Leading Oncologists Say Prostate Cancer Treatment Is Shifting Beyond a One-Size-Fits-All Approach Toward More Personalized Care

“Prostate cancer is not a single disease,” Dr. Bilusic tells SurvivorNet, pointing to two experimental drugs he’s watching closely for patients with metastatic, hormone-resistant prostate cancer, which means the cancer has spread and stopped responding to standard hormone-blocking treatment.

Mevrometostat (PF-06821497) is an investigational EZH2 inhibitor. EZH2 is a protein that cancer cells can use to “reprogram” themselves and dodge hormone therapy. Blocking it is designed to make existing treatments, like enzalutamide (brand name Xtandi), work again.

In an early phase 1 study, adding mevrometostat to enzalutamide more than doubled the time before cancer progressed on scans: a median of 14.3 months, compared with 6.2 months on enzalutamide alone, a reduction of about 49% in the risk of disease progression or death.

Two large phase 3 trials — MEVPRO-1 and MEVPRO-2 — are now testing whether that early signal holds up in larger patient groups, with MEVPRO-1 open-label and MEVPRO-2 double-blind, evaluating mevrometostat plus enzalutamide against standard treatment.

Dr. Bilusic said he expects phase 3 results by the end of 2026.

WATCH: New Study Shows Potential for Earlier Use of Pluvicto in Advanced Prostate Cancer

Opevesostat works differently. It blocks an enzyme called CYP11A1, which sits at the very first step of the body’s hormone-production pathway.

By inhibiting CYP11A1, opevesostat can suppress the production of all steroid hormones and precursors that may activate androgen receptor signaling — which matters most for tumors that have developed a specific mutation (in the androgen receptor’s “ligand-binding domain”) that lets them keep growing despite hormone therapy.

Opevesostat is being tested in two ongoing, randomized phase 3 trials called OMAHA-003 and OMAHA-004.

Dr. Bilusic also flagged three other categories of drugs in development: T-cell engagers (which recruit a patient’s own immune cells to attack the tumor), androgen receptor degraders (which destroy the androgen receptor protein rather than just blocking it), and antibody-drug conjugates targeting proteins called STEAP1 and KLK2.

Dr. Noah Richardson, of Indiana University’s Melvin and Bren Simon Comprehensive Cancer Center, sees the same shift playing out in the treatment pipeline.

“Initial results have been promising in early trials and some larger trials are expected to have initial results in the near future,” Dr. Richardson said.

“We may see the results of T-cell engager immunotherapy drugs and new radioligand therapies in advanced castration-resistant prostate cancer soon. These could change how we sequence approved prostate cancer therapies and give more options to patients in deciding with oncologists what the best treatments are for them,” Dr. Richardson continued.

Approvals Expected Soon

Two more approvals are on Dr. Bilusic’s radar for the near term.

Talazoparib plus enzalutamide, for a broader use than it currently has. This PARP inhibitor combination is already approved for later-stage disease; Dr. Bilusic expects it to be approved for earlier-stage metastatic hormone-sensitive prostate cancer in patients whose tumors carry HRR gene alterations (a category of DNA-repair gene mutations that includes, but isn’t limited to, BRCA).

The FDA has accepted a supplemental new drug application for priority review for Talazoparib plus enzalutamide, with a decision date set for the fourth quarter of 2026.

Approval of talazoparib plus enzalutamide rests on the phase 3 TALAPRO-3 trial, which found that adding talazoparib to enzalutamide reduced the risk of radiographic progression or death by 52%, with consistent benefit across patients with BRCA and non-BRCA HRR gene alterations.

WATCH: Why Do PTEN Mutations Matter In Prostate Cancer?

Perioperative apalutamide — meaning apalutamide given both before and after surgery — for patients with high-risk localized or locally advanced prostate cancer undergoing prostate removal.

Dr. Bilusic believes a decision on this treatment is also on the horizon. This is based on the PROTEUS trial: apalutamide plus hormone therapy reduced the risk of metastasis or death by 20% compared with placebo plus hormone therapy.

A Very Active Summer

• June 12, 2026: The FDA approved capivasertib in combination with abiraterone and prednisone for patients with metastatic hormone-sensitive prostate cancer whose tumors lack a protein called PTEN — PTEN-deficient disease, detected using a newly approved companion diagnostic test.
• July 31, 2026: The FDA approved Pluvicto (a radioactive drug that targets a protein called PSMA on prostate cancer cells) in combination with a hormone-blocking drug, for patients with PSMA-positive metastatic hormone-sensitive prostate cancer — expanding its use from later-stage disease into this earlier setting.

What This Means For Newly Diagnosed Patients

Within a short window, Dr. Bilusic said, doctors have gained three separate ways to intensify treatment based on a tumor’s specific biology: PTEN-deficient disease (treated with capivasertib), PSMA-positive disease (treated with Pluvicto), and HRR-altered disease (treated with PARP inhibitor combinations).

The old approach — hormone therapy plus one additional pill for every patient — is, in his view, no longer good enough on its own.

Dr. Bilusic said everyone newly diagnosed with metastatic prostate cancer should now get a comprehensive workup that includes a PSMA PET scan, genetic testing (both inherited and tumor-specific) for HRR gene alterations, and PTEN testing on the tumor tissue.

Because a single patient may qualify for more than one biomarker-driven treatment strategy, and there are no head-to-head data comparing them directly, Dr. Bilusic said more research is needed to determine which approach—or combination—is best for which patient.

 

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