Epidemiology and Etiology
Prostate cancer is the most common cancer in men in the United States, with an estimated 164,690 new cases and 29,430 deaths in 2018. African American ethnicity, family history, age, and a high-fat/low-vegetable diet are common predisposing risk factors.
The absolute risk reduction in mortality from annual prostate-specific antigen (PSA) is modest and should be discussed with patients older than 50 years of age with known risk factors. The USPSTF currently recommends selective PSA-based screening for men aged 55–69, after a thorough conversation of the potential risks and benefits of screening. There are conflicting data from American and European trials looking at the benefit of prostate cancer screening.
The most common presentation in the United States is asymptomatic elevation in PSA. Digital rectal examination (DRE) findings of asymmetric induration or nodules are suggestive, and any palpable nodule should be biopsied. Less common symptoms are obstructive symptoms, new-onset erectile dysfunction, hematuria, or hematospermia. Bone is the most common site of metastatic involvement, and patients with skeletal metastases can present with pain, fractures, and nerve root compression.
DRE supplemented by transrectal ultrasound-guided biopsy helps in assessing T stage. PSA testing and Gleason scoring in the initial biopsy are important in staging and risk category assessment. Although patients with high-risk disease are likely to benefit from routine imaging (CT, MRI, or bone scan) for detection of metastatic disease, symptom-directed imaging is appropriate in patients with low-risk disease.
- Gleason grades range from 1 to 5. Typically, clinically relevant cancers are scored from grade 3 (well-differentiated) to grade 5 (poorly differentiated) gland pattern. Gleason score is the sum of the grades for the primary and secondary patterns seen on the biopsy. Overall scores of 6 indicate low-risk, 7 indicate intermediate-risk, and 8+ indicate high-risk histologies.
- Risk categorization: Based on these characteristics, tumors are classified as low (PSA ≤10 ng/mL, Gleason score <7, and stage up to T2a), intermediate (PSA >10 to ≤20 ng/mL, Gleason score 7, and stage T2b), or high (PSA >20 ng/mL, Gleason score >7, and stage T2c) risk.
Early stage disease (T1–T2) is confined to the prostate, and locally advanced disease (T3–T4) is defined by local invasion. Stage IV disease is defined by nodal involvement (N1) and metastatic disease (M1).
The most important predictors of outcome are pretreatment PSA levels, Gleason score, and clinical TNM stage.
- Early stage disease: Outcomes are equivalent between radical prostatectomy, external-beam radiation, or brachytherapy, although brachytherapy alone is not recommended in higher-risk disease. Late toxicities are variable but usually include incontinence and erectile dysfunction. Active surveillance is a suitable option for men with low-risk disease.
- Locally advanced disease is often treated with different combinations of surgical, radiation, and hormonal therapy. Surgery (if previous radiation), radiation (if previous prostatectomy), brachytherapy, and sometimes systemic hormonal therapy can be considered in patients who show an asymptomatic increase in PSA levels after surgery or radiation. The question of adjuvant (soon after surgery) or “salvage” (at time of PSA recurrence) radiation superiority is currently being studied in randomized, prospective trials.
- Metastatic disease is incurable and is initially treated with surgical or medical castration with an LHRH receptor agonist or antagonist, termed androgen deprivation therapy (ADT), because testosterone/androgens play a major role in tumor growth. The antiandrogens flutamide or bicalutamide may be added for combined androgen blockade, which has shown marginal improvements in overall survival compared with LHRH monotherapy in meta-analyses.
- ADT in combination with chemotherapy or abiraterone is active and useful in treating select patients with high-risk/high-volume metastatic prostate cancer that is castration sensitive.1,2,3
- Castration-resistant disease is diagnosed in patients who experience disease progression on ADT therapy. Chemotherapy with docetaxel, cabazitaxel, or therapy with abiraterone, enzalutamide, radium-223, and sipuleucel-T are effective options for these patients. Sipuleucel-T is an autologous cell-based vaccine targeting prostatic acid phosphatase.4
- Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352-360. doi:10.1056/NEJMoa1704174. [PMID:28578607]
- James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338-351. doi:10.1056/NEJMoa1702900. [PMID:28578639]
- Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737-746. doi:10.1056/NEJMoa1503747. [PMID:26244877]
- Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422. doi:10.1056/NEJMoa1001294. [PMID:20818862]
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