Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation

Brachytherapy. 2020 May-Jun;19(3):275-281. doi: 10.1016/j.brachy.2020.01.008. Epub 2020 Mar 23.

Abstract

Purpose: Men with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT).

Methods and materials: Three hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan-Meier method with associations determined by log rank and Cox regression.

Results: Ten-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001).

Conclusions: Survival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.

Keywords: Brachytherapy; High grade; Prostate cancer; Survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brachytherapy*
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Kallikreins / blood*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Palladium / therapeutic use
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radioisotopes / therapeutic use
  • Radiotherapy Dosage
  • Radiotherapy, Conformal*
  • Survival Rate

Substances

  • Iodine Radioisotopes
  • Radioisotopes
  • Palladium
  • Palladium-103
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • Iodine-125