Dr. Karim Fizazi, a renowned oncologist and prostate cancer expert at Gustave Roussy Cancer Center in France, is challenging traditional approaches to treating metastatic hormone-sensitive prostate cancer (mHSPC). His perspectives push the field beyond the simple classification of metastases by volume, advocating for a more nuanced view that considers the timing and biology of the disease.

Historically, mHSPC treatment has been guided by the CHAARTED trial, which classified patients into low-volume or high-volume disease based on the number of bone metastases. Treatment decisions were largely influenced by this classification, with low-volume disease often treated with ADT (androgen deprivation therapy) and an androgen receptor (AR) pathway inhibitor, while high-volume disease typically involved triplet therapy (ADT, docetaxel, and an AR inhibitor).

Dr. Fizazi argues that this approach oversimplifies the complexity of mHSPC. Instead, he emphasizes the importance of the timing of metastasis:

• Relapsed/metachronous disease (metastases occurring after initial local treatment) generally indicates a better prognosis, with patients often living at least eight years after diagnosis. These patients typically do not benefit from docetaxel chemotherapy.
• De novo/synchronous disease (metastases present at the time of initial diagnosis), on the other hand, tends to be more aggressive. Even patients with low-volume de novo disease show significant benefit from docetaxel, underscoring the need for triplet therapy in these cases, especially in younger and fitter patients.

A recent meta-analysis confirms Dr. Fizazi’s view: while docetaxel provides no survival benefit for relapsed low-volume disease, it significantly improves outcomes in de novo disease, regardless of metastatic volume. This finding challenges the traditional notion of withholding docetaxel for low-volume cases, advocating for its use based on disease timing rather than volume alone.

Radiation therapy also plays a nuanced role. Results from the PEACE-1 trial suggest that while radiation to the primary tumor does not improve overall survival (OS) in de novo mHSPC, it effectively prevents local symptoms such as bleeding, obstruction, and pain. Radiation should therefore be considered for both low- and high-volume de novo disease to enhance quality of life, especially when combined with abiraterone, which may offer a synergistic effect.

Dr. Fizazi highlights the importance of biomarkers in shaping the future of mHSPC treatment. Biomarkers like BRCA1, BRCA2, and PTEN could help refine treatment strategies, while PSMA PET imaging holds promise as a predictive tool.

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