Makindo Medical Notes

Related Subjects: | Urothelial Tumours | Haematuria | Acute Urinary Retention | Anuria and Oliguria | Bladder Cancer | Renal Cell Carcinoma | Benign Prostatic Hyperplasia | IgA Nephropathy | Prostate Cancer | Henoch-Schonlein Purpura | Glomerulonephritis

🧪 PSA (Prostate-Specific Antigen) is elevated in various prostate diseases. 📈 PSA velocity = rate of PSA change over time. 🦴 PSA >100 ng/mL usually suggests bony involvement. ✋ Rectal exam does not significantly raise PSA. ⚗️ PSA is a 34 kDa glycoprotein protease secreted by epithelial cells of the prostate acini, helping liquefy semen. 🔺 Elevated PSA may reflect prostate cancer, BPH, ageing, post-ejaculation, or prostate calculi.

📌 About Prostate Cancer

• 🧓 Often detected incidentally at post-mortem >70 yrs.
• ⚖️ Main challenge = when to screen and when to treat.
• 🔍 Screening has not consistently shown survival benefit.
• 💉 Cancer growth is testosterone-dependent.

📊 Epidemiology

• 🇬🇧 UK: ~41,700 new cases/year.
• 📉 Only 1% diagnosed <50 yrs.
• 🏿 Higher prevalence in Black African/Caribbean men.
• 👨 Family history ↑ risk ×3.5.
• 🚬 Smoking + ⚖️ obesity linked to more aggressive disease.

🧫 Pathology

• 95% = acinar adenocarcinoma from glandular epithelium.
• 5% = squamous, transitional or rare variants.
• 📍 Most arise in the peripheral zone.
• 🔺 PIN (Prostatic Intraepithelial Neoplasia) = precursor lesion.
• 🧪 PSA + acid phosphatase secreted by prostate epithelium.

🩺 Clinical Presentation

• 💧 LUTS: frequency, nocturia, weak stream, dribbling.
• 🦴 Bone pain or pathological fracture = likely metastasis.

🧩 Common Presentations

• 📈 Raised PSA (screening or post-TURP histology).
• ✋ DRE: hard, craggy prostate, loss of median sulcus.
• 🚽 Outflow obstruction → renal impairment.
• 🦴 Osteosclerotic mets → pain, fracture.
• Advanced: haematuria, haematospermia, obstruction.

📐 PSA Reference Ranges

• 👨 <50 yrs: <3 ng/mL.
• 60–69 yrs: <4 ng/mL.
• >70 yrs: <5 ng/mL.
• <10 ng/mL: usually BPH/prostatitis, but cancer in 20%.
• >10 ng/mL: ~50% chance of malignancy.

🔍 Investigations

• 🩸 U&E: renal function. ALP ↑ with bone mets.
• 📊 FBC: anaemia or leucoerythroblastic picture.
• 📡 mpMRI now first-line before biopsy.
• 🧪 TRUS-guided biopsy if PSA >4 ng/mL.
• 🦴 Bone scan if PSA >20 ng/mL or bone pain.
• 🧬 Gleason score = grade/aggressiveness.

📊 Risk Stratification (Localised Disease)

Level	PSA	Gleason	Stage
Low	<10	6	T1–T2a
Intermediate	10–20	7	T2b
High	>20	8–10	≥T2c

🛠️ Prostate Cancer Treatment (UK – NICE NG131, 2021)

📌 Initial Workup

• Risk stratify with D’Amico or NICE criteria.
• Assess Gleason, PSA, MRI staging ± bone scan.
• Histology mandatory before radical Rx.

🏥 Localised Disease (T1–T2, N0, M0)

Low-risk (≤Gleason 6, PSA <10)

• 👀 Active surveillance in stable cases.
• Radical prostatectomy or radiotherapy in young/fit men.

Intermediate-risk (Gleason 7 or PSA 10–20)

• Prostatectomy ± LN dissection OR EBRT ± 3–6 mo ADT.
• 💡 Brachytherapy in select patients.

High-risk (Gleason ≥8, PSA >20)

• EBRT + 2–3 yr ADT = gold standard.
• Surgery only in expert centres.

📍 Locally Advanced (T3–T4, N0, M0)

• EBRT + long-term ADT improves survival.
• Selected surgery in multimodal settings.

🌍 Metastatic Disease (M1)

Hormone-sensitive (mHSPC)

• First-line = ADT (LHRH agonist/antagonist).
• + Docetaxel (high-volume) or novel oral (abiraterone, enzalutamide).

Castration-resistant (mCRPC)

• Continue ADT + abiraterone/enzalutamide.
• + Docetaxel or cabazitaxel if progression.
• 🦴 Radium-223 for bone-only mets with pain.
• 🧬 Olaparib for BRCA/HRR mutation-positive cancers.

🤝 Supportive & Palliative Care

• Bone protection: zoledronic acid or denosumab.
• Manage ADT effects: osteoporosis, metabolic syndrome, fatigue.
• 💊 Palliative radiotherapy for bone pain.

🇬🇧 UK-specific Notes

• Follow NICE NG131 (2021).
• MDT discussion mandatory.
• Lifelong PSA follow-up post-treatment.
• ⚖️ Frailty, comorbidities & QoL central to decisions in older patients.

Case 1 – Low-risk, suitable for active surveillance

62-year-old with LUTS and PSA 6.1 µg/L on primary care testing → 2WW referral; DRE benign, MRI PIRADS-3 apex lesion; targeted + systematic biopsies show Gleason 3+3=6 (Grade Group 1) in 2/12 cores, cT1c, PSA density 0.12. MDT counsels active surveillance per NICE: PSA every 3–6 months, repeat MRI at 12 months (earlier if PSA kinetics concerning), re-biopsy if radiological/PSA progression; optimise LUTS, lifestyle, and discuss triggers for definitive therapy.

Case 2 – Unfavourable intermediate risk, radical treatment

68-year-old with new erectile difficulties; PSA 12.8 µg/L, DRE: firm right hemi-gland; mpMRI PIRADS-5 right peripheral zone with possible extracapsular contact; targeted biopsy: Gleason 4+3=7 (Grade Group 3) in multiple cores, cT2b, CT/bone scan negative. MDT offers radical prostatectomy vs external beam radiotherapy + short-course ADT (4–6 months); patient chooses radiotherapy for nerve-sparing avoidance—plan: image-guided hypofractionation with androgen deprivation, then PSA nadir monitoring and management of GU/GI toxicities.

Case 3 – De novo metastatic, systemic therapy

74-year-old presents with back pain and weight loss; PSA 186 µg/L, DRE: hard, irregular prostate; staging shows multiple bone mets and pelvic nodes (M1b). Start androgen deprivation therapy plus treatment intensification (e.g., abiraterone or docetaxel per fitness/IMDC-style risk), early bone support (vitamin D/calcium; consider denosumab/zoledronate if castration-resistant), and analgesic/radiotherapy for painful sites. Discuss local prostate radiotherapy if low metastatic burden per STAMPEDE-aligned practice; monitor PSA, testosterone, symptoms, and metabolic/cardiovascular risks in primary–oncology shared care.