Patient Reported Quality of Life in Prostate Cancer Patients Treated with 3D conformal, Intensity Modulated or Proton Beam Radiation Therapy

Reporter: Annemarie Fernandes, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 28, 2012

Presenter: Phillip Gray, MD
Presenter's Affiliation: Harvard Radiation Oncology Program


  • Limited data exist comparing contemporary technologies in the treatment of prostate cancer
  • Analysis of SEER Medicare data reveals that in the previous decade the use of IMRT, compared to 3D conformal radiation therapy (3D-CRT), increased dramatically despite increased costs and lack of randomized data demonstrating superior outcomes
  • A recently published SEER Medicare data reported that IMRT compared with proton therapy was associated with less gastrointestinal morbidity
  • The purpose of this report was to evaluate patient-reported outcomes for quality of life (QOL) from 3 modern cohorts of patients treated with 3D-CRT, IMRT or proton beam therapy

Materials and Methods

  • Patient report outcomes were collected using 2 validated quality of life instruments: Expanded Prostate Cancer Index Composite (EPIC) for IMRT patients and Prostate Cancer Symptoms Index (PCSI) for 3D-CRT and proton beam therapy patients.
  • Mean QOL scores for bowel, urinary irritation and sexual function were compared among the 3 different modalities at baseline, first follow-up (2-3 months), at 12 months and at 24 months after completing radiation therapy.
  • Clinically meaningful differences in QOL scores were defined as those exceeding half the baseline standard deviation


  • There were 123 patients treated with 3D-CRT from 1994-2000 at Harvard Affiliated Hospitals. Patients were treated to a total dose of 66.4-79.2 Gy with a 10 mm margin around the prostate gland
  • There were 153 patients treated with IMRT from 2003-2006 at 9 hospitals. Patients were treated to a total dose of 75.6-79.2 Gy with a 5-10 mm margin around the prostate gland
  • There were 94 patients treated with proton beam therapy from 2004-2008 at Massachusetts General Hospital. Patients were treated to a total dose of 74-82 Gy with a 5 mm margin around the prostate gland
  • Baseline patient characteristics: Patients treated with proton therapy were slightly younger (64 yo for proton therapy, 69 yo IMRT, 70 yo 3D-CRT, p<0.001)
  • Bowel QOL Scores: At the first follow-up, patients treated with 3D-CRT or IMRT had clinically significant decrease in bowel QOL. Patients treated with proton therapy did not have decreased bowel QOL at their first follow-up visit. At 24 months, all three groups had clinically significant decreases in their bowel QOL
  • Urinary Irritation QOL Scores: Scores were lower in all three groups at the first follow-up. This was clinically meaningful in the IMRT group, but the IMRT patients returned to baseline at 24 months. Patients in the proton beam group demonstrated a clinically meaningful decrease in QOL at 12 months, but returned to baseline at 24 months.
  • Sexual Function QOL Scores: Scores were lower in all three groups at 24 months, but this was not clinically meaningful

Author's Conclusions

  • Proton beam therapy appears to be associated with better early bowel QOL compared to 3D-CRT and IMRT, with similar mild effects at later time points
  • The data suggest transient differences in patient-report outcomes between IMRT and proton beam therapy with urinary irritation quality of life. All groups returned to baseline urinary quality of life at 2 years.
  • The authors acknowledge the limitations of the study including the retrospective nature of the study and the different follow-up periods between the groups
  • The authors conclude with the rationale for a randomized control trial, noting that Massachusetts General Hospital and University of Pennsylvania have partnered to launch a trial randomizing low and intermediate-risk prostate cancer patients to IMRT vs. proton beam radiation to evaluate QOL outcomes, cost-effectiveness and physics and radiobiology endpoints.

Clinical Implications

  • Proton beam therapy is a relatively new radiation treatment modality for the treatment of prostate cancer that can theoretically reduce acute and long-term side effects of treatment through normal tissue sparing. While this form of treatment is theoretically advantageous, it is expensive, and there has been no randomized evidence demonstrating a clinical benefit to proton therapy. Although in the previous decade there was no randomized evidence demonstrating a benefit to IMRT over 3D-CRT, when IMRT emerged as novel treatment, this form of treatment was readily accepted and reimbursed by insurance companies.
  • The authors present quality of life outcomes in bowel, urinary and sexual function in patients undergoing 3 different modalities of radiation treatment: 3D-CRT, IMRT and proton beam therapy. They found improved early bowel QOL in patients treated with proton therapy.
  • Interestingly, patients with 3D-CRT did not have clinically significant decreases in their urinary QOL, while the patients treated with IMRT had a decrease at 2-3 months after treatment and the patients treated with proton beam therapy had a decrease at 12 months. The decreases in QOL were transient as all groups returned to baseline at 24 months. This finding may be related to the lower radiation doses delivered to the patients treated with 3D-CRT.
  • It is unclear how the patients were queried in this study. The authors note that the study is retrospective, but it is unclear if the data was collected prospectively. If the data was not collected prospectively, it is likely that the data are subject to recall bias.
  • The study used 2 different quality of life instruments. The patients treated with proton therapy and 3D-CRT were assessed with PCSI and patients treated with IMRT were assessed with EPIC. This likely results in confounding of the results since the endpoints are measured differently.
  • The study evaluates sub-acute toxicity, not acute toxicity. During prostate cancer radiation treatment, patients experience significant side effects during treatment. These side effects slowly improve for most patients with time after the completion of treatment. The study’s first time point was 2-3 months after treatment. When comparing different treatment modalities and QOL, assessing acute toxicity is essential
  • The data that the authors present are interesting and differ from the previously published SEER Medicare data. The difference in reported outcomes further demonstrates the need for a randomized controlled trial evaluating proton beam therapy and IMRT in patients with prostate cancer, which is currently being launched by Massachusetts General Hospital and University of Pennsylvania.