Hypofractionated Intensity Modulated Radiotherapy (70 Gy at 2.5Gy Per Fraction) for Localized Prostate Cancer: Long-Term Outcome Results

English

Reviewer: Chika Madu, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 20 de octubre del 2005

Presenter: V.V. Thakkar
Presenter's Affiliation: Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, OH
Type of Session: Scientific

Background

The principle of α /β has always been instrumental in guiding radiation therapy fractionation and doses. With the prostate having an α /β of 1.5-3, while the rectum and bladder are 4-6, and 7 respectively, hypofractionation in localized prostate cancer could be an alternative approach to standard treatment. This study reports the long term outcomes from hypofractionated radiotherapy (HFRT) study for localized prostate cancer

Materials and Methods

100 patients accrued from 1998-1999 with stage T1-T3 disease were evaluated
The lateral and posterior margins on the prostate ± seminal vesicles were 8mm and 4mm posteriorly. All other margins were 5mm
Treatment was delivered using a 5-field IMRT plan, prescribed to 70Gy at 2.5Gy per fraction over 5.5 weeks
Transabdominal ultrasound was used daily to localize the prostate
36, 30, and 34 patients had low, intermediate, and high risk disease respectively
51 patients received concurrent hormonal therapy with a 6-month maximum duration
Median follow up was 66 months (3-75 months)
Acute and late toxicity (RTOG scores) as well as biochemical relapse free survival (bRFS) were the endpoints
The ASTRO biochemical failure definition (A-bRFS) as well as the alternate nadir +2ng/ml definition (N-bRFS) were evaluated

Results

At a median follow up of 66 months, there were no significant differences in the A-bRFS or N-bRFS rates (85% vs. 88%)
For low, intermediate, and high risk disease, the 5-year A-bRFS rates were 97%, 88%, and 70% respectively, while the N-bRFS rates were 97%, 93%, and 75% for the same groups.
The acute rectal toxicity rate (grade 1-2) was 80%, while the acute urinary toxicity rate (grade 1-2) was 91%
At 5 years, the actuarial late RTOG rectal toxicity rate was 3% and 10% for grades 2 and 3 late rectal toxicity respectively
The actuarial late RTOG grade 3 urinary toxicity rate at 5 years was 1%
There were no grade 4 toxicities
If greater than 10cc of the rectum received ≥70Gy, the rate of grade 2-3 rectal toxicity doubled from 8% to 16%

Author's Conclusions

The long-term results of this hypofractionation regimen are excellent
Long-term bRFS rates are encouraging
Urinary and rectal toxicities are limited
High-dose hypofractionation is an alternative to dose escalation for localized prostate cancer
This treatment regimen is more convenient for patients due to shorter treatment time

Clinical/Scientific Implications

This study explores the idea that if the alpha-beta ratio for the prostate is lower than that of the surrounding normal tissues (rectum and bladder), then it would be logical to use hypofractionation for the treatment of localized prostate cancer. At a dose of 70Gy in 2.5Gy fractions, the EQD2 to the prostate is 83Gy. At 5 years, the rectal and urinary toxicities reported are acceptable. An advantage for the patient is a decreased overall treatment time. The challenge then is to determine the optimal fractionation schedule that will give excellent disease control while limiting treatment toxicities. It is important to stress that even grade 2 rectal toxicities significantly affect the quality of life for many patients. An upcoming study in this area will be RTOG 0415 which will randomize patients with prostate cancer (T1-2, GS 2-6, PSA <10) to 73.8Gy/41fractions vs. 70Gy/28 fractions.