Aggarwal R, Rydzewski NR, Zhang L, et al. - The findings constitute the biggest integrated clinical, transcriptomic, and genomic analysis of metastatic castration-resistant prostate cancer (mCRPC) samples to date, and they imply that mCRPC can be classified as luminal or basal tumors. Similar to primary prostate cancer, these findings imply that the benefit of androgen-signaling inhibitor (ASI) treatment is greater in luminal tumors and justify the use of ASIs in this population. Given the similarities to SCNC and the limited effectiveness of ASI therapy in basal tumors, some individuals may benefit from chemotherapeutic treatment.

• The luminal tumors were found in 288 (45%) of the 634 patients, while the basal tumors were found in 346 (55%).

• However, 53 of the 59 SCNC tumors were basal.

• Luminal tumors, like primary prostate cancer, had upregulation of AR pathway genes.

• Basal tumors had a much greater rate of RB1 loss, FOXA1 alterations and MYC alterations.

• Patients with basal tumors had worse overall survival vs those with luminal tumors only in patients treated with an ASI postbiopsy.

• Patients with luminal tumors who were treated with an ASI had a much better prognosis than those with basal tumors.

• There was a statistically significant interaction term between subtype and ASI treatment.