Acta Clinica Croatica (Jan 2024)
A New Paradigm in the Systemic Treatment of Advanced Prostate Cancer: the Earlier the Better or the More the Better
Abstract
Androgen deprivation therapy (ADT) has been the backbone of treatment for advanced prostate cancer (APC) for decades. The introduction of docetaxel and androgen receptor pathway inhibitors (ARPI; abiraterone, enzalutamide, apalutamide) in the treatment of metastatic hormone- sensitive PC (mHSPC) has changed the treatment landscape of APC. Data from studies with docetaxel (CHAARTED, STAMPEDE) and NHT (STAMPEDE, LATITUDE, ENZAMET, ARCHES, TITAN) suggest that ADT monotherapy is no longer acceptable for the treatment of men with mHSPC. Systemic treatment options in this indication include: doublet therapy consisting of ADT plus abiraterone (AAP) or apalutamide (APA), or enzalutamide (ENZ); ADT plus docetaxel remains an option for settings where ARPI is not available or the combination of ADT and docetaxel with ARPI is not possible, and triple therapy consisting of a combination of ADT, docetaxel, and AAP or darolutamide (PEACE-1, ARASENS studies), especially for patients with high-risk/high-volume synchronous disease. More data are needed on the potential combination of ADT with docetaxel and APA or ENZ. In the decision to treat a patient with mHSPC, in addition to the results of relevant studies, the general condition of the patient, their comorbidities and co-medication, affinities, availability and toxicity of drugs, and the cost of treatment should all be taken into account. Finally, further elucidation of the biology of different groups of mHSPC to identify different clinical behavior may be helpful in deciding the optimal treatment of these patients. Analysis of transcriptomic biomarkers of patient samples from large, practice-changing mHSPC studies could optimize patient selection for different treatment strategies and help physicians make decisions in daily practice.
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