• Clinical science

Prostate cancer

Summary

Prostate cancer is the second most common cancer in men after skin cancer (malignant and nonmalignant melanoma) and the second leading cause of cancer death in men after lung cancer. The risk of developing prostate cancer increases with age. It is more common in African Americans. In early stages, prostate cancer generally causes no symptoms and is typically detected by screening. The preferred diagnostic procedures are digital rectal examination (DRE), PSA testing, and ultrasound-guided transrectal prostate biopsy. Bone metastases are common in advanced prostate cancer and can be diagnosed using a bone scan. Because most patients with prostate cancer are of advanced age, life expectancy and the histological evaluation of a tumor biopsy should be taken into account when planning treatment. Radical prostatectomy and radiotherapy are indicated in young patients. In older patients, “watchful waiting” (i.e., purely symptomatic treatment) and “active surveillance” (i.e., continuous restaging and initiation of curative measures if tumor progresses) are also a treatment option since localized prostate cancer typically has a slower growth rate and a better prognosis compared to other malignancies.

Epidemiology

  • Incidence: following skin cancer (i.e., melanoma and nonmelanoma combined) most common cancer in men in the US [1]
  • 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.

Etiology

Risk factors [2][3]

Advanced age is the main risk factor for prostate cancer.
Sexual activity and benign prostatic hyperplasia (BPH) are not associated with prostate cancer.

Classification

Clinical features

Early-stage prostate cancer

Advanced-stage prostate cancer

Constitutional symptoms

  • Fatigue
  • Loss of appetite
  • Weight loss

Urinary symptoms [5]

Metastatic disease

Diagnostics

Approach to suspected prostate cancer

Screening and basic diagnostics [6]

Digital rectal examination (DRE) [7]

  • Low sensitivity (approx. 30%)
  • Good specificity (approx. 90%) : Irregular and nodular prostate is suspicious for malignancy, but not specific for cancer.
  • Indications
  • Physiological DRE findings
    • Smooth
    • Nonfirm
    • Symmetric
    • Roughly heart-shaped
    • Painless
  • Early stage prostate cancer DRE findings
    • Localized indurated nodules
    • Otherwise smooth
    • Nonfirm
    • Painless
  • Advanced stage prostate cancer DRE findings
    • Asymmetric areas
    • Frank nodules
    • Painless

Blood tests

Prostate-specific antigen (PSA) levels

  • Overview
    • Serine protease that splits the semenogelin-1 protein and thereby liquefies semen.
    • Only produced by the prostate gland: organ-specific marker
  • Indication
    • Suspected prostate cancer
    • Screening
      • Benefit is controversial
      • Usefulness should be evaluated on a case-by-case basis by the physician and patient.
    • Monitoring of metastasis or detection of cancer recurrence following treatment of PSA-positive prostate cancer
  • Interpretation

Normal PSA values do not exclude the diagnosis of prostate cancer.

Inflammation, manipulation of the prostate, and other malignant or benign prostate disease causing elevated enzyme levels may lead to false-positive PSA results.

Other blood tests

Urine

Confirmatory testing

Prostate biopsy

  • Indication
    • Histological confirmation of suspicious findings on DRE
    • Suspicious PSA levels or velocities
    • Clinically suspicious prostate cancer
  • Technique: ∼ 12 prostate samples are taken from different areas of the prostate guided by transrectal ultrasonography (TRUS) under local anesthesia and prophylactic antibiotics.
  • Interpretation: : When prostate cancer is present in the biopsy, the tumor is graded using the Gleason score.
    • Calculated based on the microscopic appearance of prostate cancer
    • Higher score indicates a worse prognosis (ranges from 2 to 10)
    • Score is established by adding the Gleason grades of the most prevalent and the second most prevalent differentiation pattern within the biopsy
    • Grade ranges from 1 to 5
      • Grade 1: well-differentiated, microscopically uniform glands without invasion into adjacent healthy prostate tissue
      • Grade 5: undifferentiated cancer cells with no glandular differentiation
  • Complications

Staging

Indication

  • In confirmed prostate cancer to assess the extent of the disease
  • Should be performed, if advanced cancer is suspected by either PSA levels > 10 ng/mL or a Gleason score ≥ 7

Modalities

Pathology

Prostate cancer is commonly localized in the Peripheral zone (Posterior lobe).

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Approach

  • The treatment plan is based upon:
    • Patient's age
    • Life expectancy
    • Medical condition
    • Preferences
  • Results of imaging studies, PSA levels, and the Gleason score are taken into consideration when evaluating the different treatment options.

Management of localized disease

Active surveillance [12]

  • Regular follow-ups with cancer restaging instead of treatment
  • Preferred option for most early-stage cancers)
  • Treatment is only started if the tumor progresses.

Watchful waiting [12]

  • Less intensive type of follow-up than active surveillance
  • Best approach in a number of different cases, including:
    • Elderly patients with slow-growing tumors
    • Life-limiting comorbidity
    • Life expectancy < 10 years due to other causes
  • Systemic or local treatment to relieve symptoms is initiated if symptomatic progression of the tumor occurs.

Radiation therapy [13]

Radical prostatectomy [13]

Radical prostatectomy involves removal of the vas deferens, resulting in infertility.

Antiandrogen therapy [13]

  • Indication: androgen sensitive localized high-grade or metastatic prostate cancer
  • Methods
    • Medical castration: gonadotropin-releasing hormone (GnRH) agonists (e.g., leuprolide) or antagonist (e.g., degarelix)
      • May be combined with an antiandrogen (e.g., flutamide, bicalutamide) for complete androgen blockade.
      • Continuous administration of GnRH receptor agonists causes a transient increase in androgen levels during the first few weeks of therapy, followed by a sustained decrease.
    • Surgical castration

Management of disseminated disease

Management of castration-resistant prostate cancer (CRPC)

Detailed explanation of treatment

Complications

Metastasis

Complications following surgery or radiotherapy

Radiotherapy-specific risks

We list the most important complications. The selection is not exhaustive.

Prognosis

Survival rates of prostate cancer patients [15]
SEER Stage Description 5-year relative survival rate
Localized
  • Nearly 100%
Regional
  • Nearly 100%
Distant
  • 31%