Search

Simple Summary: Multiple randomized trials have highlighted the importance of combining Androgen Deprivation Therapy (ADT) and Radiotherapy in the management of localized intermediate (IR) and high-risk (HR) prostate cancer (PCa). Recent trials have shown that the moment of initiation of ADT seems to be clinically relevant. The purpose of our review was to compile the available evidence on behalf of the combination of RT and ADT, focusing on the sequencing of both modalities to provide recommendations on the optimal timing to start the hormonal therapy. Background: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. Methods: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. Findings: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. Interpretation: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent practice-changing trials have highlighted the importance of polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) in metastatic castrate resistant prostate cancer (mCRPC). PARP plays a quintessential role in repairing deoxyribonucleic acid (DNA) single-strand breaks by signaling and recruiting the necessary repair machinery to damaged areas. In mCRPC, where mutations are more likely to impair important repair pathways such as the homologous recombinational repair (HRR), remaining PARP repair pathways become critical to cell survival and can be exploited with targeted therapies. The purpose of our review was to compare and contrast recent pivotal trials in this setting and explore future avenues of research. Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer. [ABSTRACT FROM AUTHOR]