Herchenhorn, Daniel

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide evidence-based recommendations for patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS An Expert Panel including patient representation completed a systematic review of the evidence and made recommendations. RESULTS Depending upon prior treatment received, androgen receptor pathway inhibitors (ARPIs: enzalutamide, abiraterone with prednisone), poly(ADP-ribose) polymerase inhibitors (PARPi), chemotherapeutic agents (docetaxel, cabazitaxel), radiopharmaceuticals (radium 223, 177 Lu-prostate-specific membrane antigen [PSMA]-617), and sipuleucel-T have demonstrated an overall survival (OS) benefit for patients with mCRPC. For patients with BRCA1 / 2 alterations who did not receive prior ARPI, the combination of PARPi and ARPI (talazoparib + enzalutamide, olaparib and/or niraparib + abiraterone) has shown clinical benefit. For patients with BRCA1 / 2 alterations who received prior ARPI or ARPI followed by docetaxel, olaparib showed OS benefit. In select patients with microsatellite instability-high/mismatch repair-deficient, pembrolizumab showed clinical efficacy. RECOMMENDATIONS Prior systemic therapy for castration-sensitive prostate cancer will determine subsequent therapy used for mCRPC. Continue androgen-deprivation therapy for patients with mCRPC indefinitely. Early adoption of somatic genetic testing and palliative care is recommended. Patients with mCRPC and bony metastases should receive a bone-protective agent. The panel recommends the combination of ARPI with PARPi in patients with BRCA1 / 2 alterations who did not receive prior ARPI. For patients who received prior ARPI, the panel recommends docetaxel chemotherapy. The panel recommends 177 Lu-PSMA-617 or cabazitaxel chemotherapy for patients who receive prior ARPI and docetaxel chemotherapy. For patients with BRCA1 / 2 alterations who received prior ARPI, the panel recommends PARPi monotherapy. Radium 223 is recommended for patients with symptomatic bone–only disease. Evidence for optimal sequencing for mCRPC regimens is lacking. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .

PURPOSE To present a summary of the recommendations for the treatment and follow-up for the biochemical recurrence of castration-resistant prostate cancer (PCa) as acquired through a questionnaire administered at the Prostate Cancer Consensus Conference for Developing Countries. METHODS A total of 27 questions were identified as relating to this topic. Responses from the clinician were tallied and are presented in percentage format. Topics included the use of imaging in staging, treatment recommendations across different patient scenarios of life expectancy and prostate-specific antigen (PSA) doubling time, and follow-up for nonmetastatic castration-resistant PCa. RESULTS A consensus agreed that in optimal conditions, positron emission tomography-computed tomography with prostate-specific membrane antigen would be used although in limited resource situations the combined use of CT of the abdomen and pelvic (or pelvic MRI), a bone scan, and a CT of the thorax or chest x-ray was recommended. In cases when PSA levels double in < 10 months, more than 90% of clinicians agreed on the use of apalutamide or enzalutamide, regardless of life expectancy. With a doubling time of more than 10 months, > 54% of experts recommended no treatment independent of life expectancy. More than half of the experts, regardless of resources, recommended follow-up with a physical examination and PSA levels every 3-6 months and imaging only in the case of symptoms. CONCLUSION The voting results and recommendations presented in this document can be used by physicians to support management for biochemical recurrence of castration-resistant PCa in areas of limited resources. Individual clinical decision making should be supported by available data.