Planned radical prostatectomy within 8 weeks of preoperative radiotherapy is well tolerated and may result in downstaging of the disease, according to results of a phase I study.
Early results of this ongoing trial are encouraging, without major intraoperative or immediate postoperative morbidity, said lead author Bridget F. Koontz, MD, assistant professor of radiation oncology at Duke Medical Center, Durham, NC.
Preoperative radiotherapy has been used successfully in some cancers to improve resectability, local control, and disease-free survival compared to postoperative radiotherapy, but has been avoided in prostate cancer.
Radiotherapy was delivered to the prostate, seminal vesicles, and pelvic lymph nodes in a dose-escalation manner from 39.6 Gy to 45 Gy, with a third-level boost of 5.4 Gy to the prostate and seminal vesicles in one cohort of men. The men were followed for a median of 16 months.
"There were no unexpected toxicities as far as rectal injury or anastamotic leaks, and the rate of incontinence was what you would expect postoperatively," Dr. Koontz said. "The three patients who had urinary incontinence only had a median follow-up of 8 months, compared to 16 months for the whole group, so the majority of patients with longer follow-up did regain continence."
Six patients experienced complete erectile dysfunction, two required blood transfusions during surgery, one developed a lymphocele with pelvic pain after surgery, and one had an extended catheterization but passed a voiding trial on postoperative day 20.
Six of the eight patients had a first postoperative PSA level less than 0.1 ng/mL.
Treatment failed in two patients with a PSA rising above 0.2 ng/mL; neither had positive margins.
"One had a preoperative PSA of 42.0 ng/mL, and those patients are now being treated with salvage hormonal therapy," Dr. Koontz said.
'Trend toward downstaging'
When compared to a cohort that underwent RP without preoperative radiation, "We see a trend toward downstaging with preoperative radiation," she said. The rates of positive surgical margins, extracapsular extension, and seminal vesicle involvement, and postoperative PSA levels all appear to be less with preoperative radiation.
"We have three more patients to enroll in the phase I trial, and then we move ahead to a multi-institutional phase II study," Dr. Koontz added. "There's a lot of discussion now that for high-risk patients, postoperative radiation at some time point is appropriate. This study builds off of other studies in other cancers that suggest that preoperative radiation may be more effective than postoperative radiation at a lower dose.
"The advantage in prostate cancer is that high-risk patients may be able to avoid hormonal therapy, and they may have a higher rate of resectability with negative margins compared to those who go straight to prostatectomy."