Veterans Affairs Cooperative Studies Program Study #553: Chemotherapy After Prostatectomy for High-risk Prostate Carcinoma: A Phase III Randomized Study

Daniel W. Lin, Mei Chiung Shih, William Aronson, Joseph Basler, Tomasz M. Beer, Mary Brophy, Matthew Cooperberg, Mark Garzotto, W. Kevin Kelly, Kelvin Lee, Valerie McGuire, Yajie Wang, Ying Lu, Vivian Markle, Unyime Nseyo, Robert Ringer, Stephen J. Savage, Patricia Sinnott, Edward Uchio, Claire C. YangR. Bruce Montgomery

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: 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. Objective: 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%. Conclusions: 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). Patient summary: In this randomized trial, we tested whether addition of chemotherapy to surgery for high-risk prostate cancer decreased the risk of prostate-specific antigen rise after surgery. We found no benefit from docetaxel given after radical prostatectomy, although some subgroups of patients may benefit.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalEuropean Urology
Volume77
Issue number5
DOIs
StatePublished - May 2020
Externally publishedYes

Keywords

  • Adjuvant
  • Chemotherapy
  • Clinical trial
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

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    Lin, D. W., Shih, M. C., Aronson, W., Basler, J., Beer, T. M., Brophy, M., Cooperberg, M., Garzotto, M., Kelly, W. K., Lee, K., McGuire, V., Wang, Y., Lu, Y., Markle, V., Nseyo, U., Ringer, R., Savage, S. J., Sinnott, P., Uchio, E., ... Montgomery, R. B. (2020). Veterans Affairs Cooperative Studies Program Study #553: Chemotherapy After Prostatectomy for High-risk Prostate Carcinoma: A Phase III Randomized Study. European Urology, 77(5), 563-572. https://doi.org/10.1016/j.eururo.2019.12.020