Prostate cancer is one of the most common cancers that affect men, especially those > 50 years of age. Typically, prostate cancer has an indolent course and is usually discovered while still localized in the prostate. This allows many patients to undergo monitoring for progression rather than active treatment, preventing unnecessary treatment-related adverse effects. Prostate cancer is typically diagnosed and monitored using (PSA) testing, multiparametric MRI (mpMRI), and guided biopsy. Once the decision to treat has been made, therapeutic options include radical prostatectomy, radiation therapy, androgen deprivation therapy (ADT), and chemotherapy. Since all treatment options may adversely affect the patient's quality of life, with the patient is strongly encouraged in all current guidelines. Symptomatic management may be preferable in patients with significant comorbidities or limited life expectancy, as further treatment is unlikely to be life-prolonging.
- Incidence: following skin cancer (i.e., melanoma and nonmelanoma combined) most common cancer in men in the US 
- Mortality: in 2020, second leading cause of cancer deaths in men in the US (after lung cancer)
Epidemiological data refers to the US, unless otherwise specified.
- Advanced age (> 50 years) 
- Family history
- African-American descent
- Genetic disposition (e.g., BRCA2, Lynch syndrome)
- Typically asymptomatic
- Patients may present with features of (LUTS), including: 
Advanced prostate cancer can manifest with:
- Constitutional symptoms: fatigue, loss of appetite, clinically significant unintentional weight loss
- Features of metastatic disease; examples include:
Digital rectal examination (DRE) 
A DRE should be performed in individuals with elevated serum PSA levels; and as part of the comprehensive evaluation of male LUTS. DRE has a low positive predictive value for detecting prostate cancer and should not be performed as the sole screening modality.
- May be normal in early disease or if the cancer is located in areas of the gland that are not palpable on DRE 
Features suggestive of prostate cancer include:
- Localized indurated nodules on an otherwise smooth surface
- Prostatomegaly, lobar asymmetry, obliteration of the sulcus
- Hard nontender nodules
- Suspect prostate cancer in patients with elevated PSA levels detected on routine screening and/or abnormal findings on DRE.
- Consider adjunctive PSA testing (e.g., , , urinary levels) before performing a biopsy.
- Confirm the diagnosis on image-guided prostate biopsy.
- Stage prostate cancer to determine the appropriate management and prognosis.
Prostate-specific antigen (PSA) levels
- Total PSA levels
- Free PSA (unbound) : Free PSA levels are lower in prostate cancer than in normal prostate tissue or benign disease.
- Other causes of elevated total PSA: BPH, UTI, prostatitis, prostatic trauma or manipulation (including DRE) 
5-alpha reductase inhibitors (5-ARIs) can suppress PSA production, resulting in spuriously low PSA levels. This should be taken into consideration in patients on long-term 5-ARIs (e.g., for BPH). 
- Should be performed as part of the initial workup of LUTS and to rule out differential causes of elevated PSA
- Urinalysis is typically normal in patients with prostate cancer.
- Pyuria and/or bacteriuria in a patient with LUTS indicate a UTI or prostatitis.
mpMRI of the prostate 
- Becoming the preferred imaging modality for suspected prostate cancer 
- Additional indications include:
- Transrectal ultrasound of the prostate: predominantly used to guide prostate biopsy if there is clinical suspicion of prostate cancer 
- Indication: clinical suspicion of prostate cancer after shared decision-making with a patient whose life expectancy is ≥ 10 years 
Important considerations: Consider the following to minimize unnecessary biopsies. 
- Adjunctive PSA tests
- mpMRI of the prostate (if not already performed)
- Presence of
- Prostate cancer antigen 3 gene (PCA3) levels in urine 
- Prophylactic antibiotics to prevent prostatitis: recommended for transrectal biopsy; consider before transperitoneal biopsy
- Anesthesia: local anesthesia, nerve blocks, procedural sedation, or general anesthesia
- Under image guidance (TRUS-guided or MRI-guided), several biopsy cores are obtained from the prostate via the transperineal or transrectal approach. 
Findings: adenocarcinoma 
- Gleason grade: depending on the degree of differentiation of tumor cells and stromal invasion, tumors are graded from 1 (well-differentiated) to 5 (poorly differentiated)
- Gleason score (ranges from 2 to 10): the sum of the two most prevalent Gleason grades 
- Grade groups: prognostic categories based on the Gleason score that are used to guide management 
Evaluation of tumor extent 
- mpMRI provides information on local tumor extent (e.g., tumor size and volume).
- Additional imaging is recommended in patients with intermediate or high-risk prostate cancer to assess for local tumor extent and metastasis to guide management. 
- Cross-sectional imaging (CT, MRI, or PET-CT scan) is recommended to identify: 
Assessment of bone metastases
- Serum alkaline phosphatase may be elevated bone metastases.
- Bone scintigraphy (technetium-99m) is the standard study for detecting bone metastases. 
- PET scan is more sensitive than bone scintigraphy and may become the new standard. 
- X-rays (e.g., spinal x-ray) may be appropriate to evaluate undifferentiated bone pain or if pathological fractures are suspected.
mpMRI is the preferred method for detecting local tumor extent (including recurrent prostate cancer) and PET-CT is preferred to evaluate for metastatic disease. Skeletal metastases are the most common nonnodal sites of metastasis in prostate cancer. Vertebral metastases commonly occur due to the spread of malignant cells through the Batson vertebral venous system. Skeletal metastases are predominantly osteoblastic but osteolytic metastases can also occur.
The TNM staging system is based on American Joint Committee on Cancer recommendations (see “Grading and staging” in “General oncology”). Broadly, prostate cancer is divided into the following clinical stages. 
- Localized prostate cancer
- Locally advanced prostate cancer 
- Metastatic prostate cancer
Management options for prostate cancer depend on the cancer stage, presence of high-risk features, and the patient's life expectancy. The impact of potential adverse effects of treatment on quality of life should be discussed with the patient prior to treatment initiation.
- Estimate the patient's life expectancy.
to determine if it is localized, locally advanced, or
- Stratify risk based on the histological grade group and pretreatment PSA levels. :
- ADT PLUS androgen synthesis inhibitor PLUS radiation therapy :
- Anticipate and manage treatment-related complications (e.g., osteoporosis, pathological fractures, erectile dysfunction).
- Schedule follow-ups to assess response to therapy.
Watchful waiting 
- Indications: recommended approach if all of the following apply
Active surveillance 
- life expectancy > 5 years in patients with a
- May be considered in favorable
Androgen deprivation 
Androgen deprivation therapy (ADT)
- Definition: therapy designed to decrease testosterone production by the testes
- Adverse effects: increased risk of osteoporosis and fractures
- Indication: adjunct to ADT in locally advanced and metastatic prostate cancer
Androgen synthesis inhibitors
- Mechanism of action: inhibition of CYP17 gene products (including 17α-hydroxylase and 17,20-lyase) → inhibits androgen synthesis in the adrenal glands, testis, and tumor tissue
- Commonly used agent: abiraterone
- Specific adverse effects:
- Important consideration
- Androgen receptor antagonists (antiandrogen therapy)
Radiation therapy 
- Options: brachytherapy and/or external beam radiation therapy (EBRT)
Radical prostatectomy 
- Important consideration: PSA levels should drop to undetectable levels after a successful prostatectomy.
- Complications: erectile dysfunction; , urinary incontinence; , infertility 
- Indication: Consider as an adjunct to ADT in patients with metastatic prostate cancer.
- Commonly used agent: docetaxel (a cytotoxic agent)
Management of bone health 
Prophylaxis against treatment-induced osteoporosis and fractures
- Indications: patients on ADT, antiandrogens, and/or glucocorticoids
- Supplement calcium and vitamin D.
- Advice lifestyle modifications (e.g., smoking cessation, weight-bearing exercise).
- Assess fracture risk: assessment of bone mineral density (e.g., DEXA scan), assessment of 10-year fracture risk (e.g., using tools such as FRAX®)
- Consider osteoclast inhibitors (e.g., bisphosphonates, denosumab) in patients at high risk of a skeletal-related event.
- See “Prevention” in “Osteoporosis” for details.
Management of skeletal events 
- Pain due to skeletal metastases: Consider EBRT.
- Acute skeletal pain: urgent x-rays to assess for pathological fractures
- New neurological symptoms: urgent MRI spine to identify spinal cord compression (see “Acute back pain” for details)
- Monitor serum total PSA levels. 
- Every 6 months for the first 5 years, then annually for patients who have had definitive local therapy
- Every 3–6 months for patients on ADT
- Consider assessing PSA velocity (PSA doubling time); a significant rise or short doubling time suggests a recurrence. 
- Arrange further studies for patients with abnormal PSA values.
- Annual DRE: to monitor for prostate cancer recurrence and rectal cancer 
General principles 
Given the indolent nature of prostate cancer and the significant potential for treatment-related decline in quality of life, patients should be educated on the risks and benefits of participating in screening and undergoing treatment if cancer is detected. For patients with a limited life expectancy, neither screening nor treatment may be appropriate. 
- PSA screening is controversial as it has:
- Patient harm may occur as a result of testing and/or treatment initiated by a positive PSA screening test.
Screening recommendations 
|Screening recommendations by age group in prostate cancer |
|Patient age||Screening recommendation|
|< 40 years|| |
|40–54 years|| |
|55–69 years|| |
|≥70 years|| |
Screening modalities  
- PSA level remains the standard screening tool.
- DRE is not recommended as the sole screening tool for prostate cancer. 
- A screening interval of 2 years (or more) is recommended.
- Other tumors of the prostate
The differential diagnoses listed here are not exhaustive.