Long-term Toxicity Outcomes After High-Dose Conformal Radiotherapy for Clinically Localized Prostate Cancer

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 10 de noviembre del 2006

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Presenter: A. Shippy
Presenter's Affiliation: Memorial Sloan-Kettering Cancer Center
Type of Session: Scientific

Background

  • Higher doses of radiotherapy have been shown in prospective randomized trials to correlate with improved clinical outcomes in prostate cancer patients
  • Toxicity has also been found to increase with increasing dose, though information on late toxicity is more difficult to find
  • This retrospective study sought to evaluate late toxicity outcomes for patients with clinically localized prostate cancer treated with high-dose external beam radiotherapy

Materials and Methods

  • Patients with clinically localized prostate cancer who were treated with conformal external beam radiotherapy between 1988 and 2000 at Memorial Sloan-Kettering Cancer Center were evaluated for long-term toxicity outcomes
  • Toxicity data were scored as per the Common Terminology Criteria for Adverse Events Version 3.0
  • Patients were treated with 3-D CT-guided radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT), to doses ranging from 64.8 - 81 Gy
  • Doses were prescribed to the isodose line that completely covered the planning target volume for patients receiving 70.2 Gy and 75.6 Gy, and to the isodose line that covered approximately 90-95% of the target volume for patients receiving 81 Gy

Results

  • 1,571 patients with cT1-3 prostate cancer treated with conformal external beam radiotherapy between 1988 and 2000 were studied
  • The median follow-up duration was 7 years (range 0-16)
  • The majority of patients had intermediate- or high-risk disease (42% of patients with intermediate-risk; 36% of patients with high-risk disease)
  • The following is a summary of radiation doses utilized:
    • 358 patients (23%) received <70.2 Gy
    • 472 patients (30%) received 75.6 Gy
    • 741 patients (47%) received 81 Gy
  • All patients receiving 75.6 Gy were treated with 3D-CRT and 90% of patients receiving 81 Gy were treated with IMRT
  • 678 patients (43%) received a short-term course of neoadjuvant and concurrent androgen ablation therapy
  • The overall incidence of GI toxicity at 10 years for all patients:
    • 74% with grade 0
    • 18% with grade 1
    • 7% with grade 2
    • 1% with grade 3
    • <1% with grade 4
  • There was a significant difference in the incidence of 10-year grade 2 GI toxicity based on radiation dose (6% with 70.2 Gy vs. 20% with 75.6 Gy vs. 4% with 81 Gy, p<0.001)
  • There was a significant difference in the incidence of 7-year grade 2 GI toxicity based on type of radiation received (12% with 3D-CRT vs. 2% with IMRT, p<0.001)
  • The overall incidence of grade 3 or higher GI toxicity at 10 years for all patients by dose:
    • 1% with <70.2 Gy
    • 2% with 75.6 Gy
    • 1% with 81 Gy
  • The overall incidence of GU toxicity at 10 years for all patients:
    • 65% with grade 0
    • 25% with grade 1
    • 7% with grade 2
    • 3% with grade 3
    • <1% with grade
  • There was a trend toward a statistically significant difference in the incidence of 10-year grade 2 GU toxicity based on radiation dose (10% with <70.2 Gy vs. 13% with 75.6 Gy vs. 10% with 81 Gy, p=0.07)
  • The overall incidence of grade 3 and higher GU toxicity at 10 years for all patients by dose:
    • 4% with <70.2 Gy
    • 2% with 75.6 Gy
    • 5% with 81 Gy
  • There were no significant differences in GI or GU toxicity among patients receiving short-term androgen ablation and radiotherapy vs. those patients receiving radiotherapy alone
  • Approximately 34% of patients who were potent prior to treatment maintained potency at 10 years, and the use of short-term androgen ablation therapy (p<0.001) and higher radiation doses (p<0.001) significantly increased the risk of erectile dysfunction

Author's Conclusions

  • High-dose conformal radiotherapy is well-tolerated on a long-term basis, and late grade 3 GI or GU toxicity is uncommon
  • IMRT is associated with a decreased risk of late GI toxicity compared to 3D-CRT, though this has not been the case with late GU toxicity
  • The majority of patients experience long-term erectile dysfunction, and this risk is increased with the use of androgen ablation therapy and higher radiation doses

Clinical/Scientific Implications

This retrospective report supports the notion that radiation dose escalation can be accomplished with acceptable toxicity in prostate cancer patients. IMRT appears to have impacted positively on rectal toxicity, though late urinary morbidity appears equivalent between patients treated with 3D-CRT and IMRT. This study is valuable in that it represents one of the few reports on late toxicity in prostate patients treated with IMRT.


News
Long-term adverse outcomes not more common than with standard-dose radiation

Mar 17, 2010 - Compared with standard-dose radiation, high-dose radiation treatments for localized prostate cancer are not associated with increased long-term treatment-related outcomes for urinary, bowel and sexual functions affecting quality of life, according to a study in the March 17 issue of the Journal of the American Medical Association.



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