What is the recommended management for locally advanced prostate cancer (Ca prostate)?

Management of Locally Advanced Prostate Cancer

For patients with locally advanced prostate cancer, the recommended management is a combination of external beam radiotherapy plus androgen deprivation therapy (ADT) for 24-36 months, as this approach has demonstrated significant improvements in overall survival and disease-specific mortality compared to single modality treatments. 1

Definition and Risk Stratification

Locally advanced prostate cancer typically refers to:

• T3-T4 disease (extension beyond the prostate capsule)
• May include node-positive (N1) disease without distant metastases
• Often associated with higher PSA levels and/or Gleason scores 1

Standard Treatment Approaches

Radiotherapy + Androgen Deprivation Therapy

This combination represents the gold standard approach for locally advanced disease:

• External beam radiotherapy (EBRT) combined with 24-36 months of ADT is strongly recommended for high-risk locally advanced prostate cancer 1
• The SPCG-7 trial demonstrated that adding radiotherapy to ADT significantly improved cause-specific mortality (11.9% vs 23.9%) and overall mortality (29.6% vs 39.4%) compared to ADT alone 1
• Neoadjuvant ADT for 3-6 months before and during radiotherapy is recommended 1
• For high-risk disease, adjuvant ADT should be continued for 2-3 years after radiotherapy completion 1

Surgical Approaches

While radiotherapy plus ADT is the primary approach, surgery may be considered in select cases:

• Radical prostatectomy may be an option for some patients with locally advanced disease 1
• Pelvic lymph node dissection (PLND) is recommended when performing radical prostatectomy for unfavorable intermediate or high-risk disease 1
• Patients should be counseled about potential adjuvant radiotherapy if adverse pathological features are found at prostatectomy 1
• Older patients experience higher rates of permanent erectile dysfunction and urinary incontinence after prostatectomy 1

Novel Hormonal Agents

Recent evidence supports enhanced hormonal therapy options:

• ADT plus abiraterone and prednisolone should be considered for men with locally advanced nonmetastatic prostate cancer rather than ADT alone 1
• This combination has demonstrated improved failure-free survival in the STAMPEDE trial 1
• In resource-constrained settings, combined androgen blockade using ADT plus a first-generation antiandrogen (flutamide, nilutamide, or bicalutamide) may be offered 1

Treatment Selection Algorithm

1. First-line approach: EBRT + long-term ADT (24-36 months) 1

   • Consider adding abiraterone and prednisolone to ADT if available 1

2. Alternative approaches (based on individual factors):

   • Radical prostatectomy with PLND for select patients, with consideration of adjuvant radiotherapy 1
   • ADT alone for patients who are not candidates for or decline radiotherapy 1

3. Factors influencing treatment selection:

   • Patient age and comorbidities
   • Extent of local disease
   • Presence of nodal involvement
   • Patient preferences regarding side effect profiles 1

Important Considerations and Potential Pitfalls

• ADT-related side effects: Patients should be informed that ADT with radiation increases the likelihood and severity of sexual dysfunction and can cause other systemic side effects 1
• Timing of therapy: Early (immediate) ADT may be offered to men with locally advanced disease who are unwilling or unable to undergo radiotherapy 1
• Radiation side effects: Following radical radiotherapy, the incidence of severe late normal tissue damage should be less than 5% at 2 years 1
• Surgical complications: Less than 5% of patients should have incontinence severe enough at one year to require more than 2 pads a day 1
• Monitoring: Regular follow-up with PSA measurements and appropriate imaging is essential to assess treatment response 2

Emerging Approaches

• Intermittent androgen deprivation (IAD) may be offered to patients with locally advanced prostate cancer treated with hormonal therapy alone 1
• Several clinical trials are investigating the role of newer hormonal agents in the locally advanced setting 3, 4

By following this evidence-based approach to locally advanced prostate cancer management, clinicians can optimize patient outcomes while minimizing treatment-related morbidity.