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  • Risk categories (low, intermediate, and high) for localized prostate cancer based on T-stage, grade grouping, and prostate-specific antigen at diagnosis help guide treatment approaches. Whereas men with low-risk prostate cancer should be considered for active surveillance, men with high-risk disease should be considered for definitive therapy after confirming no evidence of distant metastatic disease. Although favorable intermediate-risk disease can also be considered for active surveillance, definitive treatment of patients with unfavorable intermediate-risk disease is recommended if life expectancy is 10 years or longer and can be considered on a patient-by-patient basis depending on comorbid conditions.

  • For men with high-risk localized prostate cancer, multiple studies have confirmed the additive benefit of androgen-deprivation therapy (ADT) plus radiation over either modality alone. Furthermore, the addition of second-generation antiandrogens (eg, abiraterone acetate and prednisone) has been shown to improve disease-free survival over ADT alone when given with radiation therapy. The optimal duration of androgen ablative therapy in this setting is still under investigation.

  • ADT remains the backbone of treatment for men with recurrent prostate cancer. However, prolonged ADT has high potential morbidity, and recurrent prostate cancer is a heterogeneous disease. For nonmetastatic castrate-sensitive recurrence after definitive local therapy, intermittent ADT can be considered. For metastatic castrate-sensitive disease, intermittent ADT failed to show noninferiority to continuous ADT; however, with second-generation antiandrogens being moved into the metastatic castrate-sensitive space, the treatment decision should be made on a patient-by-patient basis.

  • Androgen biosynthesis inhibition as well as androgen receptor inhibitors have been moved earlier in the treatment of patients with prostate cancer with multiple approvals in the nonmetastatic castrate-resistant setting (darolutamide, apalutamide, enzalutamide) and the M1 castrate-sensitive setting (abiraterone acetate with prednisone, enzalutamide, and apalutamide). Choice of inhibitor should be based on side effect profile and the patient's comorbid conditions.

  • All men with metastatic prostate cancer, as well as those with high-risk localized prostate cancer, should be considered for germline genetic testing regardless of family history. This test should include analysis for variants in BRCA1/2, and other DNA damage response (DDR) genes should be considered for testing. Men with localized disease that is not high risk should be considered for genetic testing if there is a strong family history of hereditary prostate cancer or concern for hereditary breast and ovarian cancer syndrome. Men with deleterious variants in BRCA1/2 (somatic or germline) with prostate cancer who have progressed on standard-of-care second-generation antiandrogen(s) should be considered for treatment with poly (ADP-ribose) polymerase (PARP) inhibition (eg, olaparib [PROfound] or rucaparib [TRITON]). In addition, men with DDR gene alterations or hypermutated cancers (eg, high microsatellite instability or loss of mismatch repair protein expression) should be considered for immune checkpoint blockade because trials have shown these alterations can predict for response to immune checkpoint blockade (CheckMate 650).

  • AVPC (androgen-indifferent) and neuroendocrine prostate cancer are molecularly characterized by aberrations in TP53, RB1, and/or PTEN. These cancers have been shown to benefit from carboplatin-based chemotherapy (eg, carboplatin with cabazitaxel). Active research is ongoing to better define and ...

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