Advanced Prostate Cancer Management
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Direct answer
Advanced prostate cancer — locally advanced non-metastatic, or metastatic at presentation — is managed around androgen deprivation therapy (ADT), delivered as bilateral subcapsular orchidectomy or medical castration with LHRH agonists such as leuprolide or antagonists such as degarelix. Hormone-naive metastatic disease in a fit man now adds androgen-receptor pathway inhibitors (abiraterone with prednisolone, or enzalutamide) or docetaxel chemotherapy to ADT, because trials show improved survival over ADT alone. When progression occurs despite castrate testosterone levels (under about 50 ng/dL), the disease is castration-resistant, and sequencing moves through abiraterone or enzalutamide, docetaxel and cabazitaxel, with radium-223 for symptomatic bone-predominant disease and supportive bone protection throughout.
What you must remember
- Castration levels: surgical orchidectomy works within about 12 hours and is permanent, cheap and adherence-proof — still highly relevant in Indian practice; LHRH agonists cause an initial testosterone flare needing 2-4 weeks of anti-androgen cover.
- Hormone-naive metastatic disease: ADT plus abiraterone-prednisolone or plus docetaxel (six cycles) improves overall survival in high-burden disease, per the landmark STAMPEDE and LATITUDE/CHAARTED analyses; ADT alone is no longer the ceiling.
- Locally advanced non-metastatic (T3-4 or node-positive): external-beam radiotherapy plus 18-36 months of ADT outperforms either alone; ADT alone is reserved for the unfit.
- Castration-resistant prostate cancer (CRPC): progression — rising PSA, new lesions or symptoms — despite castrate testosterone; continue ADT backbone while adding the next agent.
- Radium-223, an alpha-emitter, improves survival in symptomatic bone-only (no visceral) metastases; not combined with abiraterone-prednisolone outside trials.
- Bone health: zoledronic acid or denosumab reduces skeletal-related events in bone metastases; ADT itself accelerates osteoporosis, so calcium, vitamin D, baseline bone density and exercise counselling are part of care.
- BRCA2 and other homologous-recombination gene mutations matter: germline testing is advised in metastatic disease, and olaparib (a PARP inhibitor) is an option after progression in mutation carriers.
- Side-effect counselling for ADT: hot flushes, loss of libido, gynaecomastia, metabolic syndrome and osteoporosis.
Where students slip
The classic confusion is "castration-resistant means stop ADT" — wrong; testosterone suppression is maintained while the next-line androgen or chemotherapy agent is layered on, because any testosterone rebound can flare disease. The second is the flare phenomenon: starting an LHRH agonist alone in a man with impending cord compression or severe obstructive symptoms can worsen him within days; cover with an anti-androgen or use an antagonist (degarelix), which suppresses without a flare. Third, "ADT failure" dates: responses to first-line ADT typically last a few years, and the definition of CRPC is progression at castrate levels — not a particular PSA number. Fourth, exam vintage matters: papers written before 2015 expect "ADT alone" for metastatic disease; current teaching and guidelines expect combination therapy in fit men with high-burden disease, and answers should reflect that. Finally, do not forget that the orchidectomy — the oldest, surest and cheapest castration — remains a completely respectable answer in a resource-constrained setting or a non-adherent patient.
Frequently asked questions
What defines castration-resistant prostate cancer?
Progression — rising PSA, new radiographic lesions or worsening symptoms — despite surgical or medical castration with testosterone at castrate levels (commonly under 50 ng/dL or 1.7 nmol/L); ADT is continued alongside subsequent therapy.
Which agents improve survival when added to ADT in metastatic hormone-naive disease?
Abiraterone plus prednisolone, enzalutamide, and docetaxel chemotherapy in fit men with high-burden disease, each supported by randomised evidence such as STAMPEDE, LATITUDE and CHAARTED.
When is bilateral orchidectomy preferred over medical castration?
When adherence, cost or immediate, irreversible castration matters — it is fast, cheap and definitive; complications include hot flushes and psychological impact, so consent must be explicit.
What is the role of radium-223?
An intravenous alpha-emitting bone-seeking isotope that improves survival and delays skeletal events in symptomatic, bone-predominant metastases without visceral disease; it is not combined with abiraterone outside trials.
Why does ADT threaten bone health?
Suppression of testosterone accelerates osteoporosis and fracture risk, and metastases add skeletal events; management includes calcium and vitamin D, bone density assessment, resistance exercise, and bisphosphonates or denosumab where indicated.