The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.
The objective of the present study is to assess the safety and feasibility of the use of telemedicine-based services for surgical wound care and to measure patient satisfaction with telemedicine-based follow-up. 24 patients were included, they were provided with a corporate mail address. On day 7 after surgery patients sent, via email, an image of their surgical wound together with a completed questionnaire in order to obtain an early diagnosis. Two independent physicians studied this information and the histologic analysis of the specimen. On day 8, all patients underwent face-to-face office examination by a third physician and all of them completed a satisfaction questionnaire at the end of the study. The use of telemedicine-based services showed a sensitivity of 100%, a specificity of 91.6%, a positive predictive value of 75% and a negative predictive value of 100%. Degree of concordance between the two physicians, as regards the necessity of face-to-face follow-up yielded a kappa coefficient of 0.42 (standard error 0.25 and confidence interval 95% (0.92-0.08), which means a moderate agreement between the two evaluations. 94% of patients were satisfied with telemedicine-based follow-up and 93% showed their preference for this procedure over conventional methods. The telemedicine-based follow-up, has proven to be feasible and safe for the evaluation of early postoperative complications. Patients reported high levels of satisfaction with the procedure. Telemedicine-based follow-up could become standard practice with the development of a specific mobile application.
PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.