What are the medical and surgical management options for prostate cancer?

Medical and Surgical Management Options for Prostate Cancer

Treatment of prostate cancer should be based on cancer stage, grade, PSA level, and patient's life expectancy, with radical prostatectomy or external beam radiation therapy recommended for higher-risk patients, while active surveillance is appropriate for low-risk disease. 1

Risk Stratification and Initial Assessment

• Clinical tumor stage, Gleason score, and pretreatment PSA concentration are the primary prognostic factors for determining appropriate treatment strategy 1
• Additional prognostic factors include Gleason grades present, number of affected biopsies, extent of tumor tissue in core biopsies, and perineural invasion 1
• Partin tables can be used to evaluate the risk of extraprostatic spread and pelvic node invasion before treatment 1
• A 10-year metastasis-free survival is an acceptable criterion for evaluating treatment response for localized prostate cancer 1

Treatment Options for Localized Disease (T1-T2)

Active Surveillance/Watch and Wait Policy

• Appropriate for patients with low-risk disease (T1-T2a, Gleason <6, PSA <10 mg/L) 1
• Should be discussed as an option for patients with low-risk disease as no overall survival benefit has been demonstrated with active treatment 1
• Particularly suitable for patients with stage T1c or T2 prostate cancer with a life expectancy of less than 10 years 1
• Active surveillance has shown 99% disease-specific survival at 8 years for low-risk disease 1
• Despite low mortality risk in low-risk patients, about 94% of patients with localized prostate cancer choose treatment 1

Radical Prostatectomy

• Standard treatment for patients with stage T1a, T1b, T1c, or T2 prostate cancer with life expectancy >10 years who accept treatment-related complications 1
• Associated with urinary incontinence (49% vs 21%) and erectile dysfunction (80% vs 45%) compared to watchful waiting 1
• Can be considered for selected cases of stage T3 and pN1 cancers, but not recommended for pN1 high-grade tumors (Gleason score >7) 1
• Radical prostatectomy may be associated with lower risk of cancer recurrence and cancer-related death compared to watchful waiting based on one RCT 1
• The criterion for complete remission after radical prostatectomy is an undetectable PSA concentration (<0.1 mg/L) for at least 7 years 1

External Beam Radiation Therapy (EBRT)

• Should be delivered using conformal techniques to a minimum target dose of 70 Gy given in 2.0 Gy fractions or equivalent 1
• Conformal radiotherapy reduces late toxicity compared with conventional radiotherapy and should be used when giving high doses 1
• Dose escalation above 74 Gy benefits patients with intermediate prognosis receiving radiotherapy alone 1
• Patients with good prognosis (T1-T2a, PSA <10 mg/L, Gleason 2-6) have not shown benefit from dose escalation above 70-74 Gy 1
• Risk factors for complications include prior transurethral prostatic resections and higher radiation doses 1

Brachytherapy

• An option for low- and moderate-risk patients 1
• Retropubic brachytherapy should no longer be used 1
• Iridium is the standard isotope for temporary implant brachytherapy 1
• Can be delivered as low-dose rate or high-dose rate treatment 1
• In nonrandomized prospective series, brachytherapy with permanent implants shows similar long-term survival to radical prostatectomy with less urinary morbidity and erectile dysfunction 1

Treatment Options for Locally Advanced Disease (T3-T4)

Combined Modality Approaches

• External beam radiotherapy combined with hormone therapy is the standard treatment for locally advanced disease 1
• Hormone therapy (for at least 2 years) combined with 3D radiation therapy is recommended for high-risk patients (T3a or Gleason 8-10 or PSA >20 ng/mL) and very high-risk patients (T3b-T4) 1
• Neoadjuvant or adjuvant hormone therapy should be considered for patients with locally advanced (T3-4) disease receiving radical radiotherapy 1
• For stage T3 with life expectancy >5-10 years, dose escalation >70 Gy appears beneficial; if unavailable, combination with hormone therapy is recommended 1

Radical Prostatectomy for Advanced Disease

• Radical prostatectomy plus extended lymphadenectomy can be considered in highly selected cases of high-risk or locally advanced prostate cancer 1
• Should only be undertaken in stage T3 and pN1 cancers in the setting of a randomized clinical trial assessing efficacy alone or in combination with other treatments 1

Treatment Options for Metastatic Disease

Androgen Deprivation Therapy (ADT)

• Standard first-line treatment for metastatic hormone-naïve prostate cancer 2
• Administered through bilateral orchiectomy (surgical castration) or LHRH agonists (medical castration) 2, 3
• When starting LHRH agonist treatment, an antiandrogen should be given for 3-4 weeks to prevent testosterone flare 2, 4
• Continuous ADT is recommended over intermittent ADT for metastatic hormone-naïve prostate cancer 2
• Regular exercise should be recommended for men starting ADT as it reduces fatigue and improves quality of life 2

Chemotherapy and Advanced Treatment Options

• ADT plus docetaxel is recommended as first-line treatment for metastatic hormone-naïve disease in men fit enough for chemotherapy 2
• For castration-resistant prostate cancer (CRPC), options include:
  • Abiraterone or enzalutamide for asymptomatic/mildly symptomatic chemotherapy-naïve metastatic CRPC 2
  • Docetaxel for men with metastatic CRPC 2
  • Radium-223 for men with bone-predominant, symptomatic metastatic CRPC without visceral metastases 2

Management of Bone Metastases

• Single fraction of external beam radiotherapy is recommended for palliation of painful bone metastases 2
• Denosumab or zoledronic acid can be recommended for patients with bone metastases from CRPC at high risk for clinically significant skeletal-related events 2
• MRI of the spine to detect subclinical cord compression is recommended in men with CRPC with vertebral metastases 2

Monitoring and Follow-up

• Patients receiving ADT should be monitored with clinical assessment and PSA measurement 2
• Men on long-term ADT should be monitored for side effects including osteoporosis (using bone densitometry) and metabolic syndrome 2
• The criterion for progression after radical prostatectomy, external-beam radiotherapy, or brachytherapy is an increase in PSA concentration measured on three successive occasions at monthly intervals 1
• Following radical prostatectomy, patients should be monitored with a sensitive PSA assay, with salvage radiotherapy to the prostate bed given in the event of PSA failure 1

Important Considerations and Caveats

• Despite widespread PSA screening, about 90% of patients are diagnosed with localized prostate cancer, but treatment is associated with urinary, sexual, and bowel dysfunction 1
• Treatment enhances quality-adjusted survival of low-risk patients by only 1.2 months 1
• Hyperglycemia and increased risk of developing diabetes have been reported in men receiving GnRH agonists 4
• Increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported with GnRH agonists 4
• PSA is not always a reliable indicator of disease activity in patients with undifferentiated metastatic prostate cancer with neuroendocrine features 2