Update on Androgen Deprivation Therapy in Advanced Prostate Cancer
Androgen deprivation therapy (ADT) remains a foundation of treatment for advanced prostate cancer, but its role has changed substantially. For many men, testosterone suppression is now combined with a modern androgen-receptor pathway inhibitor or chemotherapy rather than used alone. This treatment evolution has improved disease control while making treatment selection more individualised.
Advanced disease may include biochemical recurrence after local treatment, cancer in regional lymph nodes, metastatic hormone-sensitive prostate cancer, or castration-resistant prostate cancer. The distinction matters because disease volume, symptoms, prior radiotherapy or surgery, comorbidities and genomic findings can all influence the next step.
For Australian patients, decisions also sit within the practical realities of the Therapeutic Goods Administration, Pharmaceutical Benefits Scheme (PBS), public hospital access and private prescribing. A treatment that is clinically appropriate still needs to be feasible, affordable and safely monitored over time.
How androgen deprivation works
Most prostate cancers use androgen receptor signalling to grow. ADT reduces this stimulation through luteinising hormone-releasing hormone agonists or antagonists, which lower testicular testosterone production. Surgical orchiectomy is less frequently selected, although it remains an effective permanent option in particular circumstances.
Medical ADT may be given by injections at intervals ranging from monthly to six-monthly, depending on the medicine. Oral androgen-receptor inhibitors, including abiraterone, enzalutamide, apalutamide and darolutamide, block androgen signalling through different mechanisms. Abiraterone also reduces androgen production outside the testes and must be paired with corticosteroid treatment.
ADT can improve cancer control, but it also affects normal physiology. Hot flushes, reduced libido, erectile dysfunction, fatigue, loss of muscle mass, weight gain, insulin resistance, mood changes and reduced bone mineral density are recognised consequences. Men who already have urinary symptoms should receive an integrated assessment; practical background on symptom assessment appears in this guide to lower urinary tract symptoms.
Intensifying treatment in hormone-sensitive disease
For metastatic hormone-sensitive prostate cancer, ADT alone is generally no longer the preferred strategy for men who can tolerate combination treatment. Adding an androgen-receptor pathway inhibitor improves radiographic progression-free survival and, in many groups, overall survival. Docetaxel remains an option, particularly for fit men with high-volume or aggressive metastatic disease.
Triplet therapy with ADT, docetaxel and darolutamide or abiraterone has become relevant for selected patients with newly diagnosed metastatic disease. The choice depends on fitness, disease burden, liver and cardiovascular health, drug interactions, previous treatment and the patient’s priorities. Men with limited metastatic recurrence may also be considered for metastasis-directed radiotherapy in addition to systemic treatment.
Disease volume is useful but should not replace clinical judgement. High-volume disease often involves visceral metastases or extensive bone involvement, while low-volume disease may be confined to a small number of sites. Symptoms such as spinal pain, weakness, urinary obstruction or impending fracture require urgent assessment rather than routine treatment escalation.
Selecting and monitoring modern regimens
The expected benefits and risks of commonly used approaches can be compared before treatment begins. This supports shared decision-making and helps clinicians explain why a regimen may be favoured for one patient but avoided in another.
| Treatment approach | Potential strengths | Important cautions and monitoring |
|---|---|---|
| ADT alone | Simple administration; useful when frailty or comorbidity limits combination therapy | Inferior cancer control for many fit men with metastatic hormone-sensitive disease; monitor testosterone, PSA, bone and metabolic health |
| ADT plus abiraterone | Strong disease-control evidence; oral treatment | Hypertension, low potassium, fluid retention, liver toxicity and steroid-related effects; check blood pressure, electrolytes and liver function |
| ADT plus enzalutamide | Effective oral androgen-receptor inhibition; no routine steroid requirement | Fatigue, falls, hypertension, seizures in predisposed patients and drug interactions |
| ADT plus apalutamide | Effective systemic intensification for appropriate hormone-sensitive disease | Rash, hypothyroidism, falls, fractures and cardiovascular risk require attention |
| ADT plus darolutamide | Lower central nervous system penetration may reduce some fatigue and cognitive effects; useful in selected combinations | Cost, access, drug interactions and suitability for combination chemotherapy still need review |
| ADT plus docetaxel | Finite chemotherapy course; useful for fit patients with aggressive metastatic disease | Neutropenia, infection, neuropathy, nail changes and fatigue; requires oncology support |
Monitoring should include prostate-specific antigen (PSA), testosterone, renal and liver function where relevant, blood pressure, weight, glucose or HbA1c, lipids and symptoms. A falling PSA is reassuring but does not prove complete disease control. Testosterone should be checked when PSA rises or progression is suspected, because inadequate castration levels can mimic treatment resistance.
Imaging is guided by symptoms, PSA kinetics and the clinical setting. Conventional CT and bone scans remain widely used, while prostate-specific membrane antigen positron emission tomography can detect disease at lower burdens in suitable patients. Access to PSMA-PET varies between Australian metropolitan and regional services, and Medicare eligibility or local referral pathways may affect timing.
Recognising castration-resistant progression
Castration-resistant prostate cancer is diagnosed when the cancer progresses despite castrate testosterone levels. Progression may be biochemical, radiographic or clinical. A rising PSA should prompt confirmation, medication review and testosterone measurement before assuming that the current treatment has failed.
Treatment after progression depends heavily on what the patient has already received. Options can include switching or adding systemic therapies, chemotherapy, radioligand therapy, PARP inhibition for selected homologous recombination repair mutations, or bone-targeted treatment. Sequential use of similar androgen-receptor inhibitors often produces limited benefit because cross-resistance is common.
Genomic testing can identify inherited or tumour-acquired alterations relevant to targeted treatment and family counselling. Testing practices continue to evolve, and referral to a uro-oncology or medical oncology service can help coordinate tissue, blood-based and germline testing. The journal’s editorial information provides access to the broader publication context in which emerging evidence in urology is reviewed.
Reducing harm during long-term ADT
Bone health deserves attention from the first injection, particularly in men with osteopenia, previous fractures, long treatment exposure or metastatic bone disease. Baseline fracture-risk assessment and bone mineral density testing can guide calcium and vitamin D advice, resistance exercise and the use of antiresorptive medication. Dental review is sensible before some bone-targeted treatments because of the small risk of osteonecrosis of the jaw.
Aerobic activity combined with resistance training can help preserve strength, balance and insulin sensitivity. Australian men may find walking groups, local council exercise programs or supervised physiotherapy useful, including in areas where gym access is limited. Smoking cessation, moderation of alcohol and a diet that supports healthy weight are relevant because cardiovascular and metabolic disease can influence both life expectancy and treatment tolerance.
Cardiovascular risk should be assessed before treatment intensification. Men with diabetes, established coronary disease, arrhythmia or uncontrolled hypertension may need coordination between a general practitioner, cardiologist and cancer team. Fatigue, depression, sleep disturbance and sexual health should be raised directly rather than treated as unavoidable side effects.
Kidney stones and reduced renal reserve can complicate hydration advice, imaging and medication choices. Clinicians managing these issues can draw on current information about medical management of nephrolithiasis, while adapting recommendations to the patient’s cancer treatment and laboratory results.
Applying evidence in Australian practice
Access is shaped by geography. Men living in Sydney, Melbourne, Brisbane, Perth or Adelaide may have several urology and oncology services nearby, while patients in regional and remote communities may travel long distances for injections, imaging or chemotherapy. Telehealth can support follow-up, but physical examinations, blood tests and some treatments still require local or metropolitan appointments.
The PBS is central to the Australian market for many cancer medicines, although listing criteria, authority requirements and indications can change. Private access may offer additional flexibility, but out-of-pocket costs can be substantial. The TGA regulates medicine approval, while state and territory health systems organise much of public hospital delivery; these are separate processes from PBS subsidy and should be explained clearly.
Medication reconciliation is particularly important when an oral androgen-receptor inhibitor is prescribed. Common medicines for diabetes, epilepsy, anticoagulation, hypertension and reflux can affect safety or drug levels. A written plan shared with the GP, community pharmacist and treating team can reduce missed doses and identify adverse effects early.
Useful priorities for clinical discussions include:
- Confirm the disease state, metastatic burden, symptoms and testosterone level before changing therapy.
- Match treatment intensity to fitness, cardiovascular risk, frailty, comorbidities and personal goals.
- Establish PSA, testosterone, blood pressure, metabolic, liver and bone-health monitoring at baseline.
- Ask about PBS eligibility, authority requirements, travel, injection timing and likely out-of-pocket costs.
- Include exercise, sexual health, mood, fracture prevention and palliative care support from the beginning.
A contemporary approach to advanced prostate cancer combines effective cancer control with careful survivorship planning. Patients and clinicians should review PSA and testosterone trends, imaging, side effects and personal priorities at regular intervals rather than relying on a single result. Australian urology and oncology teams can use multidisciplinary care, local pathology and telehealth links to make long-term ADT safer and more responsive to individual needs.