Among patients with metastatic castration-resistant prostate cancer (mCRPC), androgen signaling inhibitors (ASIs) may be more beneficial for patients with luminal tumors than for those with basal tumors, according to research published in JAMA Oncology.
Researchers conducted a clinical, transcriptomic, and genomic analysis of samples from 4 cohorts of patients with mCRPC. The primary clinical endpoint was overall survival (OS) from the date of tissue biopsy or molecular profiling.
Of the 634 patients analyzed, 45% had luminal tumors, and 55% had basal tumors. The vast majority (90%) of small cell/neuroendocrine prostate cancers (SCNCs) were basal (P <.001).
“Small cell/neuroendocrine prostate cancer is thought to be androgen independent, and thus one would expect it to be more similar to basal tumors compared with luminal tumors,” the researchers wrote. “[T]he data presented in this report suggest that the luminal-ness and basal-ness of metastatic prostate tumors lies on a spectrum, and that SCNC tumors largely represent the most basal-like in nature along this continuum.”
The researchers also found that luminal tumors were characterized by overexpression of androgen receptor pathway genes. Basal tumors, on the other hand, had higher rates of RB1 loss (P <.001), FOXA1 alterations (P =.03), and MYC alterations (P <.001).
Patients with luminal tumors had significantly longer OS if they were treated with ASIs. The median OS was 32.0 months in patients who received ASIs and 8.7 months in those who did not (hazard ratio [HR], 0.27; 95% CI, 0.14-0.53; P <.001).
For patients with basal tumors, there was no significant OS benefit with ASIs (HR, 0.62; 95% CI, 0.36-1.04; P =.07).
“In the basal tumors, a chemotherapeutic approach could be considered in some patients given the similarity to SCNC and the diminished benefit of ASI therapy,” the researchers wrote.
They added, however, that these findings should be validated in prospective clinical trials.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Aggarwal R, Rydzewski NR, Zhang L, et al. Prognosis associated with luminal and basal subtypes of metastatic prostate cancer. JAMA Oncol. Published online September 23, 2021. doi:10.1001/jamaoncol.2021.3987