Prostate Cancer

Most prostate cancers are adenocarcinomas, but their behavior varies widely. Some remain slow-growing for years, whereas others invade locally, recur, or metastasize. A prostate-specific antigen (PSA) value alone cannot establish a diagnosis or determine treatment.

Evaluation integrates repeat PSA testing when appropriate, digital rectal examination, MRI, biopsy, Gleason score/Grade Group, stage, life expectancy, other health conditions, and personal preferences.

• Difficulty starting urination, a weak stream, urinary frequency, or nighttime urination
• Blood in the urine or semen
• Changes in erectile function
• Pelvic, back, hip, or other bone pain
• In advanced disease, leg weakness or numbness, urinary retention, weight loss, or anemia

Benign prostate enlargement and infection can cause similar urinary symptoms. Early prostate cancer is often asymptomatic.

• Increasing age
• A first-degree relative with prostate cancer
• Inherited variants involving BRCA2, BRCA1, HOXB13, or genes associated with Lynch syndrome
• Some ancestral populations experience a higher burden of diagnosis and aggressive disease; ancestry should not be treated as a deterministic biological label
• Obesity and metabolic health may influence the risk of aggressive disease
• Most cases cannot be attributed to one identifiable lifestyle cause

A detailed family history of prostate, breast, ovarian, pancreatic, and colorectal cancers can help determine whether genetic counseling is appropriate.

• PSA screening can reduce prostate cancer mortality in some populations but also creates false-positive results, overdiagnosis, and overtreatment.
• Screening decisions should use informed shared decision-making that considers age, family history, inherited risk, general health, and individual values.
• MRI, PSA density, and other risk tools may help reduce unnecessary biopsy in selected people, but they do not replace professional assessment.
• Vitamin E, selenium, or other supplements should not be promoted as proven prevention.
• Healthy weight, physical activity, not smoking, and a balanced diet support general health but cannot guarantee prevention.

Diagnosis is discussed within the Overview, Screening, Staging, and Biomarkers sections above for this cancer type. Specific tests depend on presentation, site, and pathology.

TNM describes local tumor extent, lymph nodes, and distant metastasis.

Gleason scoring combines the two dominant histologic patterns; modern reports often convert the result into Grade Group 1 through 5.

Risk classification also uses PSA, clinical stage, biopsy features, and sometimes imaging or genomic classifiers.

Metastatic disease may be described as castration-sensitive or castration-resistant, depending on whether it progresses despite a low-testosterone environment.

Androgen receptor signaling drives most prostate cancers. Progression can involve androgen receptor amplification or variants, PTEN loss and PI3K/AKT activation, homologous recombination repair defects, TP53/RB1 disruption, and neuroendocrine transformation.

Bone is a common site of metastasis. Molecular characteristics can differ between the original tumor and later metastatic sites.

• PSA for screening discussions, risk assessment, treatment response, and recurrence monitoring, but not as a cancer-specific test
• Gleason score and Grade Group
• Germline and tumor BRCA1/2, ATM, PALB2, and other homologous recombination repair genes
• MMR/MSI and selected high tumor mutational burden contexts
• PTEN loss and PI3K-AKT pathway alterations
• PSMA expression for molecular imaging and selection of some radioligand treatments
• Genomic classifiers that may add risk information in selected localized cancers

Biomarkers should be interpreted with stage, pathology, prior therapy, imaging, and the exact clinical question.

• BRCA1 / BRCA2
  Breast Cancer gene 1 and 2

• Very-low-risk, low-risk, and selected intermediate-risk localized disease: active surveillance can avoid or delay treatment-related harms.
• Localized or locally advanced disease: radical prostatectomy, external-beam radiation, brachytherapy, and, in some settings, androgen deprivation therapy.
• Biochemical recurrence: options depend on PSA kinetics, imaging, prior local treatment, and overall risk, and may include salvage radiation, systemic therapy, or observation.
• Metastatic castration-sensitive disease: androgen deprivation is commonly intensified with an androgen receptor pathway inhibitor and, for some patients, docetaxel.
• Metastatic castration-resistant disease: chemotherapy, PARP inhibitors, radioligand therapy, bone-targeted treatment, immunotherapy in selected biomarker-defined cases, and other targeted combinations.
• Palliative radiation can reduce pain or local compression from metastases.

• Androgen deprivation: GnRH agonists such as leuprolide; GnRH antagonists such as degarelix or relugolix
• Androgen receptor pathway therapy: abiraterone, enzalutamide, apalutamide, and darolutamide
• Chemotherapy: docetaxel and cabazitaxel
• PARP inhibitors and combinations: olaparib, rucaparib, talazoparib, or niraparib-containing strategies in defined molecular settings
• AKT pathway-directed therapy: capivasertib with abiraterone and prednisone for a specific PTEN-deficient metastatic U.S. indication
• Radioligand therapy: lutetium-177 vipivotide tetraxetan (PSMA-directed)
• Bone-related therapy: radium-223, zoledronic acid, or denosumab in defined settings
• Immunotherapy: sipuleucel-T or tumor-agnostic immune checkpoint indications in selected patients

• Surgery: urinary incontinence, erectile dysfunction, and surgical complications
• Radiation: urinary irritation, bowel symptoms, fatigue, and possible late sexual or gastrointestinal effects
• Androgen deprivation: hot flashes, bone loss, muscle loss, weight and metabolic changes, cardiovascular risk, and mood or cognitive effects
• Androgen receptor pathway drugs: fatigue, hypertension, falls, liver abnormalities, or electrolyte changes, depending on the drug
• Chemotherapy: bone marrow suppression, infection, neuropathy, and hair loss
• PARP inhibitors: anemia, fatigue, nausea, and rare marrow disorders
• Radioligand therapy: bone marrow suppression, dry mouth, and possible kidney effects
• Supportive care may include bone-density assessment, resistance and aerobic exercise, individualized calcium and vitamin D advice, cardiovascular risk management, pelvic-floor therapy, sexual health care, and psychosocial support.

New leg weakness, loss of bladder or bowel control, or severe new spinal pain may indicate spinal cord compression and needs urgent evaluation.

• PSMA PET and PSMA radioligand therapy are being studied in earlier disease settings and in new combinations.
• Germline and somatic DNA-repair testing is refining selection for PARP inhibitors.
• PTEN/AKT-directed combinations are expanding molecularly selected treatment.
• MRI-guided and transperineal biopsy strategies aim to improve detection while reducing infection and overdiagnosis.
• Circulating tumor DNA, circulating tumor cells, and molecular imaging are being studied as markers of resistance.
• Research is addressing neuroendocrine and androgen receptor-indifferent prostate cancer.
• A recent U.S. regulatory example is FDA approval on June 12, 2026, of capivasertib with abiraterone and prednisone for adults with metastatic androgen-pathway-modulation-naive or -sensitive prostate cancer that is PTEN-deficient by an FDA-authorized test.

• What are my Grade Group, PSA, TNM stage, and risk category?
• Should the biopsy be reviewed by a specialist, and do I need prostate MRI?
• Is active surveillance safe for me, and what would the surveillance plan include?
• How do surgery and radiation compare for cancer control, urinary, bowel, and sexual effects?
• Should I have germline or tumor genomic testing?
• Would PSMA PET change my treatment plan?
• Do I need androgen deprivation, and for how long?
• How will we protect bone, muscle, metabolic, and cardiovascular health?
• What options would be available if the cancer recurs or becomes metastatic?
• Are there clinical trials appropriate for my stage and molecular findings?