Advanced Prostate Cancer: How Treatment Is Chosen

"Advanced" prostate cancer covers two situations: a rising PSA after surgery or radiotherapy with no visible metastases (biochemical recurrence), and cancer that has spread to bones, lymph nodes or organs. Both are treatable for years, and treatment choice depends on how fast the disease is moving, where it is, what has been used before, and what the patient values. The 2020 joint AUA/ASTRO/SUO guideline organises decisions around these questions.

Rising PSA without visible spread

After prostatectomy or radiotherapy, a rising PSA almost always precedes visible metastasis, and the speed of the rise is the key prognostic marker — PSA doubling time under about ten to twelve months signals higher risk of metastasis. Before treatment, the guideline recommends confirming the rise, repeating PSA and clinical assessment, and imaging with modern techniques: PSMA PET, or conventional CT/bone scan plus MRI where PSMA is unavailable. For patients at high risk of metastasis, adding androgen deprivation to salvage radiotherapy improves outcomes; for many others, careful surveillance — reserving treatment until metastases appear — is a legitimate option that avoids years of hormonal side effects.

Metastatic hormone-sensitive disease

Androgen deprivation therapy (ADT) — medical or surgical castration — remains the backbone. Current standard is intensification: ADT combined with an androgen receptor pathway inhibitor such as abiraterone, enzalutamide or apalutamide, or with docetaxel chemotherapy for patients with high-volume disease. An important practical point from the guideline: when an anti-androgen such as bicalutamide or flutamide is combined with an LHRH agonist, testosterone flare must be blocked. For patients with low-volume metastatic disease, radiotherapy to the primary prostate in addition to ADT improves outcomes. ADT should be intermittent rather than continuous only in selected, carefully counselled patients.

Castration-resistant disease

When PSA or scans progress despite castrate testosterone levels, the disease is termed castration-resistant, and multiple options follow: continued androgen blockade with enzalutamide, abiraterone or apalutamide; docetaxel or cabazitaxel chemotherapy; radium-223 for symptomatic bone metastases without visceral disease; PARP inhibitors for patients with BRCA or homologous recombination repair gene alterations; and sipuleucel-T or pembrolizumab in specific biomarker-defined settings. Sequencing is chosen according to prior exposure, symptom burden and genomic results — which is why metastatic patients should have germline and, where possible, tumour genomic testing.

Protecting bones and quality of life

Bone metastases cause pain, fractures and spinal cord compression. Bone-protecting agents — denosumab or zoledronic acid — reduce skeletal complications and should be paired with calcium and vitamin D and dental review before starting, because osteonecrosis of the jaw, though uncommon, is a real risk. Pain management, radiotherapy for painful bone sites, and early involvement of palliative care alongside active treatment all improve quality of life.

Living with the treatment

ADT causes hot flushes, fatigue, loss of muscle and bone density, sexual changes, weight gain and metabolic effects. These are manageable: resistance exercise, calcium and vitamin D, bone density monitoring, cardiovascular risk management, and honest discussion about sexual and psychological effects. The guideline emphasises a multidisciplinary approach — urology, radiation oncology, medical oncology and supportive care — because the sequence of choices over years is what determines outcome.