Secondary treatment for prostate cancer shows wide regional variations

Published earlier this year (Cancer 2006; 107:258-65), the study linked the National Cancer Institute's Surveillance, Epidemiology, and End Results registry with the Medicare database for the years 1991 to 1999 to identify men with nonmetastatic prostate cancer who underwent primary treatment with radical prostatectomy or radiation therapy (external beam and/or brachytherapy with or without neoadjuvant hormones) and those who went on to receive secondary therapy through 2001. A total of 65,716 men who received primary therapy were eligible for inclusion in the study; 10,200 (15%) of those individuals received secondary therapy.

Using Cox proportional hazard techniques to analyze relationships between various demographic, socioeconomic, and clinical characteristics and receipt of secondary therapy, only geographic region, tumor grade, and year of diagnosis were found to have significant predictive value, regardless of the initial form of treatment.

"Our finding that where a man lives makes as much difference as tumor grade in how he is treated is a little disappointing as it reflects treatment decision ambiguity and the lack of good evidence on how best to treat prostate cancer after primary therapy. As such, it also serves as a call for collaboration among the multiple specialties that treat prostate cancer to organize well-designed studies that will provide data to answer that question."

The study was part of the Urologic Diseases in America Project being conducted by investigators at UCLA with support from a National Institutes of Health grant.

Difference seen in later years

For the study, secondary therapy was defined as receipt of radiation therapy or androgen deprivation therapy (ADT) 12 months after radical prostatectomy, ADT continued for more than 3 years after radiotherapy, or brachytherapy occurring at least 295 days after the last radiotherapy session.

"It cannot be said for sure that the men identified in our study as having secondary therapy were being treated because of a recurrence versus with adjuvant therapy. However, regardless of intent, these men underwent two, and sometimes three therapies. Each therapy carries a monetary cost as well as quality of life implications," Dr. Krupski said.

Data were analyzed with the men divided into two cohorts based on whether they received surgery or radiation therapy as primary intervention. Using men with grade 1 tumors as a reference group, those with grades 2, 3, and 4 tumors were between 1.5 and 5.6 times more likely to receive secondary therapy across both primary treatment groups.

Among the men who underwent primary radical prostatectomy, diagnosis after 1996 was associated with a lower likelihood of secondary therapy. One explanation for that finding is that widespread use of PSA screening in the modern era has enabled early detection and treatment of prostate cancer to reduce the proportion of men who need additional therapy, Dr. Krupski noted.

"However, the caveat to that reasoning is that lead time bias may also be influencing the study's results. Since prostate cancer is often an indolent malignancy, we may find as the data mature that these men experience recurrence and a need for secondary therapy," she explained.

In the radiation therapy subgroup, the likelihood of secondary therapy increased the later the year of diagnosis. That association might be accounted for by dissemination of the results of a randomized controlled trial from the Radiation Therapy Oncology Group showing a survival benefit associated with adjuvant hormone ablation administered for 3 years in men with high-risk disease (N Engl J Med 1997; 337:295-300).