Hormonal Therapy and Radiation Therapy in Prostate Cancer: 5-Year Outcomes From a Trial Evaluating Combined Androgen Blockade With 5-Alpha Reductase Inhibitors as an Alternative to Gonadotropin Releasing Hormone Agonists

Clin Genitourin Cancer. 2024 Aug;22(4):102103. doi: 10.1016/j.clgc.2024.102103. Epub 2024 Apr 24.

Abstract

Background: We previously reported that for men undergoing combined androgen deprivation therapy (ADT) and radiation therapy (RT) for prostate cancer, substitution of LHRH-agonists with 5-α- reductase inhibitors (5-ARIs) led to improved preservation of 6-month hormonal quality of life (hQOL). With longer term follow-up, we evaluated disease control.

Methods: In this non-randomized trial, men with unfavorable intermediate or high-risk prostate cancer, aged ≥70 years or with Charlson Comorbidity Index ≥2, were treated with RT (78-79.2 Gy in 39-44 fractions) and either oral ADT (oADT; 5-ARI with antiandrogen) or standard of care ADT (SOC; leuprolide with antiandrogen) for up to 28 months. The primary endpoint was EPIC hQOL; secondary endpoints included biochemical control and survival as well as changes in cholesterol and hemoglobin levels.

Results: Between 2011 and 2018, 70 men were enrolled (40 in oADT; 30 in SOC). Median follow-up was 65 months [IQR 36-94]. Five-year freedom from biochemical failure for oADT and SOC was 89% versus 86%, disease free survival was 62% versus 69%, cancer-specific survival was 100% versus 96%, and overall survival was 70% versus 81% (all P>.1). Testosterone (2 mo through 3 yr) and hemoglobin levels (2 mo through 2 yr) were higher, and cholesterol levels (1 yr) were lower in the oADT groups (all P < .05).

Conclusions: In this non-randomized study, men treated with combined RT and oADT had better preservation of hQOL and comparable 5-year disease outcomes to men treated with SOC. Eugonadal testosterone with this approach may yield measurable benefits in cholesterol and hemoglobin levels.

Keywords: Androgen deprivation therapy (ADT); Biochemical outcomes; Intermediate/high risk prostate cancer; Quality of life; Testosterone.

MeSH terms

  • 5-alpha Reductase Inhibitors* / administration & dosage
  • 5-alpha Reductase Inhibitors* / therapeutic use
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists* / administration & dosage
  • Androgen Antagonists* / therapeutic use
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Follow-Up Studies
  • Gonadotropin-Releasing Hormone* / agonists
  • Humans
  • Leuprolide / administration & dosage
  • Leuprolide / therapeutic use
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Prostatic Neoplasms* / therapy
  • Quality of Life*
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Gonadotropin-Releasing Hormone
  • 5-alpha Reductase Inhibitors
  • Leuprolide
  • Antineoplastic Agents, Hormonal