The Future of Localized Prostate Cancer Treatment: Mary-Ellen Taplin, MD, and the PROTEUS Trial

At the 2026 American Society of Clinical Oncology Annual Meeting, Pharmacy Times spoke with Mary-Ellen Taplin, MD, a medical oncologist at Dana-Farber Cancer Institute and a leading investigator in the PROTEUS trial (NCT03767244), about the landmark phase 3 study evaluating perioperative apalutamide (Erleada; Janssen Products, LP) in high-risk localized prostate cancer, and what its results could mean for the future of curative-intent treatment.

Pharmacy Times: Prostate cancer in the localized, curative-intent setting isn’t where most medical oncologists plant their flag—it’s traditionally a urologist’s domain. What drew you to this specific moment in the disease, before metastasis, when there's still a chance to cure it?

Mary-Ellen Taplin, MD: Thank you for that question. Yes, typically localized prostate cancer is diagnosed and treated by urologists, but at Dana-Farber Cancer Institute, we have a very multidisciplinary approach to cancer, and medical oncologists are involved in most prostate cancer patients' journeys from the very beginning. Over the course of my practice, I was seeing a lot of patients with localized high-risk prostate cancer, and I really understood the concept of applying therapies early to prevent relapse and effect a cure. A higher cure rate is a very high target but very meaningful, and that’s what I chose to focus on for these patients. Across the board in oncology, we see therapies moving into earlier lines—myeloma, CAR [chimeric antigen receptor] T-cell therapy. How can we address cancer in its earliest stages? That thinking is very much at the heart of this work.

Pharmacy Times: When you started designing trials around perioperative intensification years ago, was this a widely accepted idea or were you pushing against conventional wisdom? What did that resistance—if there was any—look like?

Taplin: I would say we were pushing against conventional wisdom to some extent. The field, for decades, was doing surgery and sort of dealing with relapses later or telling patients they were too high risk to be a good surgical candidate and recommending hormones and radiation—hormone therapy with radiation for high-risk disease can be quite long, on average about 2 years. So we did a series of small phase 2 trials starting in 2009, with 50 to 120 patients, and kept exploring various hypotheses around androgen deprivation therapy intensification using androgen receptor pathway inhibitors. Each trial looked more and more positive.

As we built up the data and a patient database in Boston, we could retrospectively see that patients who had a major pathologic response weren’t relapsing—they had freedom from PSA failure and eventually freedom from metastasis. Those data over a 14-year period really provided the hypothesis and the pre–phase 3 groundwork for PROTEUS, and gave Janssen, now J&J, the courage to invest in a large phase 3 trial. What’s remarkable is that PROTEUS is the first phase 3 trial in localized high-risk prostate cancer in 13 years—a 13-year interval between the PUNCH trial and the start of PROTEUS. That’s a long gap for a group of patients with such a high relapse rate and such a clear unmet need.

Pharmacy Times: Without getting deep into the numbers, what was the moment during the trial when you felt something important was happening? Was there an interim look, a patient conversation, a signal that told you this was going to be meaningful?

Taplin: That’s a great question, but honestly, the trial was blinded. We had 77 patients at Dana-Farber out of 2109 total, and we had no idea which patients were receiving apalutamide and which were receiving placebo. The statistical plan had 3 planned analyses, and we ended up going all the way to the third and final one. We literally didn’t know the trial was positive until the results were unblinded, which happened just this past February. We prepared the ASCO Plenary presentation and the New England Journal [of Medicine] paper in a matter of weeks. It’s exciting—it truly is hot off the press.

Pharmacy Times: You’ve watched apalutamide move through the disease spectrum from nmCRPC to metastatic hormone-sensitive disease and now into the perioperative setting. What does it mean to you to see a drug you’ve worked with travel that far along the treatment continuum?

Taplin: What it means to me is that it’s good for patients. It’s affecting better outcomes across the spectrum—from our most advanced metastatic castration-resistant patients all the way up to those with localized but high-risk disease. The eligibility criteria for PROTEUS were stringent; these weren't simply high-risk patients in a general sense. If you had a Gleason 8 tumor in only 2 core biopsies, you couldn't enroll; you needed 6 core biopsies. Twelve percent had evidence of lymph node spread in the pelvis at entry, and we allowed that. I'm excited that an androgen receptor pathway inhibitor like apalutamide can potentially prevent roughly 20% of patients from relapsing and spare them the morbidity of subsequent therapy.

I can tell you as a clinician: seeing these patients come in every 3 months, getting a PSA of 0—it was like giving them a million dollars. They're very focused on that number. And having a therapy that extends remission for so long, with almost a 3-year difference in time to needing the next therapy for those who did need it, is just remarkable. It's also a limited, 1-year course of therapy: 82% of patients recovered their testosterone quickly, with a median recovery in the 7- to 8-month range. That's very meaningful for quality of life.

Pharmacy Times: If PROTEUS changes the standard of care, what's the version of this story you want told in 10 years? Not just about the drug, but about what it meant to treat prostate cancer differently at this moment in time.

Taplin: PROTEUS is just the beginning. The immediate story is that this will become a new standard-of-care option for patients with localized high-risk disease—they can weigh with their physicians the potential [adverse] effects of 3 components of therapy––androgen deprivation, surgery, and radiation––and choose the path that's right for them. But with the extensive biomarker work we're doing, hopefully the next set of trials will rationally design therapies, adding to androgen deprivation in appropriate patients, to achieve an even higher cure rate. And why PROTEUS is paradigm-changing is that with the power of 2109 patients, we should be able to prove that major pathologic response correlates with metastasis-free survival.

I envision a time when therapy development moves much more quickly. PROTEUS started in 2019; it's now 2026—that's 7 years and longer if you count protocol development. We only got there in that time because of the shift in standard of care around PSMA PET for staging. Looking back in 10 years, I hope PROTEUS will have changed the field on all of those fronts: more rational development of new therapies, faster development of new therapies, and ultimately a future where a patient walks in, gets their testing done, and receives recommendations based on clinical trials that bring the cure rate for these patients to 98%.