What is the standard treatment for prostate cancer recurrence?

Standard Treatment for Prostate Cancer Recurrence

The standard treatment for prostate cancer recurrence is androgen deprivation therapy (ADT), which remains the mainstay of treatment for metastatic and recurrent prostate cancer, with bilateral orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists being the recommended initial treatments. 1

Initial Treatment Options for Recurrent Prostate Cancer

• Bilateral orchiectomy (surgical castration) or LHRH agonists are the recommended first-line treatments for recurrent prostate cancer 1
• Nonsteroidal antiandrogen (NSAA) monotherapy may be discussed as an alternative treatment option, but steroidal antiandrogen monotherapy should not be offered 1
• Combined androgen blockade (CAB), which involves adding an antiandrogen to medical or surgical castration, should be considered as it may provide improved overall survival, though with potentially increased adverse effects 1

Treatment Based on Type of Recurrence

For Local Intraprostatic Recurrence After Radiotherapy

• Local salvage with reirradiation is usually appropriate for isolated intraprostatic recurrence 1
• Alternative local salvage options include cryotherapy or high-intensity focused ultrasound (HIFU), though these may be less effective than reirradiation 1
• Focal salvage should be pursued when confidence in focal recurrence can be confirmed via multiple radiographic and tissue sampling modalities 1

For Biochemical Recurrence (Rising PSA)

• For patients with biochemical recurrence and positive PSMA PET findings but negative conventional imaging, novel hormonal agents such as enzalutamide are recommended 2, 3
• Enzalutamide is FDA-approved for castration-resistant prostate cancer and has shown efficacy in delaying metastasis in patients with rising PSA 3
• Continuing ADT concurrently with enzalutamide is recommended for castration-resistant prostate cancer 2, 3

For Metastatic Recurrence

• Standard hormonal therapy (ADT) is recommended for stage N1/M0 (nodal metastasis) and M1 (distant metastasis) disease 1
• For metastatic castration-sensitive prostate cancer, the addition of androgen receptor pathway inhibitors (e.g., darolutamide, abiraterone) to ADT improves survival 4
• Chemotherapy (docetaxel) may be considered for patients with more extensive metastatic disease 4

Timing of Androgen Deprivation Therapy

• The optimal timing of ADT initiation remains controversial, with no clear overall survival advantage for immediate versus deferred therapy 1
• Immediate ADT results in a moderate decrease (17%) in relative risk for prostate cancer-specific mortality but a moderate increase (15%) in relative risk for non-prostate cancer-specific mortality 1
• For patients with adverse prognostic factors (short PSA doubling time, high Gleason score), earlier intervention may be beneficial 1, 2
• For patients electing to wait until symptoms develop before starting ADT, regular monitoring visits are essential 1

Intermittent versus Continuous ADT

• Currently, data are insufficient to support the routine use of intermittent androgen blockade outside clinical trials 1
• Smaller non-randomized studies have shown that patients spent 35% to 55% of each cycle off therapy when treated intermittently, and after the first cycle, greater than 90% responded to reinstitution of ADT 1

Important Considerations and Monitoring

• PSA measurements should be performed every 3-4 weeks initially to assess response to therapy 2
• Regular imaging follow-up with CT scans and bone scintigraphy should be considered to assess response 2
• Avoid relying solely on PSA for monitoring response, as radiographic progression can occur without PSA elevation in up to 24.5% of patients on novel hormonal agents 2
• Monitor for potential adverse effects of hormonal therapies, including fatigue, hot flashes, and cardiovascular complications 2, 3

Treatment for High-Risk Patients

• For high-risk patients (T3a or Gleason score 8-10 or PSA > 20 ng/ml), androgen deprivation therapy (at least 2 years) combined with 3-dimensional radiation therapy is recommended 1
• For very high-risk patients (T3b-T4), the same combination therapy is recommended 1
• Neoadjuvant or adjuvant hormone therapy should be included in the protocol for high-risk patients with localized prostatic tumors 1