Researchers tested the addition of adjuvant chemotherapy to androgen suppression and radiotherapy in patients with localized high-risk prostate cancer.
The addition of adjuvant chemotherapy to androgen suppression and radiotherapy yielded improved survival outcomes in patients with localized high-risk prostate cancer, according to a randomized phase III study.
“Docetaxel-based chemotherapy has improved overall survival among men with castration-resistant cancer and recently among men with castration-sensitive prostate cancer,” wrote study authors led by Seth A. Rosenthal, MD, of Sutter Cancer Centers in Sacramento, California. “Clinical experience in other common malignancies suggests that chemotherapy may be more effective if used earlier in the course of disease.”
The new phase III trial included a total of 612 patients with high-risk nonmetastatic prostate cancer between 2005 and 2009; of those, 563 were evaluable. They were randomized to receive either androgen suppression plus radiotherapy (281 patients) or that regimen along with chemotherapy (282 patients). The results were published in the Journal of Clinical Oncology.
The median age in the study was 66 years, and most of the patients were white (87.6%). The median prostate-specific antigen (PSA) level was 15 ng/mL, and most patients had a Zubrod performance status of 0 (91.5%). The baseline characteristics were well balanced between the two groups, and the median follow-up period was 5.7 years for the full cohort and 6.1 years for the 461 surviving patients.
The 4-year overall survival rate was 93.3% with chemotherapy and 88.7% without it; at 6 years, these rates were 86.0% and 80.6%, respectively. The hazard ratio (HR) for overall survival was 0.69 (95% CI, 0.49–0.97; P = .034); the P value did not reach a prespecified criterion, though it was below the 0.05 value used for statistical significance. A per-protocol analysis of patients who received the full treatment revealed a greater benefit with the addition of chemotherapy.
There were a total of 43 deaths in the chemotherapy arm compared with 59 deaths in the no-chemotherapy group, and there were also fewer deaths resulting from prostate cancer (16 vs 23, respectively).
The 6-year disease-free survival rate was 65.4% with chemotherapy and 54.9% without it (P = .043), and the median disease-free survival period was 8.5 years and 6.9 years, respectively. The cumulative probability of distant metastasis at 6 years was 9.1% in the chemotherapy group and 14.0% in the no-chemotherapy group, for an HR of 0.60 (95% CI, 0.37–0.99; P = .044). The PSA failure–free rates were similar in the 2 groups at 5 years.
The authors wrote that there were “no unexpected toxicity signals” during the trial. Grade 3 and 4 adverse events were reported in 63.8% of the group that received chemotherapy, compared with 22% of those who did not; there were two grade 5 adverse events in the chemotherapy group, including acute respiratory distress syndrome and multiorgan failure.
“Although there are multiple management options, on the basis of the results of this trial, adjuvant chemotherapy with docetaxel can be reasonably discussed with selected men with high-risk localized prostate cancer who are fit for chemotherapy,” the authors concluded.
In an accompanying editorial, Rahul R. Parikh, MD, and Biren Saraiya, MD, of the Rutgers Cancer Institute of New Jersey, wondered whether the findings are statistical anomalies or a “true clinical revelation.” They suggested that a meta-analysis including this and several other similar studies may help answer the question, and noted that developing biomarkers to determine who would benefit from this therapy would help others avoid unnecessary toxicity.
“We truly need to identify the right patient, pathologic, clinical, and molecular features to target the appropriate therapeutic approaches,” they wrote. “In the near future, we likely will see the evolution of the prostate cancer treatment paradigm with biologics and personalized medicine as observed in many other cancers.”