Hypofractionated external beam radiotherapy to boost the prostate with ≥85 Gy/equivalent dose for patients with localised disease at high risk of lymph node involvement: feasibility, tolerance and outcome

Clin Oncol (R Coll Radiol). 2014 Jun;26(6):316-22. doi: 10.1016/j.clon.2014.02.014. Epub 2014 Mar 22.

Abstract

Aims: To evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique.

Materials and methods: Between 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0-50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system.

Results: All patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049).

Conclusions: The use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.

Keywords: HDR; IMRT; WPRT; hypofractionation; prostate cancer; toxicity.

MeSH terms

  • Adult
  • Aged
  • Androgen Antagonists / administration & dosage
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Combined Modality Therapy
  • Disease-Free Survival
  • Dose Fractionation, Radiation*
  • Feasibility Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / prevention & control*
  • Lymphatic Metastasis / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radiation Injuries / epidemiology
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal