Lucan · Conditions

Prostate cancer

Australian guidance: Cancer Council Australia / PCFA Clinical Guidelines + RACGP PSA position

1. Definition and epidemiology

Prostate cancer is a malignant epithelial neoplasm arising from the glandular cells of the prostate, most commonly from the peripheral zone. It is the most commonly diagnosed cancer in Australian men and the second most common cause of cancer-related death in males in Australia. Incidence rises steeply after the age of 50, and the majority of clinically significant disease is detected in men aged 60 to 79 years.

2. Pathophysiology

The vast majority of prostate cancers are acinar adenocarcinomas arising from secretory luminal cells. Carcinogenesis involves the progressive accumulation of genetic and epigenetic alterations: loss of the tumour suppressor PTEN, amplification of the androgen receptor gene, and fusion of the TMPRSS2 promoter with the ERG transcription factor oncogene are among the most characterised molecular events. Androgens, primarily dihydrotestosterone acting via the androgen receptor, drive proliferation of both normal and malignant prostate epithelium. This androgen dependence underpins the rationale for androgen deprivation therapy. Histologically, tumour glands lose their normal two-cell layer architecture, lack basal cells, and display prominent nucleoli. The Gleason grading system assesses architectural pattern from grade 3 (well-formed discrete glands) through grade 5 (solid sheets or single infiltrating cells), and the summed Gleason score from two representative areas predicts prognosis. Grade group 1 (Gleason 3+3=6) carries low malignant potential, while grade groups 4 to 5 (Gleason 8 to 10) are associated with rapid progression and metastasis. Metastatic spread follows lymphatic drainage to pelvic nodes and haematogenous dissemination, with bone being the predominant distant site, typically producing osteoblastic lesions visible on bone scan or prostate-specific membrane antigen (PSMA) PET/CT imaging.

3. Clinical presentation and diagnostic criteria

Most patients diagnosed in Australia are asymptomatic at the time of detection, identified after a prostate-specific antigen (PSA) test arranged through their general practitioner. When locally advanced disease is present, patients may report obstructive urinary symptoms (weak stream, hesitancy, incomplete emptying) or irritative symptoms (frequency, urgency, dysuria), as well as haematuria or haematospermia. Metastatic disease at presentation, while less common, may manifest as back or bone pain, leg oedema from lymphatic obstruction, weight loss, fatigue, or neurological symptoms including weak or numb lower limbs due to spinal cord or cauda equina compression. On digital rectal examination (DRE), a hard, nodular, or asymmetric prostate raises suspicion. Diagnosis requires histological confirmation; a PSA result alone is insufficient to initiate biopsy without DRE assessment and clinical context.

4. Investigations and AU-specific cutoffs

Initial investigations include serum total PSA, measurement of the free-to-total PSA ratio, and midstream urine to exclude prostatitis as a confounding cause of PSA elevation. A rising PSA, even within the age-adjusted normal range, carries clinical significance. Urgent specialist referral within 4 weeks is warranted for symptomatic patients, those with a PSA greater than or equal to 10 ng/mL on DRE, or a PSA above 50 ng/mL suggesting likely metastatic disease. Asymptomatic patients with persistently abnormal results or a single PSA reading at or above 10 ng/mL should be seen by a specialist within 4 weeks; asymptomatic patients with PSA below 10 ng/mL within 12 weeks. For staging, DRE assesses T-stage; CT abdomen and pelvis with bone scan provides standard staging; PSMA PET/CT has superior accuracy over conventional imaging for high-risk prostate cancers and is now preferred for assessing nodal or distant metastatic disease. Prostate biopsy under transrectal ultrasound or MRI fusion guidance provides histological confirmation. Multiparametric MRI before biopsy is recommended in eligible patients to guide targeted core sampling. PSA testing protocols per Cancer Council Australia / PCFA guidelines recommend PSA testing every 2 years for men aged 50 to 69 at average risk who elect testing after an informed discussion of benefits and harms; testing at age 40 to 69 every 2 years for high-risk men (family history of prostate cancer, BRCA2 mutation carriers); and no testing in men with a life expectancy below 7 years.

5. Management

Management is determined by risk stratification using Gleason grade group, clinical T-stage, and PSA level, in conjunction with life expectancy and patient preference, and should be discussed by a multidisciplinary team prior to commencement.

For low-risk localised disease (grade group 1, PSA below 10 ng/mL, clinical stage T1c to T2a), active surveillance is the preferred approach for most men, entailing close monitoring with serial PSA, DRE, and periodic repeat biopsy or MRI, allowing intervention to be deferred until signs of progression emerge. Watchful waiting is appropriate for men with other health conditions unlikely to live beyond 7 years, with treatment limited to symptom management if disease progresses.

For intermediate and high-risk localised or locally advanced disease, curative intent treatment options include radical prostatectomy or radiation therapy (external beam radiation and/or brachytherapy). Men considering curative treatment should obtain opinions from both a urologist and a radiation oncologist before deciding. Treatment should begin within 3 months of diagnosis for asymptomatic patients, or within 4 weeks if significant local symptoms are present.

For metastatic disease, androgen deprivation therapy (ADT) is the standard systemic treatment. The timing of initiating ADT requires balancing disease-related harms against treatment side effects. Additional systemic options for metastatic disease include cytotoxic chemotherapy (docetaxel), novel androgen receptor signalling inhibitors, bisphosphonates, and RANK ligand inhibitors. Early referral to palliative care is recommended based on need, not prognosis.

6. Pharmacology and AU PBS notes

Androgen deprivation therapy is achieved by surgical castration (bilateral orchidectomy) or medical castration using luteinising hormone-releasing hormone (LHRH) agonists or antagonists. PBS-listed LHRH agonists include leuprorelin (Lucrin, Eligard) and goserelin (Zoladex). LHRH antagonists include degarelix (Firmagon), which avoids the testosterone flare seen with agonists and is preferred where rapid castration is needed. Novel androgen receptor pathway inhibitors listed on the PBS for castration-resistant or metastatic hormone-sensitive prostate cancer include enzalutamide (Xtandi, PBS Restricted Benefit for metastatic castration-resistant prostate cancer) and abiraterone acetate (Zytiga, PBS Authority Required for metastatic castration-resistant disease when used with prednisone). Docetaxel (Taxotere and generics) is PBS-listed for metastatic prostate cancer. Bone-targeted agents include zoledronic acid (Zometa) for bone metastases and denosumab (Xgeva, RANK ligand inhibitor) for prevention of skeletal-related events; both require calcium and vitamin D supplementation. 5-alpha reductase inhibitors (finasteride, dutasteride) are not PBS-listed for cancer treatment but are used for lower urinary tract symptoms in the context of benign prostatic hyperplasia.

7. Complications and monitoring

Complications of active treatment include urinary incontinence and erectile dysfunction following radical prostatectomy, and bowel toxicity, urinary irritation, and sexual dysfunction following radiation therapy. ADT produces a predictable constellation of adverse effects: hot flushes, loss of libido, erectile dysfunction, fatigue, osteoporosis, metabolic syndrome, and cardiovascular risk; bone density monitoring with DEXA scanning is recommended for men on long-term ADT, and calcium and vitamin D supplementation should be offered. PSA nadir following definitive treatment is an important prognostic marker; biochemical recurrence is defined as a confirmed PSA rise above 0.2 ng/mL after radical prostatectomy or a PSA rise of 2 ng/mL above the post-radiotherapy nadir. Post-treatment surveillance involves regular PSA testing (every 3 to 6 months in the first 2 years, then annually if stable) with clinical review. Spinal cord compression is an oncological emergency in patients with vertebral metastases and requires urgent imaging and treatment with corticosteroids and definitive radiotherapy or surgery. Psychological distress, depression, and anxiety are common throughout the prostate cancer care journey and supportive care needs should be assessed at every step of the pathway.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.