Trial Information

CSP #553 - Adjuvant Therapy in Prostate Carcinoma Treatment (CAP)

VA Cooperative Study #553 is designed to prospectively evaluate the efficacy of early
adjuvant chemotherapy using docetaxel and prednisone added to the standard of care for
patients who are potentially cured by radical prostatectomy but who are at high risk for
relapse. The standard of care is surveillance, with the addition of androgen deprivation at
the time of biochemical relapse. This study will assess the effect of adding early
chemotherapy to the standard of care on progression free survival in veterans at high risk
for progression after prostatectomy.

The ability of radical prostatectomy to cure prostate cancer and to therefore prevent the
morbidity and mortality associated with progression to metastatic disease depends on
effectively treating both local and potential systemic disease. In the United States
alone, over 80,000 men per year are treated with prostatectomy to cure their disease.
Because 20% of these men will be found to have locally advanced or high-grade disease, they
will be at risk for relapse and morbidity from their prostate cancer. Although androgen
deprivation, radiation therapy, and chemotherapy have been considered potentially effective
adjuvant modalities for localized prostate cancer, there are no randomized studies that
support the utility of any of these treatments as a standard of care. Ultimately, it is
androgen independent prostate cancer, which causes morbidity for these patients. Docetaxel
based chemotherapy has been shown to prolong survival and induce responses in up to 80% of
patients with androgen independent disease, generating enthusiasm for the use of
chemotherapy early in the treatment of prostate cancer. This study is designed to test the
value of adjuvant chemotherapy in improving progression free survival, which is critical in
preventing morbidity and mortality from relapse in patients with clinically localized, but
high risk, prostate cancer.

After patients are stratified for PSA, Gleason score, tumor stage, the presence of positive
margins, and the planned use of adjuvant radiation therapy, this study will prospectively
randomize 636 patients from 30 VA sites, after prostatectomy, to the standard of care or to
docetaxel and prednisone administered every 3 weeks for 18 weeks. Patients would then be
observed with PSA for a minimum of one and a maximum of five years. The study is designed
with 90% power to detect a reduction in the 5-year progression rate from 60% to 45% (15%
absolute difference, 25% relative difference).

Prostate cancer is the leading cause of malignancy for veterans, and the second leading
cause of death. Patients with high risk, localized disease account for 70% of all cancer
deaths in patients treated for cure with radical prostatectomy. Effective adjuvant therapy
is critical to reducing suffering and death from prostate cancer. The VA Cooperative Studies
Program is uniquely placed to address this question. The VA has a longstanding history of
important studies in prostate cancer, which have significantly changed the way urologic
oncologists treat patients with this disease. The incidence of prostate cancer in our
older, male population is substantial, the number of veterans treated with prostatectomy
continues to rise, and the incidence of high risk prostate cancer in veterans is greater
than that typically found in the community. For all of these reasons, carrying out this
study within the VA through the VA Cooperative Studies Program is the optimal way to
determine whether adjuvant chemotherapy will benefit men with high risk prostate cancer.