The Veterans Affairs Cooperative Studies Program study #553 was designed to evaluate the efficacy of adjuvant chemotherapy added to the standard of care (SOC) for patients who are at high risk for relapse after prostatectomy.
To test whether addition of chemotherapy to surgery for high-risk prostate cancer improves progression-free survival (PFS).
Design, setting, and participants
Eligible patients after prostatectomy were randomized to the SOC group with observation or to the chemotherapy group with docetaxel and prednisone administered every 3 wk for six cycles. Randomization was stratified for prostate-specific antigen, Gleason, tumor stage, and surgical margin status.
Outcome measurements and statistical analysis
The primary endpoint was PFS. Secondary endpoints included overall, prostate cancer-specific, and metastasis-free survival, and time to androgen deprivation therapy.
Results and limitations
A total of 298 of the planned 636 patients were randomized. The median follow-up was 59.1 mo (0.2-103.7 mo). For the primary endpoint, the two groups did not statistically differ in PFS (median 55.5 mo in the chemotherapy group and 42.2 mo in the SOC group; test adjusted for site via gamma frailty p=0.21; adjusted hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.58-1.11; p=0.18). Prespecified subgroup analyses showed benefit in PFS for patients with tumor stage ≥T3b (HR 0.54, 95% CI 0.32-0.92; p=0.022) and patients with Gleason score ≤7 (HR 0.65, 95% CI 0.43-0.99; p=0.046). Secondary endpoint analyses are hampered by low event rates. The most common adverse events (≥grade 3 related or possibly related to chemotherapy) included neutropenia (43%), hyperglycemia (20%), and fatigue (5%), with febrile neutropenia in 2%.
Adjuvant chemotherapy in high-risk prostate cancer using docetaxel and prednisone did not lead to statistically significant improvement in PFS for the intention-to-treat population as a whole. The analysis was challenged by lower power due to accrual limitation. Subgroup analyses suggest potential benefit for patients with Gleason grade ≤7 and stage≥pT3b (ClinicalTrials.gov number NCT00132301).
The Chemotherapy after Prostatectomy (CAP) study explored the use of a chemotherapy medication called docetaxel in patients who have undergone an operation to remove high-risk, localized (=restricted to the prostate) prostate cancer. The findings indicate that docetaxel doesn’t offer patients any survival advantages and thus should remain to be prescribed in case of metastatic cancer, cancer that has spread to other parts of the body, only. Docetaxel should not be used as a safety procedure after prostate cancer surgery.