Prostate Cancer

PSA-based screening can detect clinically significant prostate cancer but also produces false-positive results, overdiagnosis, anxiety, and treatment-related harms. The AUA/SUO early-detection guideline emphasizes PSA-based screening with increasing use of biomarkers and multiparametric MRI to identify clinically significant cancer while reducing unnecessary biopsy and detection of low-risk disease. auajournalsauajournalsAUA/SUO Guideline Part I: Prostate Cancer Screening

No single PSA threshold reliably distinguishes cancer from benign disease. Screening trials used biopsy thresholds ranging from 2.5 to 10.0 ng/mL, and historic data indicate that a 3 ng/mL threshold can miss clinically significant cancers. PSA should therefore be treated as a continuous risk estimate integrated with examination findings, prior PSA values, patient risk factors, and patient preferences. JAMA+3JAMAPopulation-Based Prostate Cancer Screening With ...JAMAUSPSTF Recommendation: Screening for Prostate CancerJAMAPSA Thresholds for Prostate Cancer Detection-ReplyNEJMEffect of Verification Bias on Screening for Prostate Cancer ...

Men considering screening should understand that the purpose is earlier detection of potentially consequential cancer, not diagnosis by PSA alone. The 2018 USPSTF evidence review documents heterogeneous screening intervals, ranging from one-time screening to every 1 to 4 years, and heterogeneous PSA thresholds across trials; these differences contribute to variable screening outcomes and preclude a universal operational threshold. JAMAJAMAUSPSTF Recommendation: Screening for Prostate Cancer

MRI may help detect prostate cancer, but it does not replace pathologic diagnosis when cancer suspicion remains sufficient to warrant tissue sampling. Biopsy determines cancer presence and provides histologic assessment of aggressiveness, reported using Gleason score. fdafdaProstate Cancer Symptoms, Tests and Treatments | FDA

After diagnosis, treatment planning depends on the likelihood of disease outside the prostate. FDA notes that additional imaging may be required when the risk of spread is high. This staging step determines whether a local-only approach is adequate or whether systemic therapy, radiation-field expansion, or multidisciplinary evaluation is needed. fdafdaProstate Cancer Symptoms, Tests and Treatments | FDA

Clinical documentation should preserve the disease state at each transition: localized disease, post-local-therapy biochemical recurrence, metastatic castration-sensitive disease, or metastatic castration-resistant disease. These states carry different regulatory indications and systemic treatment options. accessdata fda+3accessdata fdaReference ID: 5607383 - accessdata.fda.govfdaFDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence | FDAfdaFDA approves darolutamide for metastatic castration-sensitive prostate cancer | FDAfdaFDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication | FDA

Localized prostate cancer management remains controversial because many tumors have an indolent course whereas a subset can progress. In a 15-year trial comparing monitoring, surgery, and radiotherapy for localized prostate cancer, these approaches remained central management strategies, underscoring the need for individualized selection rather than a single default intervention. NEJMNEJMFifteen-Year Outcomes after Monitoring, Surgery, or ...

FDA identifies radiation therapy and/or surgery as preferred treatment for localized prostate cancer at risk for spread. Radiation may also be administered after surgery in selected patients at high risk of residual prostate cancer. The expected tradeoffs include urinary effects, erectile dysfunction, and bowel problems after surgery or radiation. fdafdaProstate Cancer Symptoms, Tests and Treatments | FDA

Surveillance or monitoring is particularly relevant when the expected natural history is favorable and treatment morbidity is likely to outweigh near-term benefit. A review of prognosis notes that men with well-differentiated disease can often survive 10 to 20 years without intervention, whereas poorly differentiated disease has a less favorable course. This is supportive prognostic context rather than a substitute for contemporary risk stratification. Oxford AcademicOxford AcademicWhat Is the Risk Posed by Prostate Cancer? - Oxford Academic

In November 2023, the FDA approved enzalutamide for patients with high-risk nonmetastatic castration-sensitive prostate cancer with biochemical recurrence. Enzalutamide may be administered with or without a gonadotropin-releasing hormone analog. fdafdaFDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence | FDA

The FDA-recommended enzalutamide dose in this setting is 160 mg orally once daily with or without food until disease progression or unacceptable toxicity. Treatment may be suspended when PSA becomes undetectable, defined as less than 0.2 ng/mL, after 36 weeks; treatment may be restarted when PSA reaches at least 2.0 ng/mL after radical prostatectomy or at least 5.0 ng/mL after primary radiation therapy. fdafdaFDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence | FDA

Reported common adverse reactions differ by use with leuprolide versus monotherapy. With enzalutamide plus leuprolide, common events include hot flush, musculoskeletal pain, fatigue, falls, and hemorrhage; with monotherapy, common events include fatigue, gynecomastia, musculoskeletal pain, breast tenderness, hot flush, and hemorrhage. fdafdaFDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence | FDA

ADT suppresses testosterone production or blocks androgen action on prostate cancer cells. FDA describes ADT as standard care for metastatic prostate cancer and notes that radiation therapy is sometimes combined with hormone therapy. Loss of testosterone drives many ADT toxicities. fdafdaProstate Cancer Symptoms, Tests and Treatments | FDA

Darolutamide received FDA approval in June 2025 for metastatic castration-sensitive prostate cancer. In the ARANOTE trial, all participants also received a gonadotropin-releasing hormone analog or had prior bilateral orchiectomy, reinforcing that darolutamide is used in the context of maintained castration. fdafdaFDA approves darolutamide for metastatic castration-sensitive prostate cancer | FDA

The recommended darolutamide dose is 600 mg orally twice daily with food until disease progression or unacceptable toxicity. The prescribing information includes warnings and precautions for ischemic heart disease, seizure, and embryo-fetal toxicity. fdafdaFDA approves darolutamide for metastatic castration-sensitive prostate cancer | FDA

Talazoparib is FDA labeled in combination with enzalutamide for adults with homologous recombination repair gene-mutated mCRPC. The recommended talazoparib dose is 0.5 mg orally once daily with enzalutamide until disease progression or unacceptable toxicity; patients should also receive a GnRH analog or have undergone bilateral orchiectomy. Moderate or severe renal impairment requires dose reduction and increased monitoring for adverse reactions. accessdata fdaaccessdata fdaReference ID: 5607383 - accessdata.fda.gov

In March 2025, the FDA expanded the indication for lutetium Lu 177 vipivotide tetraxetan to adults with PSMA-positive mCRPC previously treated with an androgen receptor pathway inhibitor and considered appropriate to delay taxane-based chemotherapy. Patients should be selected with gallium Ga 68 gozetotide or another approved PSMA PET agent on the basis of tumor PSMA expression. fdafdaFDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication | FDA

The FDA-recommended lutetium Lu 177 vipivotide tetraxetan regimen is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to six doses, or until progression or unacceptable toxicity. Important risks include radiation exposure, myelosuppression, and renal toxicity. fdafdaFDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication | FDA

Docetaxel remains an FDA-labeled treatment in metastatic castration-resistant prostate cancer. The supplied label specifies administration only when the neutrophil count is at least 1,500 cells/mm3 and recommends dose reduction from 75 mg/m2 to 60 mg/m2 after febrile neutropenia, prolonged severe neutropenia, severe or cumulative cutaneous reactions, or moderate neurosensory symptoms; persistent toxicity may require reduction to 45 mg/m2. accessdata fdaaccessdata fdadocetaxel injection - accessdata.fda.gov

The highest-value recurring task is to define the current disease state accurately and then align testing with an actionable treatment decision. MRI, biopsy, staging imaging, germline or tumor-directed testing where indicated, and PSMA PET each have different purposes; none should be ordered reflexively without a planned consequence for the result. fda+3fdaProstate Cancer Symptoms, Tests and Treatments | FDAaccessdata fdaReference ID: 5607383 - accessdata.fda.govfdaFDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication | FDAauajournalsAUA/SUO Guideline Part I: Prostate Cancer Screening

Treatment-related morbidity must be managed as part of cancer care. Surgery and radiation can affect urinary, sexual, and bowel function; ADT causes effects largely attributable to testosterone loss; darolutamide carries ischemic heart disease and seizure warnings; radioligand therapy can cause myelosuppression and renal toxicity; and docetaxel requires hematologic and toxicity-directed dose modification. fda+3fdaProstate Cancer Symptoms, Tests and Treatments | FDAaccessdata fdadocetaxel injection - accessdata.fda.govfdaFDA approves darolutamide for metastatic castration-sensitive prostate cancer | FDAfdaFDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication | FDA

Multidisciplinary discussion is particularly useful when there is uncertainty about local treatment candidacy, postoperative radiation, high-risk biochemical recurrence, molecularly selected mCRPC therapy, or sequencing of radioligand therapy versus taxane chemotherapy. The available sources establish relevant therapies and regulatory criteria but do not provide a complete contemporary sequencing algorithm. fda+3fdaProstate Cancer Symptoms, Tests and Treatments | FDAaccessdata fdaReference ID: 5607383 - accessdata.fda.govfdaFDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence | FDAfdaFDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication | FDA