Clinical Implications of Luminal and Basal Subtyping of Prostate Cancer

Key Points

  • Outcomes were poorer for luminal B vs luminal A and basal cancers.
  • Only luminal B disease was associated with an improved outcome with postoperative androgen-deprivation therapy.

As reported by Zhao et al in JAMA Oncology, luminal B prostate cancers carry a worse overall prognosis than luminal A and basal-like cancers, but luminal B tumors respond better to postoperative androgen-deprivation therapy.

Study Details

In the study, the PAM50 classifier was used to subtype 1,567 retrospectively collected (median follow-up = 10 years) and 2,215 prospectively collected (clinical outcomes not available) formalin-fixed, paraffin-embedded radical prostatectomy samples into luminal- and basal-like subtypes. Retrospective cohorts were from The Mayo Clinic, Cleveland Clinic, Johns Hopkins University, Thomas Jefferson University, and Durham Veterans Affairs (North Carolina); prospective samples were from the Decipher GRID study.

Distribution of Subtypes

Among the 3,782 samples, the PAM50 classifier consistently segregated tumors into three subtypes in both the retrospective and prospective cohorts: luminal A (34.3% and 33.3%), luminal B (28.5% and 32.6%), and basal (37.1% and 34.1%). Luminal-like cancers were enriched for such luminal lineage markers as NKX3.1 and KRT18, and basal-like cancers were enriched for the basal lineage CD49f signature.

Prognoses

The 10-year actuarial rates were poorer for luminal B cancers vs luminal A and basal cancers for biochemical recurrence–free survival (29% vs 41% and 39%), distant metastasis–free survival (53% vs 73% and 73%), prostate cancer–specific survival (78% vs 89% and 86%), and overall survival (69% vs 82% and 80%). On multivariable analysis adjusting for clinicopathologic variables, outcomes for basal and luminal A tumors were significantly better vs luminal B tumors for biochemical recurrence–free survival (hazard ratio [HR] = 0.81, P = .01; HR = 0.79, P = .005) and distant metastasis–free survival (HR = 0.66, P < .001; HR = 0.55, P < .001); luminal A tumors had significantly better outcomes vs luminal B tumors for prostate cancer–specific survival (HR = 0.50, P < .001) and overall survival (HR = 0.69, P = .002).

Response to Androgen-Deprivation Therapy

Both luminal-like subtypes were associated with increased androgen receptor expression and signaling. However, in a subset analysis of 315 patients matched for clinicopathologic variables, only luminal B tumors were significantly associated with a postoperative response to androgen-deprivation therapy. For patients receiving vs not receiving androgen-deprivation therapy, 10-year metastasis rates were 33% vs 55% in patients with luminal B disease compared with 37% vs 21% in those with non–luminal B disease (P = .006 for interaction). Outcomes were similar in the luminal A and basal groups.

The investigators concluded: “Luminal- and basal-like prostate cancers demonstrate divergent clinical behavior, and patients with luminal B tumors respond better to postoperative [androgen-deprivation therapy] than do patients with non–luminal B tumors. These findings contribute novel insight into prostate cancer biology, providing a potential clinical tool to personalize [androgen-deprivation therapy] treatment for prostate cancer by predicting which men may benefit from [androgen-deprivation therapy] after surgery.”

The study was funded by the Prostate Cancer Foundation, Evans Foundation, V Foundation for Cancer Research, and Alfred Taubman Medical Research Institute.

Felix Y. Feng, MD, of Helen Diller Comprehensive Cancer Center, University of California, San Francisco, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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