Prostate cancer / Prostate cancer screening

Symptoms of prostate cancer

• Most patients have no symptoms.
• Some patients may complain of :
  • lower urinary tract symptoms (LUTS)
    • 70% bladder outlet obstruction
      • hesitancy
      • frequency
      • urgency
      • nocturia
      • slow interrupted flow
      • terminal dribbling
    • These are most often due to benign prostatic hyperplasia, which may coexist with prostate cancer
• OR
  • metastatic spread (esp to bone)
    • Bone pain, weight loss, lower back pain, and haematuria are uncommon presentations.
      • 25% acute retention
      • 15% back pain
      • 5% haematuria
      • 5% uraemia
      • OTHER tiredness, wt loss, perineal pain

History/Risk factors

1. Age
2. Fhx of prostate cancer
   • Lower age at diagnosis of relative(s)
   • ≥ 1 first-degree relative with prostate cancer especially if aged < 65 years (affected brother indicates higher risk than affected father)
   • Hereditary breast or ovarian cancer (association with BRCA gene)
   • Lynch syndrome (HNPCC)
3. Lower urinary tract sx that suggest BPH
4. Red flag symptoms eg. Weight loss, bone pain, haematuria

EXAMINATION

• DRE:
  • In asymptomatic men interested in undergoing testing for early diagnosis of prostate cancer, digital rectal examination is not recommended as a routine addition to PSA testing in the primary care setting.
  • Test Sensitivity: <60%
  • Test Specificity: >83%
  • Positive Predictive Value: <28%
  • DRE may be normal even if prostate Ca.
  • Abnormal findings =
    • Hard lump (50% hard lumps will NOT be cancer)
    • Asymmetry
    • Induration
    • Loss of median sulcus

PSA screening

Key organisation’s positions on PSA testing:

• RACGP:
  • Population-based screening is not recommended.
  • If the patient requests screening and is fully counselled about the risks and benefits, offer a PSA blood test.
• Prostate Cancer Foundation of Australia and Cancer Council Australia, approved by National Health and Medical Research Council (NHMRC – wiki.cancer.org.au):
  • Population screening is not recommended
  • Do not offer PSA testing at age 40 years to predict risk of prostate cancer death
  • PSA testing is not recommended for men who are unlikely to live another 7 years
  • For men at average risk who understand the benefits and harms, and who decide to undergo regular testing for prostate cancer,: offer PSA testing every 2 years from age 50 to 69 years.
  • offer further investigation if total PSA is greater than 3.0 ng/mL.
• Urological Society of Australia and New Zealand (USANZ):
  • USANZ endorse the Prostate Cancer Foundation Of Australia (PCFA) guidelines.
  • For men aged 50 to 69 years, PSA testing reduces the incidence of metastatic prostate cancer and prostate cancer specific mortality.

RED BOOK v10:

target group	Screening/Intervention	frequency of Ix	intervention
50–69 years at average* risk	PSA testing Digital rectal examination – not recommended as a routine addition to PSA testing in asymptomatic men	every 2 ys	Average = Men without family history initial total PSA >3.0 ng/mL, offer repeat PSA within 1–3 months initial total PSA >3.0 – 5.5 ng/mL, measure free-to-total PSA percentage at the same time as repeating the total PSA. Offer further investigation if total PSA is greater than 3.0 ng/mL.
45-69 years at moderate* risk	PSA testing	every 2 yrs	Moderate = Men with a brother or multiple first-degree relatives diagnosed with prostate cancer
40-69 year at high* risk	PSA testing	every 2 yrs	High = Men with three affected 1st-degree relatives diagnosed with prostate cancer
men aged ≥70 years	Shared decision-making		– Harms of PSA testing, such as overdiagnosis, unnecessary treatment, and quality-of-life issues (e.g., incontinence, erectile dysfunction) should be discussed – Men who are likely to live less than another 7 years is not recommended

Potential benefits

1. Reassurance if the test is normal or very low
2. Early detection of prostate cancer may mean that early treatment can potentially cure the disease & avoid disability or decreased life expectancy as a result of the cancer

Potential harms

1. If prostate cancer is found to be present after an abnormal PSA test, the following issues may arise:
   • some prostate cancers are latent and slow growing, and do not require treatment (overdiagnosis and possibly over treatment)
   • some prostate cancers are incurable,even with early detection (underdiagnosis)
2. Risk of false positives leading to further investigations with ultimately no cancer found
3. Risk of false negatives meaning that patient is falsely reassured
4. Further Investigations prompted by a raised PSA can cause harm
   • Possible complications of biopsy
     • Bleeding – urethral, rectal, or haematospermia
     • Infection of bladder or prostate
     • Sepsis – 1 in 1000 risk (TRUS biopsy 2 to 3%, transperineal biopsy 1 in 1000)
     • Urinary retention
   • possible complications of prostatectomy
     • impotence/erectile dysfunction
     • incontinence

Investigations

• before testing important to advise men to:
  • avoid ejaculation, either by masturbation or intercourse, for 48 hours prior to testing
  • Long-distance bike riding should also be avoided
• PSA
  • a PSA test can be abnormal when cancer is not present – (False positives, ie low Specificity)
    • Specificity: Overall: 59% (93% for a PSA >4 ng/ml)
  • a PSA test can be normal even when cancer is present ( False negatives, ie: low Sensitivity)
    • Sensitivity: : 79-82% (72% for a PSA >4 ng/ml), can miss up to 21% of cancers
  • Investigation suggestions:
    • If age 50-69yrs, If PSA 3 to 10 nanograms/mL, or other reversible cause for PSA elevation suspected
      • Repeat PSA in 1 to 3 months 
      • (at least 6 weeks after treating reversible causes) 
      • If PSA persistently elevated- Request non-acute urology assessment.
    • If age 50-69yrs, If initial PSA was 3 to 5.5 nanograms/mL
      • request free‑to‑total PSA ratio in addition to repeat PSA.
      • PSA ratio measures the % of free (unbound) PSA & expresses this as a ratio compared to total amount of PSA. 
      • In prostate Ca most of the PSA is bound so the ratio is lower, ie: if >25% risk of Ca is low
    • If age 50-69yrs, If PSA ≥ 10 nanograms/mL and other causes for PSA elevation ruled out:
      • If not already done, arrange additional investigations including FBC, ELFT, MSU 
      • microscopy, culture, and sensitivities, and ultrasound of the urinary tract.
      • inform the patient about the implications of test results and indication for referral.
      • Request non-acute urology assessment (mark referral as urgent)
• Free: total PSA ratio
  • Men with constantly elevated PSA concentrations (but below 10 microgram/L) should have the free to total PSA ratio estimated
  • Under Medicare:
    • At least one free to total PSA ratio can be requested each year when the PSA is above the median.
    • Should the PSA concentrations be above the agerelated upper limit, several PSA tests and up to 4 free to total PSA ratios can be requested within each year.
  • free PSA has a short half-life (2–3 hours), A are not bound to protein, and are not active
  • bound PSA has a long half-life (2–3 days)
  • Patients who have diseases that cause:
    • intermittent ‘showers’ of PSA – ie: BPH where intermittent physical disturbance of the enlarged gland or the increased risk of intermittent subclinical prostatitis:
      • will have both free and bound PSA
      • if ratio is >25% risk of Ca is low
    • chronic release of PSA – ie: Cancer with continuously progressive disease with PSA release:
      • bound PSA will accumulate in the blood due to its longer half-life compared to free PSA.
      • example: less than 10% free PSA, more than 90% bound PSA: ie: low free to total PSA ratios
      • If the free to total PSA ratio is below 8%, the risk of prostate cancer is almost 80%
• PSA velocity

Factors that contribute to ­ elevated PSA

1. BPH
2. Prostate Cancer
3. Prostatitis
4. Recent sexual activity/ejaculation w/in 48hrs
5. Virogrous physical exercise within 48hrs
6. Prostatic biopsy w/in 6 weeks
7. Active UTI
8. DRE w/in 1/52

PSA levels for different age groups

Imaging

• Ultrasound
  • Transrectal ultrasound (TRUS) – minimally invasive procedure
  • Sensitivity: TRUS-guided biopsy detects about 48-60% of clinically significant prostate cancers, limited sensitivity for detecting prostate cancer, especially for smaller or non-palpable lesions.
  • Specificity: 60-70%, with many benign conditions mimicking cancer on ultrasound, may have difficulty distinguishing between benign conditions (e.g., prostatitis, benign prostatic hyperplasia) and cancer, leading to more false positives.
• multiparametric MRI (mpMRI)
  • more accurate in detecting clinically significant prostate cancer
  • can help reduce the number of unnecessary biopsies by more accurately identifying men who need further investigation
  • Sensitivity: 85-93%
  • Specificity: ranges from 89-94%

TREATMENT

Localized Prostate Cancer (stage A to C)

• Watch + wait =
  1. if — PSA ≤ 20 ng/mL — clinical stage T1–2 — Gleason score 6
  2. If unlikely to live another 7 years (subject to health status).
• Radical Prostatectomy
  • usually <70 & PSA <20
  • Long-term cure rate (80%)
  • has to be balanced against urinary incontinence in 10% (sufficient to need pad) & impotence in 70%.
• Radiotherapy = Lower Incidence of Sexual Dysfunction and Urinary Incontinence post-procedure
  • External Beam Prostate Radiotherapy
    • not as good cure rate as surg but difference doesn’t become apparent until 10yrs. SE faecal urgency, diar + impotence after 2yrs
    • advantage is can be performed in pt’s unfit for surgery
  • Prostate Seed Implant Radiotherapy (Brachytherapy)

Advanced Prostate Cancer (stage D)

• Endocrine agents primarily lower Testosterone Levels
• Adverse effects: Hot Flashes, Erectile Dysfunction, Metabolic Syndrome, Muscle loss, Osteoporosis. loss of sexual desire, growth of breast tissue, Weight gain 
• LHRH agonists
  • Suppress Testosterone: example: Goserelin acetate (Zoladex), Leuprolide acetate (Lupron)
• Antiandrogens
  • Enzalutamide (Xtandi)
• Bilateral Orchiectomy
  • = often psychologically unacceptable
• Diethylstilbesterol (DES) 1 to 3 mg daily

Treatment COMPLICATIONS

Impotence/Erectile Dysfunction:

• Treatment Options:
  • Sildenafil (Viagra): Often the first-line treatment
    • Success Rates:
      • After surgery: (TURP or prostatectomy): 30-40% success, depending on nerve-sparing status.
      • After radiotherapy: 80-100% success, although some data suggest that radiation can also affect erectile function over time.
  • Penile injections: Alprostadil (Caverject) or a combination (Trimix) can be effective.
  • Vacuum devices: Useful for achieving erections mechanically.
  • Penile implants: Considered when other treatments fail

Orgasm and Ejaculation:

• Orgasm achievable: Yes, most men can achieve orgasm after these procedures, but ejaculation is usually absent due to retrograde ejaculation (post-TURP) or dry orgasms (after prostatectomy or radiation).

Rectal Problems (Post-Radiation):

• Proctitis: Inflammation of the rectum post-radiation can be managed with:
  • Corticosteroid enema: Predsol Enema is appropriate.
  • Chronic rectal bleeding: Treated with topical formalin or laser therapy if conservative management fails.

Urinary Incontinence:

• Management:
  • Pelvic floor exercises:
    • first-line treatment
    • Typically recommended for 6-12 months post-surgery.
  • Persistent incontinence:
    • Collagen injections: Can be used, but the success rate is variable.
    • Surgical options: If incontinence persists, an artificial urinary sphincter is a common and effective surgical option.

shortcode for consent:

Discussion Summary: The patient was informed about the benefits and risks of PSA testing for prostate cancer screening. Benefits of Early Detection: PSA testing can detect prostate cancer before symptoms develop, increasing the chance of early treatment. Early treatment typically has fewer side effects and can prevent cancer from spreading, which is harder to treat in advanced stages. A low PSA level (<1 ng/ml) with a normal exam is reassuring. Risks of PSA Testing: PSA levels can be abnormal without cancer (false positives), leading to unnecessary worry or testing. Some prostate cancers grow slowly and may not need treatment. A biopsy, if needed, carries a small risk of infection, and treatment decisions can be complex. Potential Side Effects of Treatment: Treatment options for prostate cancer may lead to issues with erection, urinary, and bowel function, but these have improved with modern techniques. Next Steps: If the PSA, further monitoring, repeat testing, or a biopsy may be required. If cancer is detected, treatment options will be discussed. Patient’s Decision: ☐ Proceed with PSA testing ☐ Decline PSA testing