What is the recommended treatment approach for patients with prostate cancer?

Treatment Approach for Prostate Cancer

Treatment for prostate cancer must be stratified by disease stage and risk category, with localized low-risk disease managed by active surveillance, intermediate-risk disease treated with radical prostatectomy or radiotherapy, high-risk localized disease requiring radiotherapy plus prolonged androgen deprivation therapy (ADT), and metastatic disease treated with ADT plus treatment intensification using androgen receptor pathway inhibitors. 1, 2

Localized Disease Management

Low-Risk Disease (PSA <10 ng/mL, Gleason ≤6, Stage T1-T2a)

• Active surveillance is the preferred approach for patients with low-risk localized prostate cancer, achieving 99% disease-specific survival at 8 years 1, 2
• Active surveillance involves serial PSA measurements, prostate biopsies, or MRI monitoring with treatment initiation only if Gleason score or tumor stage increases 3, 2
• Approximately one-third of patients with localized prostate cancer are appropriate candidates for active surveillance 3
• No benefit for active treatment over observation has been demonstrated in overall survival for low-risk disease 1

Intermediate-Risk Disease (PSA 10-20 ng/mL OR Gleason 7 OR Stage T2b)

• Radical prostatectomy and external beam radiotherapy are equally effective treatment options 1, 2
• High-dose rate brachytherapy is an alternative option for select intermediate-risk patients 1, 2
• For patients receiving radiotherapy, neoadjuvant LHRH agonist therapy for 4-6 months should be considered 1
• Pelvic MRI should ideally be performed for intermediate-risk patients treated with radical radiotherapy 1

High-Risk Disease (PSA >20 ng/mL OR Gleason 8-10 OR Stage ≥T2c)

• External beam radiotherapy combined with ADT for at least 2-3 years is the standard treatment 1, 2
• Neoadjuvant LHRH agonist therapy for 4-6 months is recommended before radiotherapy 1
• Adjuvant hormonal therapy for 2-3 years following radiotherapy significantly improves local control, reduces disease progression, and improves overall survival 1
• Radical prostatectomy plus extended lymphadenectomy can be considered only in highly selected cases 1
• External beam radiotherapy should deliver a minimum target dose of 70 Gy using conformal techniques 1

Post-Treatment Management

After Radical Prostatectomy

• PSA should be below detection level within 2 months after surgery 1
• Salvage radiotherapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) for biochemical recurrence, as delayed treatment reduces effectiveness 1, 2
• Adjuvant hormone therapy after radical prostatectomy is not routinely recommended 1
• Patients with positive surgical margins or extracapsular extension should be informed about pros and cons of adjuvant radiotherapy 1

After Radiotherapy

• Early ADT is not routinely recommended for biochemical relapse unless patients have symptomatic local disease progression, proven metastases, or PSA doubling time <3 months 1, 2
• Intermittent androgen deprivation is not inferior to continuous therapy and provides quality-of-life benefits 1

Metastatic Disease Management

Metastatic Castration-Sensitive Prostate Cancer

• ADT with treatment intensification is strongly recommended for all patients with metastatic castration-sensitive disease 1
• Medical castration using LHRH agonists or surgical castration (bilateral orchiectomy) forms the treatment backbone 4, 1
• An antiandrogen must be given for 3-4 weeks when starting LHRH agonist therapy to counteract testosterone flare 4, 1
• Adding androgen receptor pathway inhibitors (abiraterone or darolutamide) to ADT improves median overall survival from 36.5 months to 53.3 months (hazard ratio 0.66) 3
• For patients fit enough to receive chemotherapy, continuous ADT plus docetaxel is first-line treatment 2
• Combined androgen blockade with nonsteroidal antiandrogens may be offered to patients willing to accept increased toxicity for a small survival benefit 1

Castration-Resistant Prostate Cancer (CRPC)

• Androgen suppression must be continued even after progression to castration resistance 1, 4
• Patients should be considered for further hormone therapies (abiraterone or enzalutamide) if not previously used 1, 2
• Docetaxel using a 3-weekly schedule is recommended for symptomatic castration-resistant disease 1
• Cabazitaxel is more effective than mitoxantrone in patients previously treated with docetaxel 1
• Chemotherapy may be preferable in patients with poor initial hormone response or severe symptoms 1
• Sequential addition of secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and targeted therapies should follow a shared decision-making approach 1

Critical Treatment Considerations

Antiandrogen Therapy Specifics

• Bicalutamide 150 mg daily can be used as an alternative to LHRH agonists for patients who prefer its toxicity profile, though outcome data are limited 1
• Breast irradiation (8-15 Gy in 1-3 fractions) should be given 1-2 weeks before initiating antiandrogen therapy to prevent painful gynecomastia 1
• Gynecomastia and breast pain occur in up to 38-39% of patients receiving bicalutamide 5
• Close monitoring of PT/INR is required when bicalutamide is used with coumarin anticoagulants due to risk of excessive prolongation and serious bleeding 5

Monitoring and Follow-up

• Regular PSA assessments are essential for monitoring treatment response 1
• Blood glucose monitoring should be considered in patients receiving LHRH agonists due to reduced glucose tolerance 5
• Bone scintigraphy is not routinely recommended for low-risk disease but should be performed for high-risk disease or when PSA >10 mg/l 1

Common Pitfalls to Avoid

• Overtreatment of low-risk disease: Proper counseling about active surveillance as a safe option is essential to avoid unnecessary treatment-related morbidity 2
• Inadequate biopsy sampling: A minimum of 8-10 cores should be obtained under antibiotic cover with TRUS guidance 1, 2
• Ignoring life expectancy: Curative treatment offers minimal benefit when life expectancy is <10 years and should generally not be recommended 1, 2
• Delayed salvage radiotherapy: Effectiveness is maximized when PSA is <0.5 ng/mL after prostatectomy 2