khattak, Edith Cowan UniversityFollow
• A. Van der Westhuizen
• M. C. Andrews
• V. Atkinson
• A. C.J. van Akkooi
• A. J. Spillane
• R. P.M. Saw

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 (R²> 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.

Keywords

Melanoma, neoadjuvant, pathological response, tumor bed

Document Type

Journal Article

Date of Publication

2-1-2026

Volume

37

Issue

2

PubMed ID

41183783

Publication Title

Annals of Oncology

Publisher

Elsevier

School

School of Medical and Health Sciences

Funders

Australian Government / Melanoma Institute Australia / Australian Melanoma Research Foundation (1263669) / National Health and Medical Research Council / Sydney Medical Foundation

Grant Number

NHMRC Numbers : GNT2009476, GNT2034195, 2021/GNT2007839, 2022/GNT2018514

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Comments

Rawson, R., Maher, N., Menzies, A., Lo, S., Ardakani, N. M., Jackett, L., Vergara, I., Pennington, T., Shannon, K., Ch’ng, S., Gonzalez, M., Burton, E., Lucas, M., Reijers, I., Rozeman, E., Gyorki, D., Sandhu, S., Carlino, Howle, J., . . . Scolyer, R. (2025). Pathological response calculation assessment remains accurate with reduced tumor bed examination after neoadjuvant immunotherapy in clinically detectable stage III melanoma. Annals of Oncology, 37(2), 206–216. https://doi.org/10.1016/j.annonc.2025.10.1237

First Page

206

Last Page

216