Presenter: Anthony Zietman, MD Presenter's Affiliation: Massacusetts General Hospital Type of Session: Scientific
While historical results in treatment of prostate cancer have traditionally been fairly good, treatment failures still occur, as seen with increasing follow-up on older trials. Therefore, efforts have been underway to improve long-term tumor control. One technique, employed by various groups, has been to escalate radiation dose to the prostate, while sparing adjacent normal tissues,with the use of improved modern radiotherapy techniques. This paper reports the results of one such effort, using proton radiotherapy as a boost, in conjunction with traditional photon therapy. Patients were randomized between 70.2 GyE and 79.2 GyE of photon/proton radiotherapy.
Materials and Methods
This study enrolled 393 patients at two centers (Massachusetts General Hospital and Loma Linda University Medical Center).
Patients had biopsy-provien T1b-T2b prostate cancer and PSA of <15 ng/mL.
75.3% had Gleason scores of 6 or less, 15.3% Gleason 7, and 8.4% Gleason 8-10. Sixty-one percent had T1c tumors. Median PSA was 6.3 ng/ml. Median age was 67. None had clinically-involved lymph nodes.
Patients were randomized to proton boost up-front, receiving 19.8 GyE or 29.8 GyE. Gray-Equivalent dose was computed using an RBE of 1.1 for the proton beams. Patients were treated with either a single perineal beam or via opposed lateral technique with the patients in the supine position, at the discretion of the treating institution. A rectal balloon was utilized daily during treatment to minimize radiation dose to the rectum. CTV included the prostate with a 5 mm margin.
All patients then received 50.4 Gy to the pelvis in 1.8 Gy fractions, delivered via four-field technique. CTV included the prostate and seminal vesicles, plus 1 cm margin.
No patients received androgen deprivation therapy.
Local failure was defined using both indirect and surrogate criteria: clinically through palpation; histologically after rebiopsy of a clinically benign prostate with rising PSA; or biochemically by a PSA of >1 ng/mL 2 or more years after treatment, without rebiopsy.
Biochemical failure was defined using the ASTRO definition.
393 patients were enrolled from January,1996 to March, 1999.
Median follow-up is 5.5 years in this intent-to-treat analysis.
97-98% of all patients received radiotherapy as assigned.
Time to PSA nadir was longer in the high-dose arm (40 months vs 28 months), though the nadir was lower in the high-dose group, with 60% of those patients achieving a nadir < 0.5 ng/mL, versus only 45% of patients in the lower-dose radiation arm.
Freedom from biochemical failure was 79% in the high-dose arm, versus 61% in the low-dose arm, with p < 0.001. When correcting for "backdating" in the ASTRO definition, the results were still consistent (86% vs 66%), still favoring the high-dose arm, with p<0.001.
On subgroup analysis, improved local control was demonstrated for both low-risk patients and intermediate/high-risk patients, which again held up when controlled for "backdating" on the ASTRO definition.
Acute toxicities were not statistically different in the two arms, though the high-dose group did have a higher rate of grade 2 GI toxicity. There was no difference in grade 3 or higher toxicity between the two arms.
There were no differences between the groups in terms of overal survival or freedom from distant metastases.
Dose escalation can be achieved without increasing acute/late morbidity, using a combination proton/photon technique.
PSA nadir values are lower in patients in the high-dose group.
There is an increased biochemical disease-free survival/local control for all risk groups, especially the low-risk patients (who comprise the majority seen in the era of routine PSA screening).
While no difference has yet been seen in terms of overall survival or freedom from distant metastases, five years of follow-up are not sufficient to make scientific claims in this regard.
This study confirms data from at least one other major trial that increasing dose to the prostate/tumor can lead to improved tumor control. While the technique used in this study (proton boost) is available in only a few centers internationally, a number of other techniques are available to radiation oncologists at nearly all centers which can effectively deliver higher doses of radiation to the prostate while sparing normal tissues (IMRT, brachytherapy).
Remaining questions, not evaluated by these researchers, concern the role of androgen deprivation therapy in conjunction with higher-dose radiotherapy. The use of androgen ablation therapies has been shown to be of benefit in both high-risk patients on a prior RTOG study and in a recent multi-institutional trial of intermediate-risk prostate cancer patients.
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.