Combined chemohormonalradiation treatment of highand very-high-risk non-metastatic prostate cancer

Introduction. Treatment of highand very-high-risk prostate cancer appears to be extremely difficult. External beam radiation therapy combined with long-term androgen deprivation therapy (ADT) plays the main role, though low treatment effectiveness compared to one of intermediateand low-risk groups pushes towards finding new treatment options and modalities.

Objective: to enlighten data from modern publications and reviews concerning combined treatment uncluding (or not) chemotherapy and different types of radiation therapy.

Risk stratification. Several organizations (NCCN, NICE, ESMO, AUA, EAU and others) offer risk stratification systems. The NCCN system includes the very-high-risk group (Т3b–T4). Nowadays high-risk is set (EAU) when stages ≥ T2c or prostatic specific antigen > 20 ng/ml or Gleason score 8–10 appear.

External beam radiation therapy. Recommended dose is ≥ 74 Gy not depending on risk group. Low overall 10-years survival rate makes searching for new effective treatments inevitable.

ADT. Long-term regimens (2–3 years) of ADT in high-risk prostate cancer is undoubtable and neccecary. Biochemical progression-free survival can be achieved by using luteinizing hormone-releasing hormone antagonists in long-term regimens.

Brachytherapy. Brachytherapy alone and its combination with external beam radiation therapy show high effectiveness concerning progressionfree survival. In high-risk group survival rates are significantly lower. Improvement can be achieved by using adjuvant long-term ADT and other systemic therapy. Nowadays the results of such clinical trials are not available.

Chemotherapy. Chemotherapy as part of combination treatment of non-metastatic hormonal-sensitive high-risk prostate cancer is proved to be effective (increasing progression-free and overall survival), but still rarely used treatment option.

Conclusion. Reviews, meta-analyses and phase III clinical trials results show improvement of progression-free survival (and some – overall survival) when using a multimodal approach with chemotherapy. Combination treatment of taxane-base chemotherapy, luteinizing hormonereleasing hormone antagonists as ADT and brachytherapy alone or with external beam radiation therapy seems to be extremely perspective and needing further investigation.