Navigating Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

When treating hormone-sensitive prostate cancer (mHSPC), one question can be, when is the right time to optimize or intensify therapy? In the latest Oncology Decoded podcast, genitourinary oncologists discuss the use of radiotherapy and define oligometastatic disease including preferred treatment options. The discussion took place during the 2025 ASCO Genitourinary Cancers Symposium.

The expert panel consisted of:

• Manojkumar Bupathi, MD, MS, executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute; medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers;
• Benjamin Garmezy, MD, associate director of Genitourinary Research and executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI); medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers;
• David Morris, MD, MS, president of Urology Associated, PC;
• Tanya Dorff, MD, professor in the Department of Medical Oncology & Therapeutics Research and section chief of the Genitourinary Disease Program at City of Hope;
• Mark T. Fleming, MD, medical oncologist at Virginia Oncology Associates; disease chair of the Genitourinary Cancer Research Executive Committee for SCRI at Virginia Oncology Associates.

The discussion centered around a challenging case of a 50-year-old male who had hematuria, penile pain, and a high prostate-specific antigen, with imaging revealing a Gleason 4+5 adenocarcinoma and metastatic lymph node involvement.

The panel agreed that androgen deprivation monotherapy was insufficient for this patient. The conversation quickly shifted to the optimal intensification strategy, with a focus on balancing efficacy and toxicity. Morris advocated for a combination of radiotherapy and androgen deprivation therapy (ADT) plus an androgen receptor signaling inhibitor, while acknowledging the patient didn’t strictly meet criteria for triplet therapy with chemotherapy. Dorf and Fleming favored doublet therapy with an androgen receptor pathway inhibitor and radiation, but also highlighted the importance of discussing chemotherapy, particularly given the patient’s young age and aggressive disease characteristics.

A key point of contention was the role of docetaxel. While some panelists acknowledged its potential benefit, concerns about toxicity and the lack of clear high-burden disease criteria in this case led to a general preference for radiation therapy for local debulking.

The discussion also explored the concept of oligometastatic disease, with the panel generally agreeing on a threshold of less than 5 metastatic sites. However, the location of these sites was deemed crucial, with lymph node and bone metastases considered more amenable to radiation therapy than visceral involvement. The importance of multidisciplinary input, including radiation oncology, was emphasized in determining the optimal treatment approach.

The use of imaging for surveillance was another key topic. While PSMA PET imaging was considered the gold standard for sensitivity and specificity, challenges with insurance coverage and the need for consistent imaging modalities were acknowledged. The panelists also highlighted the importance of considering de-differentiation and the potential for false positives with PSMA PET scans.

Ultimately, the discussion underscored the importance of individualized treatment decisions in mHSPC, considering patient age, disease burden, risk factors, and preferences. The panel emphasized the need for ongoing research to refine treatment strategies and improve outcomes for patients with this complex disease.

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