Metastasis-directed therapy (MDT), particularly through stereotactic body radiotherapy (SBRT), is reshaping the treatment landscape for metastatic prostate cancer. Traditionally, lifelong androgen deprivation therapy (ADT) has been the mainstay of treatment, but it often comes with significant side effects. Recent clinical trials have explored the efficacy of MDT in various contexts, offering insights into its potential benefits.

The STOMP trial investigated the use of MDT to delay the initiation of ADT in patients with oligometastatic hormone-sensitive prostate cancer (HSPC). Results indicated that MDT could postpone the need for ADT, providing patients with a reprieve from its associated side effects. Similarly, the ORIOLE trial demonstrated that SBRT for oligometastatic prostate cancer significantly improved progression-free survival compared to observation alone. Notably, long-term follow-up revealed that up to 20% of patients remained progression-free four years after MDT.

Combining MDT with short-term ADT has also been explored. The EXTEND trial found that adding MDT to intermittent hormone therapy for oligometastatic prostate cancer improved outcomes, suggesting that this combination could extend periods of normal testosterone levels while maintaining disease control.

In cases of oligoprogressive castration-resistant prostate cancer, the ARTO trial assessed the addition of MDT to a new line of systemic therapy. The study reported increased biochemical response rates and improved progression-free survival, indicating that MDT can effectively delay the need for further systemic treatments.

For patients with de novo low-volume HSPC, the PROLONG study evaluated a comprehensive treatment approach combining ADT, androgen receptor pathway inhibitors (ARPI), and SBRT to both the prostate and oligometastatic lesions. This regimen resulted in improved survival rates, particularly among patients with a low metastatic burden.

Even in advanced cases with extensive metastatic disease, MDT has shown promise. The ARREST study demonstrated that SBRT-MDT is a safe and feasible option for patients with polymetastatic disease, delivering targeted treatment to multiple lesions with minimal acute toxicity.

These findings underscore the potential of MDT, especially SBRT, to personalize treatment strategies for metastatic prostate cancer. By tailoring therapy to individual patient profiles, MDT offers avenues for both intensifying treatment in aggressive cases and de-escalating therapy to minimize side effects, ultimately enhancing patient quality of life. Ongoing large-scale trials are essential to further validate these approaches, optimize treatment durations, and identify biomarkers that can guide patient selection for MDT.

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