mCRPC Tumors Can Be Classified as Luminal and Basal, Helping to Guide Treatment Decisions

Article

Metastatic castration-resistant prostate cancer tumors can be classified as luminal and basal, possibly allowing for a better precision medicine approach to treatment.

After identifying that metastatic castration-resistant prostate cancer (CRPC) tumors can be classified as luminal and basal, investigators believe that more opportunities could open for personalizing treatment based on molecular findings, according to an article published in JAMA Oncology.

Findings from the study indicated that androgen signaling inhibitors (ASI) were found to be more effective in luminal tumors, and a chemotherapy approach should be considered for basal tumors. The median overall survival (OS) in those with basal tumors was 33.3 months vs 18.7 months for luminal tumors in those treated in the East Coast Dream Team (ECDT) cohort with 266 patients using poly-A enriched data with ASI post biopsy (ECDT HR, 0.39; 95% CI, 0.20-0.74; P = .004). Treatment with an ASI resulted in significantly better median survival for those with luminal tumors at 32.0 months vs 8.7 months for basal tumors (HR, 0.27; 95% CI, 0.14-0.53; P <.001). Moreover, patients who had basal tumors experienced a lower effect size that was no longer significant (HR, 0.62; 95% CI, 0.36-1.04; P = .07).

OS was examined in 80 patients in the ECDT cohort and 123 in the West Coast Dream Team (WCDT) cohort. Overall, only 19 patients in the WCDT cohort received chemotherapy for their disease prior to treatment enrollment. In the ECDT cohort, those with luminal tumors treated with ASI post-biopsy had better OS than those with basal tumors at 32.0 months vs 21.7 months (HR, 0.57; 95% CI, 0.33-0.97; P = .04), with no significant difference being found in those who were not treated with ASI post-biopsy.

The median OS in the ECDT cohort was 28.1 months vs the WCDT cohort of 25.7 months following treatment with post-biopsy ASI. When both cohorts were pooled for an interaction analysis, it was found that there was an interaction between subtype and post-biopsy ASI therapy (HR, 0.42; 95% CI, 0.20-0.89; P = .02). Of those who had never received ASI treatment, those with luminal tumors had a better OS than those with basal tumors (HR, 0.39; 95% CI, 0.20-0.74; P = .005), with similar interaction in the ASI-naïve subset (HR, 0.07; 95% CI, 0.01-0.48; P = .007).

A total of 634 metastatic CRPC samples were collected across 4 cohorts. A basal group was detected in 346 samples, and a luminal group in 288. Among the small cell/neuroendocrine prostate cancer (SCNC) samples, 53 were classified as basal.

The most luminal-enriched pathway was the androgen response pathway identified by the gene set enrichment analysis, as well as SCNC in basal tumors. Basal-enriched pathways were associated with cell cycle and cell division which is consistent with increased expression of proliferative genes including MKI67.

A higher rates of basal tumors were reported to have RB1 alterations (23%), compared with luminal tumors (4%; Fisher exact test; P <.001). There was no significant difference between PTEN mutation loss between patients with basal tumors (29%) and luminal tumors (32%; Fisher exact test; P = .45), or TP53 loss (33% vs 28%, respectively; Fisher exact test; P = .19). Higher alteration rates in FOXA1 were observed in the basal tumors cohort (36%) vs luminal tumors (27%; Fisher exact test; P = .03) and MYC (73% vs 56%, respectively; Fisher exact test; P <.001). However, there was no significant difference in androgen receptor pathways between the 2 groups (74% vs 79%; Fisher exact test; P = .22).

Reference

Aggarwal R, Rydzewski NR, Zhang L, et al. Prognosis associated with luminal and basal subtypes of metastatic prostate cancer. JAMA Oncol. 2021;7(11):1644-1652. doi:10.1001/jamaoncol.2021.3987

Related Videos
Anemia in patients who receive talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer appears to be manageable without any compromises in patient-reported outcomes and quality of life.
Artificial intelligence models may be “seamlessly incorporated” into clinical workflow in the management of prostate cancer, says Eric Li, MD.
Robust genetic testing guidelines in the prostate cancer space must be supported by strong clinical research before they can be properly implemented, says William J. Catalona, MD.
Financial constraints and a lack of education among some patients and providers must be addressed to improve the real-world use of certain prostate cancer therapies, says Neeraj Agarwal, MD.
Novel anti-PSMA monoclonal antibody rosopatamab is capable of carrying a bigger payload of radiation particles, which may potentially reduce doses for patients with prostate cancer, says Neeraj Agarwal, MD.
Findings from recent studies support the use of artificial intelligence-based tools in the context of radiation therapy for patients with localized prostate cancer, according to Neeraj Agarwal, MD.
Germline testing may elucidate important mutations in patients with metastatic prostate cancer who may be eligible to receive treatment with PARP inhibitors, according to Neeraj Agarwal, MD.
In this September edition of Snap Recap, we share our highlights from Prostate Cancer Awareness Month, news in the breast cancer space, and the latest FDA updates.
Artificial intelligence programs may help introduce new care strategies that minimize the risk of adverse effects in patients with prostate cancer, according to Wayne G. Brisbane, MD.
Related Content