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

Age
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)
Lower urinary tract sx that suggest BPH
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 of SPA screening

Benefit	Key data
Reduced prostate-cancer mortality	ERSPC 16-year follow-up: 20 % relative reduction (RR 0.80) with an absolute reduction 0.18 % → ≈ 1 death prevented per 570 invitations
Fewer metastatic presentations	Serial screening halves the rate of metastatic disease at diagnosis
Curative window for localised disease	Surgery or RT can eradicate organ-confined cancers detected early
Active-surveillance pathway	Low-risk tumours can be monitored, avoiding or delaying radical therapy
Psychological reassurance	A normal PSA provides immediate peace-of-mind and usually averts further testing

⚠️ Potential Harms of SPA screening

Harm	Quantified impact
Over-diagnosis / over-treatment	Excess incidence ≈ 40–50 % of screen-detected cancers in AU modelling
False positives	6–7 % of men have a false-positive PSA at any round; only 25 % of biopsy specimens prove cancer
False negatives	PSA sensitivity ≈ 79–82 % overall (≈ 1 in 5 cancers missed); falls to ~72 % once PSA > 4 ng/mL (biological “PSA-poor” tumours)
Biopsy complications	• TRUS: infection/sepsis ≈ 1–3 %, rising hospitalisations noted up to 1.3 % Sperling Prostate Center • Transperineal: sepsis ≈ 0.1 % (infection <1 %) Grand Rounds in Urology
Treatment morbidity	• Erectile dysfunction 30–60 % after prostatectomy; 25–50 % after RT Hopkins Medicine • Urinary incontinence 5–35 % after prostatectomy; 5–10 % after RT Rajveer Purohit MD, MPH
Psychosocial & financial burden	Anxiety, insurance or employment implications; time off work for tests & treatment
Under-diagnosis of aggressive variants	Some high-grade cancers secrete little PSA and may be missed despite screening

📝 Key Clarifications for Shared Decision-Making

Screening target group: Australian guidelines (RACGP Red Book) support offering biennial PSA ± DRE to men 50–69 y (or 45–69 y with a 1st-degree FHx) after an informed discussion. RACGP
Absolute benefit is small: ≈ 1–2 prostate-cancer deaths avoided per 1000 men screened for 13–16 years. cancer.gov
Over-diagnosis substantial: About 3–4 indolent tumours detected for every lethal cancer prevented. RACGP
Biopsy route matters: Transperineal biopsy is now preferred in Australia owing to a 10-fold lower sepsis risk.
Modern management pathways (MRI-first triage, targeted biopsy, active surveillance) mitigate many historic harms, but surgery or RT still carry significant ED & incontinence rates.
False reassurance: A “normal” PSA does not exclude cancer—especially high-grade, PSA-poor tumours; ongoing symptom vigilance remains essential.

Investigations

Pre-Testing Considerations

Avoid PSA testing if:
- Active UTI, prostatitis, recent ejaculation (within 48 hrs), or DRE within the past week.
- Vigorous exercise (especially cycling) in the past 48 hrs.
Delay testing if symptoms suggest infection or recent urological procedures.

PSA Testing:

PSA is a glycoprotein enzyme produced by both benign and malignant prostate tissue.
used for
- Monitor known prostate cancer.
- Investigate symptoms: e.g. weak stream, haematuria, pelvic/back pain.
- Screening in asymptomatic men (with shared decision-making).

Limitations of PSA Testing

False Positives (Low Specificity)
- PSA can be elevated without cancer, reducing specificity.
- Specificity:
  - Overall: ~59%
  - PSA >4 ng/mL: ↑ to ~93%
Benign conditions causing elevated PSA:
- Benign prostatic hyperplasia (BPH)
- Prostatitis (bacterial or non-bacterial)
- Urinary tract infection (UTI)
- Recent ejaculation (within 48 hours)
- Prostate manipulation:
  - Digital rectal exam (DRE) (minor effect)
  - Cystoscopy
  - Prostate biopsy (significant rise)
  - Catheterisation or instrumentation
- Vigorous exercise, especially cycling or horse riding
- Acute urinary retention

False Negatives (Low Sensitivity)
- PSA can be normal in men with cancer.
- Drugs that lower PSA
  - Finasteride (5-alpha-reductase inhibitor)
  - Dutasteride
    - These drugs artificially lower PSA by ~50% after 6–12 months of use.
    - When interpreting PSA in men on finasteride or dutasteride, double the measured PSA value to estimate the true level.
- Sensitivity:
  - Overall: ~79–82%
  - PSA >4 ng/mL: drops to ~72%
- Up to 21% of cancers may be missed

‘PSA Showers’
- In BPH or subclinical prostatitis, the enlarged gland or chronic inflammation can intermittently release both free and bound PSA.
- PSA levels may fluctuate, especially in the “grey zone” (3–10 ng/mL):
- Requires re-testing after 6–12 weeks
- Consider free:total ratio, urine MCS, and DRE findings

eligability
- 1. Routine Screening (Average Risk)
  - Eligibility: Men aged 50–69 years without a significant family history or prior prostate disease.
  - Frequency: Once every 23 months.
- 2. High-Risk Individuals (Significant Family History)
  - Eligibility: Men with a first-degree relative (father, brother, or son) diagnosed with prostate cancer.
  - Frequency: Once every 11 months.
- 3. Monitoring Previously Diagnosed Prostatic Disease
  - Eligibility: Men with a history of prostate cancer, prostatitis, or premalignant conditions like atypical small acinar proliferation.
  - Frequency: No specific interval restrictions; testing as clinically indicated

Free-to-Total PSA Ratio:

Free PSA: Unbound form circulating in the blood.
Total PSA: Sum of both free and protein-bound PSA (mainly bound to α1-antichymotrypsin).

Physiological Differences

Type	Description	Half-Life	Clinical Relevance
Free PSA	Circulates unbound in plasma	2–3 hours	↑ in benign conditions (e.g., BPH, prostatitis)
Bound PSA	Attached to serum proteins	2–3 days	↑ in malignancy (e.g., prostate cancer)

In prostate cancer, a greater proportion of PSA is bound.
In BPH/prostatitis, more PSA circulates in free form.

How to Calculate

Free-to-Total PSA Ratio (%) = (Free PSA ÷ Total PSA) × 100

📌 Example:
Free PSA = 0.4 ng/mL, Total PSA = 5.0 ng/mL
→ Ratio = (0.4 ÷ 5.0) × 100 = 8%
→ High risk of prostate cancer → Refer to urology

Interpretation of Free:Total PSA Ratio

Ratio (%)	Interpretation	Estimated Risk of Cancer
>25%	Likely benign (BPH, prostatitis)	Low (~10%)
10–25%	Indeterminate zone	Moderate (~15–25%)
<10%	Suggestive of malignancy	High (~50–80%)
<8%	Strong predictor of cancer	Up to 80% PPV

⚠️ Ratios <10% are particularly concerning, especially when PSA is persistently elevated.

🧠 Clinical Context and Use

Best used when total PSA is mildly elevated (typically 3–10 ng/mL).

Helps differentiate between:
- Benign PSA elevation (e.g., BPH, prostatitis)
- Malignant elevation (e.g., prostate cancer)
Not a standalone diagnostic tool → used to guide:
- Further imaging (e.g., MRI)
- Referral for biopsy

Limitations and Pre-Testing Considerations

Free:Total ratio is only interpretable when PSA is elevated.

Affected by:
- Recent ejaculation
- Prostatitis
- Instrumentation (e.g., catheterisation, DRE)
Delay PSA testing for at least 6 weeks after resolution of these factors.
Adjust interpretation if prostate volume is known (used in risk calculators).

MBS – Eligibility Requirements for Free-to-Total PSA Ratio

Patient is asymptomatic, and
Age is ≥50 years, OR ≥40 years if there is a family history of prostate cancer (i.e. 1 first-degree relative diagnosed <65 years or 2 first-degree relatives at any age), and
Previous total PSA test result is between 3.0 and 10.0 ng/mL, and
No previous free PSA test in the last 12 months.

PSA Kinetics

Parameter	Description	Threshold
PSA Velocity	Rate of PSA rise over time	>0.75 ng/mL/year = ↑ Risk of malignancy
PSA Density	PSA divided by prostate volume (from TRUS or MRI)	>0.15 ng/mL/cm³ = ↑Risk – Suggests malignancy (requires prostate volume)
PSA Doubling Time	Time for PSA to double in value (used mainly in cancer follow-up)	Shorter = ↑ Aggressiveness

Next Steps Based on PSA Results

Initial PSA (MBS 66655)
│
├─ < 3.0 µg/L
│     └─ Reassure → repeat at 2 years
│
└─ ≥ 3.0 µg/L
      └─ Repeat same-lab PSA in 4–12 weeks
            │
            ├─ < 3.0 µg/L
            │     └─ Return to 2-yearly cycle
            │
            ├─ 3.0 – 5.5 µg/L
            │     ├─ %-free PSA (MBS 66659*)  
            │     └─ If %-free < 25 % **or** PSA rising
            │           └─ mpMRI prostate (MBS 63541) ± urology
            │                └─ Suspicious mpMRI → biopsy
            │
            ├─ > 5.5 – 10 µg/L
            │     ├─ Age < 70 y: %-free PSA usually self-funded  
            │     ├─ Age ≥ 70 y: %-free PSA rebate (66659 c)  
            │     └─ If repeat PSA still > 5.5 **or** %-free < 25 %
            │           └─ mpMRI (63541) → urology referral
            │
            └─ ≥ 10 µg/L
                  └─ Urgent urology referral (high-risk)  
                      └─ Repeat PSA only if it **will not delay** referral
* %-free PSA rebate rules: 
    age 50-69: total PSA 3.0-5.5 µg/L; 
    age ≥ 70: 5.5-10 µg/L; 
    one claim per 11 months.

Medicare Documentation Reminders

Indicate:
- Age group
- Family history
- Clinical rationale (symptoms, known disease)
Accurate documentation ensures appropriate MBS claiming and avoids out-of-pocket cost for patients.

Test Type	MBS Item	Eligibility Criteria	Frequency	Notes
1. Routine Screening – Average Risk	66655	– Men aged 50–69 years – asymptomatic – no significant family history.	Once every 23 months	Intended for population-based screening.
2. High-Risk Individuals – Family History	66654	– Men with a first-degree relative diagnosed with prostate cancer.	Once every 11 months	Higher screening frequency due to familial risk.
3. Ongoing Monitoring – Known Prostatic Disease	66656	– Men with a history of prostate cancer or – prostatitis or – premalignant conditions such as atypical small acinar proliferation.	As clinically indicated (no interval cap)	Does not include benign prostatic hyperplasia (BPH) alone anymore.
4. Elevated PSA in Asymptomatic Men	66659	No known prostatic disease AND: • Age 50–69: PSA >3.0 to ≤5.5 µg/L • Age ≥70: PSA >5.5 to ≤10.0 µg/L • Any age with family history: PSA >2.0 to ≤5.5 µg/L	Once every 11 months	Used to assess risk when PSA is elevated but without known disease.
5. Monitoring in Diagnosed Disease	66660	Known : prostatic disease AND meets the same PSA criteria as above: • Age 50–69: PSA >3.0 to ≤5.5 µg/L • Age ≥70: PSA >5.5 to ≤10.0 µg/L • Any age with family history: PSA >2.0 to ≤5.5 µg/L	Up to 4 tests every 11 months	For disease monitoring—allows more frequent testing.

Clinical Note: A free-to-total PSA ratio <10% is associated with a higher risk of prostate cancer.

Item 66655: Routine Screening – Average Risk Health.gov.au+7Health.gov.au+7Health.gov.au+7
Item 66654: High-Risk Individuals – Family History
Item 66656: Ongoing Monitoring – Known Prostatic Disease
Item 66659: Elevated PSA in Asymptomatic Men
Item 66660: Monitoring in Diagnosed Disease Health.gov.au+7Health.gov.au+7Health.gov.au+7

If you require further information or assistance, please let me know.

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%
- MEDICARE Eligibility:
  - For men aged <70 years with:
    - At least two PSA tests >3.0 ng/mL within 1–3 months, and
    - Free-to-total PSA ratio <25%, or
    - Repeat PSA >5.5 ng/mL.
- For men aged ≥70 years with:
  - At least two PSA tests >5.5 ng/mL within 1–3 months, and
  - Free-to-total PSA ratio <25%.
- Clinical Judgment: Always consider individual patient factors and clinical judgment when interpreting PSA results and determining the need for further investigations or referrals.

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

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