(UroToday.com) The 2023 GU ASCO annual meeting included a session on biomarkers of response and risk stratification in genitourinary cancers, featuring a presentation by Dr. Robert Hamilton discussing work from the European Association of Urology Testicular Cancer Guidelines Panel, specifically a new prognostic factor risk group classification for patients with clinical stage 1 seminoma in active surveillance. Indeed, between 4%- 30% of patients with clinical stage 1 seminoma testis in active surveillance relapse depending on pathological risk factors, such as tumor size (>4 cm) and rete testis invasion.1 The level of evidence supporting these pathological risk factors in clinical decision-making is low due to heterogeneous study design and reporting, as well as difficulty analyzing patient subgroups according to combination of these factors. The objectives of the present study were to identify the most important pathological prognostic factors predicting relapse in clinical stage 1 seminoma patients with normal post-orchidectomy serum tumor marker levels in active surveillance and to construct risk groups for guiding treatment decision-making and follow-up.
Individual patient data from 1,016 clinical stage 1-seminoma testis patients diagnosed between February 1994 and January 2019 in active surveillance were collected from nine institutions. Central pathology review was not routinely performed in all institutions, thus, pagetoid and stromal rete testis invasion were not differentiated explicitly in most cases. Assessing patient age, pre-orchidectomy serum tumor marker b-human chorionic gonadotropin and lactate dehydrogenase, pathological tumor size, rete testis invasion, lympho-vascular invasion, multi-focality, and GCNIS, multivariable Cox proportional hazards regression models were fit to identify the most important prognostic factors for the time to first relapse by imaging and/or markers (primary endpoint). Probabilities of relapse were estimated using Kaplan-Meier curves.
The baseline characteristics of the 1,016 patients is as follows:
After a median follow-up of 7.7 years, 149 (14.7%) patients relapsed, 104 were identified by imaging alone, 44 by imaging with elevated serum tumor markers, and 1 by elevated serum tumor markers alone. Overall 144/149 (97%) relapses occurred in the retroperitoneal nodes. Excluding 18 patients with unknown lympho-vascular invasion from the multivariable analyses, tumor size (≤ 2 cm, between 2 and 5 cm, > 5 cm), presence of rete testis invasion and presence of lympho-vascular invasion were used to form three risk groups: very low, low and high-risk:
Five-year probability of relapse varied from 8% in the very low risk-group to 44% in the high risk-group. Dr. Hamilton emphasized that 97% of patients fall into either the low or very-low risk groups:
The new model outperformed the current model with tumor size < 4 cm vs ≥ 4 cm and rete testis invasion (Harrell's C index 0.65 vs 0.61) and identifies a subgroup of patients with a higher risk of relapse:
Among 149 relapses, 68 (46%) were treated with chemotherapy and 80 (54%) were treated with radiation therapy. Of the 11 deaths, none were from testicular cancer and only one was from treatment toxicity.
Dr. Hamilton concluded his presentation discussing work from the European Association of Urology Testicular Cancer Guidelines Panel, specifically a new prognostic factor risk group classification for patients with clinical stage 1 seminoma in active surveillance with the following concluding messages:
- Relapse in stage I seminoma on surveillance is rare: 14.7% in this cohort
- Outcomes after relapse are excellent: >99% cancer-specific survival
- The new risk stratification model performed better than the traditional model: tumor size (<2 cm, 2-5 cm, >5 cm), rete testis invasion, and lymphovascular invasion
- The majority (~97%) of men fall into “very low” or “low” risk of relapse
- A small subset (3%) have higher risk of relapse (44% at 5 years), which may warrant a discussion of adjuvant therapy options
Presented by: Robert J. Hamilton, MD, MPH, FRCSC, University Health Network, University of Toronto, Toronto, ON, Canada
Co-Authors: Joost Boormans, Richard J Sylvester, Lynn Anson-Cartwright, Rachel Glicksman, Gedske Daugaard, Jakob Lauritsen, Thomas Wagner, Barbara Avuzzi, Nicola Nicolai, Jorge Aparicio, Xavier Garcia del Muro, Pilar Laguna
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:
- Warde P, Specht L, Horwich A, et al. Prognostic factors for relapse in stage I seminoma managed by surveillance: A pooled analysis. J Clin Oncol. 2002 Nov 15;20(22):4448-4452.