A Prospective Phase I/II Study using Proton Beam Radiation to Deliver 82GyE to Men with Localized Prostate Cancer: Preliminary Results of ACR 0312

Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 24, 2008

Presenter: Anthony Zietman
Presenter's Affiliation: Massachusetts General Hospital, Boston, MA
Type of Session: Scientific

Background

Prospective randomized studies have shown dose escalation to be effective in prostate cancer
A previous study of dose escalation to 79.2 Gy utilized conformal photon therapy to 50.4 with a proton boost to the prostate
With prostate, as well as in other sites, dose escalation is typically associated with increased toxicity, increased conformality, or both
The purpose of this study is to assess the toxicity and efficacy of proton therapy alone to 82 GyE to the prostate

Materials and Methods

85 men were enrolled in this single-arm trial from 2004-2006 at Massachusetts General Hospital and Loma Linda University Medical Center
Median age was 63 years
All patients had T1-T2 tumors with PSA < 15 ng/dL
Patients were excluded when they had prior pelvic radiation therapy, history of urethral strictures, or were taking coumadin
There was no exclusion based on Gleason grade
All patients were treated with opposed lateral proton fields using 2 GyE daily fractions
A passive scattering proton beam was utilized
Daily guidance was achieved with either ultrasound BAT or fiducials
Margins to PTV were 1 cm with 0.5 cm posteriorly for the first 50 Gy and then the GTV alone was treated for the final 32 Gy with no additional margin
Primary endpoint was late grade 3-4 GU/GI toxicity on the RTOG scale
Secondary endpoints were both PSA and local failure
A supplemental endpoint was added for those patients treated at MGH as patients were given a validated questionnaire to report symptoms prior to radiation and 12 months following completion of treatment

Results

Median follow-up is 23 months
Acute grade 2+ toxicity rates were 1% and 14% for GI and GU respectively
Acute grade 3+ toxicity rates were 0% and 1% for GI and GU respectively
Late grade 2+ toxicity rates were 12% and 30% for GI and GU respectively
Late grade 3+ toxicity rates were 1% and 8% for GI and GU respectively
There were 2 grade 4 late toxicities, both in one single patient who experienced both hematuria and rectal ulceration
- This patient was noted to have a very large prostate
Among the 35 men who completed the quality of life questionnaire, a significant increase in obstruction/irritation and sexual dysfunction were noted at 12 months
- There were no significant changes in incontinence or bowel complaints

Author's Conclusions

82 GyE can be delivered using protons with acceptable morbidity at 2 years
Morbidity from protons is similar to that from conformal photon therapy
The author provided equipoise in stating that protons may be better, the same, or worse than photon therapy
Randomized comparison between proton and photon radiation therapy is warranted in prostate cancer to establish a direct comparison

Clinical/Scientific Implications

The optimal dose for prostate radiation therapy is not currently known
The tolerability of treatment appears to be related to both the technique of administration and the target dose
These data suggest acceptable toxicity with 82 GyE using opposed lateral fields and passively scattered proton beams
Care must be used in extrapolating these results into the general practice
- Margins used in this study were smaller for the final 32 Gy than in prior studies
- Small variations in pelvic positioning has the potential to significantly alter the dose distribution of a proton beam due to the differential of attenuation through bone
Long-term efficacy should be established, ideally through randomized data, prior to routine use of proton therapy for dose escalation in excess of 79.2 Gy