Prostate Cancer

Essentials of Diagnosis

• Prostatic induration on digital rectal examination (DRE) or elevated level of serum prostate-specific antigen (PSA)

• Most often asymptomatic

• Rarely, systemic symptoms (weight loss, bone pain)

General Considerations

• Most common cancer detected in American men

• Second leading cause of cancer-related death in men

• In the United States, in 2019, an estimated 174,650 new cases of prostate cancer were diagnosed, and 31,620 deaths resulted

• At autopsy, > 40% of men aged > 50 years have adenocarcinoma of the prostate, most often occult

• Incidence increases with age: autopsy incidence is ~30% of men aged 60–69 years versus 67% of men aged 80–89 years

• Risk factors

  • African American race

  • Family history of prostate cancer

  • History of high dietary fat intake

• A 50-year-old American man has lifetime risks of 40% for latent cancer, of 16% for clinically apparent cancer, and of 2.9% for death from prostate cancer

• Majority of prostate cancers are adenocarcinomas

Symptoms and Signs

• Discrete nodules or areas of induration within the prostate on DRE

• Obstructive voiding symptoms

• Lymph node metastases

• Lower extremity lymphedema

• Back pain or pathologic fractures

• Rarely, signs of urinary retention (palpable bladder) or neurologic symptoms as a result of epidural metastases and spinal cord compression

Laboratory Tests

• The serum PSA level is typically low and correlates with the total volume of prostate tissue and tends to increase with age

• Measurement of serum PSA is useful in

  • Detecting and staging prostate cancer

  • Monitoring response to treatment

  • Identifying recurrence before it becomes clinically evident

• As a screening test, PSA is elevated (> 4.0 ng/mL [4.0 mcg/L]) in 10–15% of men

• Approximately 18–30% of men with PSA 4.1–10 ng/mL (4.1–10 mcg/L) and 50–70% of men with PSA > 10 ng/mL (10 mcg/L) will be diagnosed with prostate cancer

• Patients with PSA levels < 10 ng/mL (10 mcg/L) usually have localized and therefore potentially curable cancers

• Patients with PSA levels > 40 ng/mL (40 mcg/L) are more likely to have advanced disease (seminal vesicle invasion, lymph node involvement, or occult distant metastases)

Imaging Studies

• Transrectal ultrasound (TRUS): most prostate cancers are hypoechoic

• CT of the abdomen and pelvis and radionuclide (99-technetium) bone scans are generally the first-line staging studies performed, when indicated, to assess for nodal and bony metastases, respectively

• MRI of the prostate

• CT imaging can be useful in detecting regional lymphatic and intra-abdominal metastases

• Conventional radionuclide (99-technetium) bone scan is recommended for patients with a PSA level > 20 ng/mL

• PET (eg, ¹⁸F-sodium fluoride [¹⁸F-NaF] PET) and hybrid [¹⁸F-NaF] PET/CT imaging appear to be more sensitive than conventional bone scans

• Fluciclovine (Axumin) PET imaging has been approved for suspected cancer recurrence based on elevated PSA after prior treatment

• PSMA (prostate-specific membrane antigen) PET, using small molecules radiotracers targeting PSMA (eg, ¹⁸F-DCFBC (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-¹⁸F-fluorobenzyl-L-cysteine)

  • Have shown significant promise as next-generation imaging agents

  • May replace traditional imaging modalities in the future

Diagnostic Procedures

• TRUS-guided biopsy from the apex, mid portion, and base of the prostate

  • Done in men who have an abnormal DRE or an elevated PSA level

  • Systematic, rather than only lesion-directed, biopsies are recommended

  • Extended pattern biopsies, including a total of at least 10 biopsies, are associated with improved cancer detection and risk stratification of newly diagnosed patients

• MRI-guided biopsy may improve not only overall cancer detection but discovery of clinically relevant disease

• Newer tests, including the Prostate Health Index (PHI) and 4kscore (4kscore.com), may better identify not only men at greater risk for prostate cancer but those with more aggressive disease

• Genetic testing

  • A family history of prostate cancer increases the risk of prostate cancer

  • Prostate cancer has been associated with several hereditary cancer syndromes (eg, Lynch syndrome, hereditary breast and ovarian cancer syndrome, etc.) with approximately 11% of prostate cancer patients with at least one additional primary cancer carrying germline mutations

  • Consequently, some patients with prostate cancer and their families may have elevated risk for other cancers

General Measures

• Patients need to be advised of all treatment options (including active surveillance or "watchful waiting") and their benefits, risks, and limitations

• The goal of active surveillance is to avoid treatment in men who never experience disease progression while recognizing and effectively treating men with evidence of progression

• For localized disease

  • Optimal management is controversial because of

    • Plethora of treatment options

    • Side effects of various options

    • Indolent nature of many prostate cancers

  • To help guide treatment decision making, patients are risk stratified according to

    • PSA level at diagnosis

    • DRE

    • Prostate cancer grade (Gleason score)

  • Patients should have an assessment of life expectancy prior to treatment decision-making since all patients with low-risk disease and many with intermediate-risk disease with < 10-year life expectancy will not benefit from treatment

• Focal therapy

  • Delivers energy to a patient's prostate to destroy his tumor(s) and a margin of normal prostate tissue while avoiding treatment of the entire gland to avoid collateral damage to the neurovascular bundles, external urinary sphincter, bladder, and rectum

  • To date, several energy sources (cryotherapy, high intensity focused ultrasound, lasers, etc.) have been evaluated and several others are under development

Medications

• Androgen deprivation therapy may be effective at several levels along the pituitary–gonadal axis using a variety of methods or agents (Table 39–10)

Surgery

• Radical prostatectomy

  • For stages T1 and T2 prostatic cancers, local recurrence is uncommon after radical prostatectomy

    • Organ-confined cancers rarely recur

    • Locally extensive cancers (capsular penetration, seminal vesicle invasion) have higher local (10–25%) and distant (20–50%) relapse rates

  • Adjuvant therapy (radiation for patients with positive surgical margins or androgen deprivation therapy for lymph node metastases)

Therapeutic Procedures

• Radiation therapy

  • External beam radiotherapy

  • Transperineal implantation of radioisotopes

• Newer techniques of radiation (implantation, conformal therapy using three-dimensional reconstruction of CT-based tumor volumes, heavy particle, charged particle, and heavy charged particle) improve local control rates

• Brachytherapy is implantation of permanent or temporary radioactive sources (palladium, iodine, or iridium)

• For locally extensive cancers, including seminal vesicle and bladder neck invasion, combination therapy (androgen deprivation combined with surgery or radiation therapy)

Prognosis

• Morbidity is limited; survival with localized cancers is 65% at 10 years

• Widely used nomograms include the Kattan nomogram and the CAPRA nomogram

  • CAPRA uses serum PSA, Gleason score, clinical stage, percent positive biopsies, and patient age in a point system to risk stratify and predict the likelihood of PSA recurrence 3 and 5 years after radical prostatectomy as well as metastasis and prostate cancer-specific and overall survival

  • CAPRA nomogram has been validated on large multicenter and international radical prostatectomy and radiation-treated cohorts

Prevention

SCREENING FOR PROSTATE CANCER

• Screening tests currently available include DRE, serum PSA, TRUS

  • Detection rates with DRE are low, varying from 1.5% to 7.0%

  • TRUS has low specificity (and therefore high biopsy rate)

  • TRUS increases the detection rate very little when compared with the combined use of DRE and serum PSA testing

• To improve the performance of serum PSA as a screening test, alternative methods for its use have been developed

  • Establishment of age- and race-specific PSA reference ranges

  • Measurement of free serum and protein-bound levels of PSA

  • Calculation of changes in PSA over time (PSA velocity)

• Traditional yearly screening may not be the most efficient approach, rather, earlier PSA testing at younger ages may provide information regarding PSA velocity and allow less frequent testing

  • Men with PSA levels above the age-based median when tested between ages 40 and 60 years are at significantly increased risk of cancer detection over the subsequent 25 years

  • Men aged 40–50 with PSA < 0.6 ng/mL [0.6 mcg/L] and aged 50–60 with PSA < 0.71 ng/mL [0.71 mcg/L] may require less frequent PSA tests

  • In addition, men with PSA velocity > 0.35 ng/mL per year measured 10–15 years before the diagnosis of cancer had significantly worse cancer-specific survival compared with those with lower PSA velocity

• The National Comprehensive Cancer Network guidelines (https://www.nccn.org/professionals/physician_gls/f_guidelines.asp) for early detection of prostate cancer incorporate many of these factors (eFigure 39–9)

When to Refer

• Refer all patients with localized disease to a urologist for active surveillance or management

  • Active surveillance may be appropriate in selected patients with very low volume, low-grade prostate cancer

  • Management of localized disease may be by surgery or radiation therapy

• Locally extensive, regionally advanced and metastatic disease often require multimodal treatment strategies

• For metastatic disease, medical oncology should be consulted for consideration of systemic treatments