History and exam
Key diagnostic factors
common
elevated prostate-specific antigen (PSA)
Most common presenting finding.
Elevated PSA levels should be correlated with patient age as PSA typically increases with age regardless of presence of prostate cancer.[58]
Other nonmalignant conditions (e.g., prostatitis and benign prostatic hyperplasia) may increase PSA levels. PSA levels may also vary according to race.[51]
Other diagnostic factors
common
abnormal digital rectal exam (DRE)
Less common presenting finding since prostate-specific antigen (PSA) screening has been widely adopted.
An asymmetric and/or indurated or nodular prostate suggests cancer and should prompt further evaluation.
The overall size of the prostate may be noted. However, estimating the size of the prostate on exam is inaccurate and unreliable.
uncommon
nocturia
Uncommon in low-risk (early-stage) disease. If present, may indicate more advanced disease or (more commonly) benign prostatic hyperplasia.
urinary frequency
Uncommon in low-risk (early-stage) disease. If present, may indicate more advanced disease or (more commonly) benign prostatic hyperplasia.
urinary hesitancy
Uncommon in low-risk (early-stage) disease. If present, may indicate more advanced disease or (more commonly) benign prostatic hyperplasia.
dysuria
Uncommon in low-risk (early-stage) disease. If present, may indicate more advanced disease or (more commonly) benign prostatic hyperplasia.
hematuria
Uncommon in low-risk (early-stage) disease. If present, may indicate more advanced disease or (more commonly) another unrelated urinary tract disorder.
weight loss/anorexia
Associated with metastatic disease.
lethargy
Associated with metastatic disease.
bone pain
Associated with metastatic disease.
palpable lymph nodes
Associated with metastatic disease.
Risk factors
strong
age >50 years
Of the known risk factors for prostate cancer, age is the most important.[30][31] It is most commonly reported in men ages over 50 years; median age at diagnosis is 67 years (based on 2017-2021 data).[1]
Autopsy data indicate that 70% of men over 80 years of age and 40% of men over 50 years of age have pathologic evidence of prostate cancer.[32]
black ethnicity
The incidence of prostate cancer in the US is highest among non-Hispanic black men (188.7 per 100,000).[1] in the US, non-Hispanic black men are twice as likely to die of the disease compared with other ethnicities (including non-Hispanic white, non-Hispanic American Indian/Alaska Native, non-Hispanic Asian/Pacific Islander, and Hispanic).[1]
In the UK, incidence rates for prostate cancer are approximately twice as high in black men (African, Caribbean, or other black ancestry) compared with white men, and peak at a younger age (2.9 times higher in black men ages <65 years and 1.9 times higher in those ages ≥65 years, based on data from 2013 to 2017). [11]
Analysis of incidence data suggests that black men have a higher risk of developing preclinical prostate cancer and a higher risk of progression to metastatic disease.[25][26] However, differences in survival may be related to social determinants of health rather than race or genetic risk factors.[26][33][34]
Northwest European, Caribbean, Australian, New Zealand, North American, and Southern African populations
Incidence is highest in northwest Europe, the Caribbean, Australia, New Zealand, North America, and Southern Africa.[8]
positive family history/genetic factors
Risk of prostate cancer is increased in men with a positive family history of prostate cancer.[20] One meta-analysis reported a pooled relative risk (RR) of 2.48 in men with one first-degree relative (brother or father) with prostate cancer compared with no first-degree family history.[20] Risk was higher if the first-degree relative was a brother (RR 3.14) than a father (RR 2.35). A RR of 4.39 was reported in men with two or more first-degree relatives with a history of prostate cancer.
The genetic basis for this hereditary cause is unclear, but prostate-cancer specific germline mutations (e.g., HOXB13) have been implicated.[21] Germline mutations that increase the risk of prostate and other cancers have been identified:
Homologous recombination DNA repair gene mutations (e.g., BRCA1, BRCA2, ATM, CHEK2, PALB2, RAD51D)
DNA mismatch repair gene mutations (e.g., MLH1, MSH2, PMS2, MSH6)
Germline BRCA mutations are associated with a high risk of early-onset prostate cancer, more aggressive disease, and poor survival outcomes.[35][36]
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