May 2010 Newsletter Articles

STUDY WEIGHS COMPARATIVE EFFECTIVENESS OF LOW-RISK PROSTATE CANCER TREATMENTS

When it comes to treating low-risk prostate cancer, a new comparative effectiveness study has concluded that the various approaches - including active surveillance, surgery and radiation therapy - result in similar overall survival and tumor recurrence rates. However, compared with the immediate treatment options, active surveillance yields both a comparative net health benefit and more quality-adjusted years for men age 65 and older, according to the economic model used in this study.

Researchers at the Institute for Clinical and Economic Review, which is based at the Massachusetts General Hospital's Institute for Technology Assessment, examined the published evidence on different approaches being used to manage low-risk prostate cancer and the results of a simulation model that can project the long term effects of each approach for large populations. Their review also included a comparison of the relative economic cost of each approach. The literature review and analysis were aided by an evidence review group of nearly 50 members that included top prostate cancer specialists from across the country, patient advocates, and representatives from medical device, pharmaceutical and health insurance companies.

Their task was complicated, the reviewers acknowledged, by a lack of published trials that compared the different options head-to-head, as well as other factors. In addition to traditional open surgery (or radical prostatectomy) they assessed the clinical cost and effectiveness of robotic and traditional laparoscopic prostatectomy, as well as of brachytherapy and intensity-modulated radiation therapy. Because of the limited published data on proton beam radiation therapy, a treatment for localized prostate cancer that has gained popularity, the reviewers called it "premature" to offer any "judgments about its relative benefit or inferiority to other options."

NC! Cancer Bulletin, 12 January 2010

PROSTATECTOMY IMPROVES OUTCOME OF SOME MEN WITH PROSTATE CANCER OVER WATCHFUL WAITING

Men with early prostate cancer who undergo radical prostatectomy have a lower rate of death due to prostate cancer than men who are followed without treatment, known as watchful waiting, according to a randomized controlled trial published on-line in the Journal of the National Cancer Institute.

The benefit from the surgery, with respect to prostate cancer death rates, remained constant beyond 10 years, but the overall death rates in the two groups were not statistically different. The applicability of the results to the current generation of prostate cancer patients is unclear, however, because few of the cancers treated in the trial were discovered by PSA (prostatespecific antigen) screening, a practice that is now widespread.

The Scandinavian Prostate Cancer Group launched the current trial in 1989 to examine the impact of radical prostatectomy on cancer-specific mortality relative to watchful waiting. In 2005, with a median follow-up 8.2 years, the researchers reported that men in the prostatectomy arm had lower rates of disease-specific mortality than those in the watchful waiting arm.

The investigators were interested to know if the prostate cancer mortality difference would continue to increase with longer follow-up. Thus far, this is the only completed randomized trial comparing the two treatment options. Lars Holmberg, MD, of the Kings College Medical School in London and colleagues from Finland and Sweden continued to follow the men for an additional three years.

With a median follow-up of 10.8 years, the cumulative incidence rate for prostate cancer death was 13.5 percent in the surgery arm and 19.5 percent in the watchful waiting arm, for an absolute reduction of 6 percent. The benefit, in terms of absolute risk reduction, did not increase after the first 10 years following treatment. For those patients followed at least 12 years, 12.5 percent of the men in the surgery group died due to prostate cancer compared with 17.9 percent of the men in the watchful waiting group, for an absolute reduction of 5.4 percent. Overall mortality

SIMILAR SURVIVAL WITH SALVAGE SURGERY (RP) AND RADIOTHERAPY (RT)

There are several treatments for localized prostate cancer patients, but no randomized study has compared any RT with RP. Consequently, decisions on local treatment are often based on patients' and doctors' preferences and assumptions, explain HG van der Poel and colleagues from the Netherlands Cancer Institute in Amsterdam.

To investigate further, the researchers studied 32 patients who underwent salvage RP and 41 who received salvage RT for cT1-c-T2 prostate cancer.

Local biopsy recurrence and a life expectancy of over 10 years was the basis for salvage RP, while salvage RT was performed in patients with a PSA level that had risen above 0.1 ng/ml and no systemic disease. PSA recurrence occurred in 39% of salvage RT patients after an average interval of 38.4 months and in 69% of salvage RP patients after an average of 45.4 months, the team notes in the Journal of Surgical Oncology.

Ten-year PSA recurrence-free survival after primary treatment was nonsignificantly greater in salvage RP patients than that seen in the salvage RT group, at 55% versus 44%. Prostate cancer-specific survival was also nonsignificantly higher for salvage RP, at 93% versus 89% for salvage RT.

PSA recurrence-free survival was predicted by biopsy Gleason score prior to primary treatment and by PSA doubling time prior to salvage treatment on univariate analysis.

The necessity of wearing urinary incontinence pads was less likely with salvage radiotherapy than salvage surgery, at 13% versus 56%, and erectile dysfunction was also less common, at 61% versus 81%.

"This retrospective analysis shows that long-term PSA recurrence-free survival after combined treatment for cT1-2 prostate cancer seems to be independent of the order of radiotherapy and prostatectomy," the team concludes.

Med Wire News, 10 April 2008

at 12 years, however, was not statistically significantly different in the two arms at 32.7 percent and 38.5 percent, respectively.

"Contrary to our predictions based on shorter follow-up the absolute difference in cumulative incidence of distant metastasis and prostate cancer death did not further increase after 7 years of follow-up the authors write.

The authors note that it is not clear whether their data are applicable to men whose cancer is detected in the era of PSA screening because most of the men in their trial had palpable tumors at diagnosis.

"In settings with a large proportion of PSA-detected tumors, the relative reduction in risk of death following radical prostatectomy might be somewhat larger or similar to that in our study, but the absolute reduction would be smaller," they write.

In an accompanying editorial, Timothy Wilt, MD, of the Minneapolis VA Center for Chronic Disease Outcomes Research also raises that issue but concludes that the results are applicable to a subset of current prostate cancer patients.

"These results demonstrate that among men younger than 65 years whose prostate cancer is detected by methods other than PSA testing (e.g., due to a digital rectal examination to evaluate urinary or other symptoms), cure with radical prostatectomy is possible, may be necessary, and should generally be recommended," he writes.

He notes that the current trial is only the first in a series that are evaluating treatments for men with localized prostate cancer, and that at least one included patients whose tumors were discovered through PSA testing.

These trials and trials testing options between these two extremes will be important in guiding prostate cancer care in the future.

ScienceDaily, 13 August 2008