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ESMO 2022

ESMO 2022: Biopsy-Based Basal-Luminal Subtyping Classifier in High-Risk Prostate Cancer: Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Randomized Phase III Trials

(UroToday.com) In the Prostate Cancer poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Paul Nguyen presented analysis of three NRG Oncology/RTOG clinical trials aimed at assessing the predictive role of basal-luminal subtyping for the duration of androgen-deprivation therapy in high-risk prostate cancer. To date, sub-type differentiation in prostate cancer has demonstrated both prognostic and predictive ability for ADT response in the post-operative setting. In this analysis, the authors sought to assess whether gene expression profiling of pre-treatment samples would predict the benefit of long (24-28 month) as compared to short (4 month) duration of ADT. The authors presupposed that patients with basal tumor would derive greater benefit from longer durations of ADT.

The authors performed whole-transcriptome arrays of biopsy samples from patients enrolled in three NRG/RTOG randomized phase III trials (9202, 9413, and 9902). The prognostic and predictive ability of a 215 gene basal-luminal prostate subtyping classifier (PSC) was evaluated while examining a number of endpoints including biochemical failure (BF), distant metastasis (DM), metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and overall survival (OS). The authors used multivariable Cox models (MVA). Event rates were estimated by the cumulative incidence method and compared with Gray’s or logrank tests.

Across these three trials, the authors analysed 265 samples of which 40% were PSC basal and 60% were luminal.

kaplan_meier_plots_comparing_basal_luminal_overall_prognosis_image_1.jpg 

In a multivariable analysis, the PSC basal subtype had a worse prognosis compared to PSC luminal for nearly all endpoints including MFS (HR [95% CI] 1.8 [1.3-2.5], p<0.001), PCSM (HR 2.8 [1.5-5.0], p<0.001), and OS (HR 1.8 [1.3-2.6], p<0.001). In absolute terms, PCSM rates at 10 years were 26% (95% CI 17-35%) for basal vs 11% (6-15%) for luminal subtypes.

A significant interaction between PSC and ADT duration was observed for both biochemical failure (p=0.02) and PCSM (p=0.007). Similar but non-significant trends were observed for DM, MFS, and OS. Basal subtypes significantly benefitted from LT- vs STADT (10-year PCSM 5% [95% CI 0-11%] vs 42% [29-56%], p<0.001), while luminal outcomes did not differ by ADT duration (p=0.72).

pcsm_cumulative_incidence_by_psc_length_of_hormone_therapy_image_2 

Thus, Dr. Nguyen concluded that a gene expression analysis of pretreatment biopsy samples from three NRG phase III trials of high-risk PCa suggests that basal-luminal subtyping is predictive for the benefit of long-term vs short-term ADT. In particular, patients with basal tumors benefitted from longer-term ADT while those with luminal did not. As a result, this assay may allow for personalization of ADT prescribing in patients with high-risk prostate cancer.

Presented by: Paul L. Nguyen, MD, Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA



Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.