Higher Radiation Dose Reduces "Biochemical Recurrence" of Prostate Cancer
Prostate cancer, high-dose radiation, conformal radiotherapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
After nearly nine years of follow-up, men with early-stage prostate cancer who received higher doses of radiation were less likely than men who received the conventional dose to have rising levels of prostate-specific antigen (PSA)—a phenomenon referred to as “biochemical recurrence” that may predict actual recurrence 15 years or more in the future. The benefit associated with a higher dose of radiation was most evident in men with a low risk of recurrence.
Journal of Clinical Oncology, published online ahead of print, February 1, 2010 (see the journal abstract).
Most cases of prostate cancer now diagnosed in the United States are detected at an early stage. One of the treatment options for men with early-stage prostate cancer is radiation to kill the tumor cells (radiotherapy).
Even after radiation treatment, however, prostate cancer can come back (recur). Several studies have shown that higher doses of radiation make recurrence less likely, although they increase the risk of some side effects, including intestinal problems and difficulty with erections and urination.
Studies of patients with advanced prostate cancer have suggested that “conformal” radiation therapy techniques might allow radiologists to safely deliver higher doses of radiation and, thus, cut down on recurrences. Conformal techniques produce tight three-dimensional radiation fields, leaving more of the normal tissue untouched. The tighter targeting is also thought to permit the safe delivery of greater amounts of radiation. Conformal radiation therapy may be delivered by high-energy x-rays (photon-beam radiation) or protons (proton-beam radiation).
The phase III trial described here was designed to test whether giving higher-than-conventional doses of radiation with conformal radiation techniques would improve prostate cancer control in patients with early-stage disease. Results after a median follow-up period of five years were published in 2005. In the current publication, researchers report results after median follow-up of nearly nine years.
Between January 1996 and December 1999, researchers at Loma Linda University Medical Center (California) and Massachusetts General Hospital (Boston) enrolled 393 patients with stage II prostate cancer that had not spread (metastasized) beyond the prostate gland. All of the patients were treated with both photon- and proton-beam conformal radiation techniques: 197 patients received a total dose of 70.2 Gy, which is the conventional amount, and 195 received a total dose of 79.2 Gy. The patients’ median age was 67 in the group receiving conventional doses and 66 in the group receiving high doses. Most of the patients were white.
While they were receiving radiation, patients underwent no other treatment (including hormone therapy) for their cancer. Researchers followed them for a median of 8.9 years, periodically testing the patients’ prostate-specific antigen (PSA) levels and examining their prostates. Biopsies were performed in some cases to test for local recurrence. Researchers asked the patients’ doctors about the severity and number of side effects.
Since the design of this trial in 1995, researchers have developed ways to categorize men according to the risk that their prostate cancer will recur. According to these categories, 227 (58%) of the men enrolled in the study had a low risk of recurrence, 144 (37%) had an intermediate risk, and 17 (4%) had a high risk.
The lead author of the study is Anthony L. Zietman, M.D., of Harvard Medical School and Massachusetts General Hospital.
Men treated with the higher radiation dose were more likely to be free from biochemical recurrence (measured by a rising PSA level) than men who received the conventional dose. Biochemical recurrence was seen in 32 percent of the men in the conventional-dose arm but only 17 percent of those in the high-dose arm. When the men were analyzed separately according to risk group, a statistically significant long-term advantage of higher-dose radiation therapy was seen only in patients with a low risk of recurrence, although there was some evidence of benefit for men of intermediate risk.
Few men reported serious side effects such as intestinal problems or difficulty with erections, and the numbers of men reporting such side effects were about the same in both the conventional and high-dose treatment groups.
Overall survival was similar in the two treatment groups.
Unlike some other studies of high-dose radiation for prostate cancer, which used photon radiation only, radiation in this study was delivered using both photon and proton beams. However, it was the dose of radiation that was compared and not the radiation source.
“The design of the current study does not allow one to draw any inference about the efficacy of proton [radiation] therapy vis-a-vis photon [radiation] therapy,” writes W. Robert Lee, M.D., of Duke University Medical Center, in an accompanying editorial.
The trial also did not show an improvement in overall survival with the higher dose of radiation. Longer follow-up times may be necessary to show an improvement in this outcome.
Finally, the trial was not designed to assess outcomes according to the participants’ predicted risk of recurrence. Therefore, the differences among risk groups will need to be confirmed in future studies.
The findings of this randomized clinical trial are consistent with a trend already well established in the United States toward the use of higher radiation doses in the treatment of early-stage prostate cancer, says Aradhana Kaushal, M.D., of NCI’s Radiation Oncology Branch.
However, in this study only patients at low risk of recurrence showed a statistically significant biochemical benefit from high-dose radiation therapy at this follow-up time, Dr. Kaushal notes. Moreover, for some patients with low-risk prostate cancer, active surveillance—closely monitoring a patient’s condition but holding off on treatment until symptoms appear or test results show that the cancer is changing—may be an equally viable option.
“Active surveillance needs to be on physicians’ minds when they counsel patients about potential treatment options,” says Dr. Kaushal. “It should definitely be at least one of the considerations in older men who have certain types of low-risk prostate cancer and other coexisting health problems.” Because some types of low-risk prostate cancer progress very slowly, there are cohorts of men with low-risk prostate cancer who are likely “to die with prostate cancer, rather than of it,” she adds.
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