Chemotherapy After Prostatectomy for High-Risk Prostate CarcinomaEuropean Association of Urology

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TAKE-HOME MESSAGE

•This was a phase III randomized trial comparing adjuvant docetaxel plus prednisone with the standard of care (observation) in men at high risk of recurrence following radical prostatectomy. In the 298 patients recruited, median progression-free survival was not significantly longer in the treatment group compared with the control group (55.5 months vs 42.2; P=.21). Improved progression-free survival was observed in two prespecified subgroup analyses. These were patients with tumor stage ≥T3b and Gleason score ≤7.

•There was no significant improvement in survival with the use of adjuvant docetaxel in this high-risk population following surgery. The study had limited power due to poor accrual. Some subgroups did appear to benefit from the intervention. Further study is needed to identify the appropriate patients to consider for adjuvant chemotherapy in this setting.

– Jeffrey J. Tosoian, MD, MPH

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.

European Association of Urology

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

Eur Urol 2020 Jan 07;[EPub Ahead of Print], DW Lin, MC Shih, W Aronson, J Basler, TM Beer, M Brophy, M Cooperberg, M Garzotto, WK Kelly, K Lee, V McGuire, Y Wang, Y Lu, V Markle, U Nseyo, R Ringer, SJ Savage, P Sinnott, E Uchio, CC Yang, RB Montgomery

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.