[VIDEO & SLIDES] Alex Chehrazi –Raffle, MD, City of Hope – 2024 MOASC Annual Oncology Summit & Research Symposium
In the ever-evolving field of oncology, the management of non-metastatic prostate cancer represents a significant area of interest due to the potential for curative treatment outcomes. With advancements in diagnostic techniques and treatment modalities, the approach to treating non-metastatic prostate cancer is becoming increasingly sophisticated. This article builds upon the insights provided by Alex Chehrazi-Raffle, MD, from the City of Hope Comprehensive Cancer Center, to explore the nuanced strategies in the systemic treatment of non-metastatic prostate cancer. It covers the established treatment paradigms, recent updates in management, especially for M0 castration-resistant prostate cancer (CRPC) with a prostate-specific antigen doubling time (PSADT) of less than 10 months, and outlines future directions for this field.
Updated Management Strategies for Non-Metastatic CRPC
One of the most significant updates in the management of non-metastatic CRPC has been the adoption of androgen receptor pathway inhibitors (ARPIs) for patients with a PSADT of less than 10 months. This group of patients, previously faced with limited systemic treatment options until the development of metastases, now benefits from earlier intervention with ARPIs, which has been shown to substantially delay the progression to metastatic disease. Recent trials, such as those cited by Fizazi et al., Hussain et al., and Smith et al. in the New England Journal of Medicine in 2018 and 2019, have demonstrated the efficacy of ARPIs, including enzalutamide, apalutamide, and darolutamide, in extending metastasis-free survival in this patient population.
The DEAR study, as presented by George D et al. at ASCO 2023, further evaluates the real-world outcomes of these ARPIs, highlighting the fewer discontinuations or progression to metastasis among patients treated with darolutamide, underscoring the importance of selecting the appropriate ARPI based on patient-specific factors and tolerance profiles.
Traditional and Emerging Treatment Paradigms
The traditional treatment paradigm for non-metastatic prostate cancer has primarily focused on local therapies, such as surgery and radiation, with the addition of ADT in certain high-risk or locally advanced cases. However, the definition of biochemical recurrence (BCR) post-definitive therapy has refined the understanding and management strategies of non-metastatic prostate cancer. The criteria set by RTOG-ASTRO and researchers such as Kupelian et al. and Freedland SJ et al. offer a framework for identifying patients who may benefit from further treatment, such as salvage radiation therapy (xRT) with or without ADT.
Recent studies, including those by Pollack A et al., Carrie C et al., and Parker C et al., have investigated the benefits of adding short-term or long-term ADT to salvage xRT, showing varied impacts on patient outcomes. The nuanced decision-making process in whether to introduce ADT, and for how long, underscores the need for personalized treatment plans based on patient-specific factors such as tumor characteristics, PSA levels, and PSADT.
Navigating Treatment Selection and Future Directions
The PRESTO trial, referenced by Aggarwal et al. in the Journal of Clinical Oncology in 2024, and the EMBARK trial findings presented by Freedland et al. in the New England Journal of Medicine in 2023, offer invaluable insights into optimizing treatment for patients with high-risk BCR. These studies explore the efficacy of combining ARPIs with ADT, comparing dual therapy against ADT alone, and elucidating the potential benefits and drawbacks of incorporating these advanced hormonal therapies earlier in the treatment course.
Furthermore, the role of PSMA PET/CT in improving the detection of early metastatic disease and informing treatment decisions highlights the integration of advanced imaging technologies into the management of non-metastatic prostate cancer. The ongoing ARASTEP trial, as mentioned by Chehrazi-Raffle et al. at ASCO GU 2024, promises to shed light on the utility of PSMA PET/CT scans in tailoring treatment approaches for patients with non-metastatic prostate cancer.
3-Year Metastasis-Free Survival Rates from the EMBARK Trial. It compares the outcomes across three treatment groups: Enzalutamide + Leuprolide, Leuprolide Alone, and Enzalutamide Monotherapy.
Conclusion
The landscape of non-metastatic prostate cancer treatment is rapidly advancing, with significant strides made in refining treatment paradigms and integrating novel therapeutic agents. The implementation of ARPIs in the management of M0 CRPC with rapid PSADT has marked a pivotal shift towards more aggressive early intervention strategies, offering the potential to delay disease progression and improve patient outcomes. As the field continues to evolve, ongoing research and clinical trials will further delineate the most effective treatment combinations and sequences, ultimately guiding oncologists in providing personalized, evidence-based care to their patients. The future direction of non-metastatic prostate cancer management will likely continue to focus on the integration of molecular diagnostics, targeted therapies, and patient-specific treatment plans to optimize outcomes and quality of life for affected individuals.
Reference Links:
Anticancer Effect of Second-line Treatment for Castration-Resistant Prostate Cancer Following First-line Treatment with Androgen Receptor Pathway Inhibitors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8827108/
An Observational Study, Called DEAR, to Learn More About Treatment With Darolutamide, Enzalutamide and Apalutamide in Men With Non-metastatic Castration-resistant Prostate Cancer in Real World Settings (DEAR): https://clinicaltrials.gov/study/NCT05362149
OncologyTube Links:
Alicia K. Morgans, MD: https://oncologytube.com/alicia-k-morgans-md-capsurvivorship-danafarber-danafarber_gu-ascogu22-gu22-prostatecancer-identifying-profiles-mapping-pts-journey/