Irradiation Produces Durable Survival in Prostate Cancer

Roxanne Nelson

March 05, 2013

In prostate cancer, radiation therapy and radical prostatectomy produce "durable disease control." In fact, 15-year disease-free survival rates with the 2 treatments are similar, according to a new study published in the March issue of the Journal of Urology.

However, the researchers found that prostate cancer can recur after many years. Therefore, they recommend that patients be followed for at least 15 years after their initial treatment.

"Some physicians feel that after 10 years, you don't have to continue follow-up, but we found that 5% of recurrences happen after 10 years," explained lead author Frank A. Critz, MD, founder and medical director of Radiotherapy Clinics of Georgia. "We've seen some recurrences after 15 years, and we have 1 patient with disease recurrence after 17 years," he noted.

On the basis of their study, Dr. Critz believes that follow-up should be at least 15 years, "but personally, I think 20 years if preferable.... If the PSA [prostate-specific antigen] is below 0.2 ng/mL at 20 years, then the PSA checks can be discontinued."

"After 20 years, we have not seen a recurrence," he noted.

Dr. Critz explained that, at his facility, patients have their PSA checked every 6 months for 10 years; if the PSA is below 0.2 ng/mL at 10 years, they go to annual testing.

Aggressive Late Recurrences

The prostate program at Radiotherapy Clinics of Georgia is the only one of its kind to have gathered and maintained a clinical-records database in a consistent and comprehensive manner for all patients over a 30-year period, according to a release. In their study, Dr. Critz and colleagues evaluated the 25-year cure rates with radiation therapy; disease-free survival rates were 75% at 10 years, 73% at 15 years, 73% at 20 years, and 73% at 25 years.

For men who received a transperineal implant followed by external-beam radiation therapy from 1995 to 2000, 15-year disease-free survival was 79%.

Of the 313 men who received radiation treatment 16 to 25 years ago and whose disease recurred, the majority of recurrences (75.4%) developed in the first 5 years after treatment. However, 5.0% developed after the 10-year follow-up.

Dr. Critz explained that some of these late recurrences have been aggressive cancers. Of the 31 patients who did have a late recurrence, 3 required hormone therapy within 36 months. All of these patients had PSA levels of 0.1 ng/mL or less 6 to 12 months prior to disease recurrence.

It was expected that such late recurrences would be indolent, considering the time lag. However, in 1 patient who had a stable PSA level for 12 years (below 0.1 ng/mL), it "took off like a rocket," he said.

In a second patient, PSA went from almost 0 to 0.5 ng/mL in a 6-month period. "We thought it might have been a lab error, but then it went up to 50.0 ng/mL 6 months after that," Dr. Critz reported. "The man had an aggressive disease with bone metastasis."

Surgical Definition

In their study, Dr. Critz and colleagues used the surgical definition of prostate cancer recurrence (a PSA cutoff of 0.2 ng/mL), which is much stricter than the the American Society for Radiation Oncology (ASTRO) definition of recurrence used in most radiation therapy studies (a 2.0 ng/mL increase in PSA above nadir).

Results are significantly better when the ASTRO definition is used to determine disease-free survival rates after radical prostatectomy and irradiation than when the surgical definition is used. In one study, 15-year disease-free survival was 90% when the ASTRO definition was used, but was 68% when the surgical definition was used (J Urol. 2002;168:1419-1422).

"There really should be one definition and one standard that we use," said Dr. Critz, "and it should be the surgical one."

Comparable to Surgery

Dr. Critz and colleagues evaluated whether there is "durable control" of prostate cancer (PSA < 0.2 ng/mL) more than 20 years after being treated with radiation therapy.

Their cohort involved 3546 hormone-naïve men with prostate cancer who were treated from 1984 to 2000 with 125I implantation followed by external-beam radiation. The initial cohort received retropubic implants, but as the technology improved, a transperineal template/ultrasound-guided approach was used (n = 2875).

Recurrence was defined as a PSA increase of more than 0.2 ng/mL or a PSA nadir greater than 0.2 ng/mL. Median follow-up time was 11 years (range, 3 months to 26 years).

The researchers found that overall disease-free survival was comparable to that from 2 studies with 15-year follow-up data after radical prostatectomy (J Urol. 2002;168:1419-1422; Urology. 2005;66[5 suppl]:83-94).

Dr. Critz and colleagues found 10-year disease-free survival to be 75%, whereas it was 77% in each of the 2 prostatectomy studies. They found 15-year disease-free survival to be 73%, compared with 68% to 75%.

It is not known why prostate cancer can recur after such a long time. "We are just beginning to have long-term patients, and are just beginning to study them," said Dr. Critz. "We are in our infancy with this."

J Urol. 2013;189:878-883. Abstract