Hormonal manipulations with chemotherapy

In the analysis of three randomized trials (3,206 men), the HRdeath associated with the addition of docetaxel to standard of care was 0.77 (95% CI, 0.68–0.87; P < .0001), representing an absolute improvement of 9% in 4-year survival (95% CI, 5–14).[43][Level of evidence A1]

In the CHAARTED trial (NCT00309985), 790 patients with metastatic, hormone-sensitive disease were randomly assigned to receive ADT with or without docetaxel (75 mg/m2 intravenously [IV] every 3 weeks for 6 cycles).[44,45] Previous adjuvant ADT was permissible if it lasted 12 months or less and progression had occurred within 12 months of completion. Patients were prospectively stratified as having a high- versus low-volume disease, with high volume defined as presence of visceral metastases or at least four bone lesions, with at least one lying outside the vertebral column or pelvis. About 65% of patients had high-volume disease by this definition.

In the CHAARTED trial (NCT00309985), 790 patients with metastatic, hormone-sensitive disease were randomly assigned to receive ADT with or without docetaxel (75 mg/m2 intravenously [IV] every 3 weeks for 6 cycles).[44,45] Previous adjuvant ADT was permissible if it lasted 12 months or less and progression had occurred within 12 months of completion. Patients were prospectively stratified as having a high- versus low-volume disease, with high volume defined as presence of visceral metastases or at least four bone lesions, with at least one lying outside the vertebral column or pelvis. About 65% of patients had high-volume disease by this definition.

With a median follow-up of 53.7 months, median OS in the ADT-plus-docetaxel arm was 57.6 months and in the ADT-alone arm, it was 47.2 months (HRdeath, 0.72; 95% CI, 0.59–0.89; P = .0018).[45][Level of evidence A1]

In the CHAARTED trial (NCT00309985), 790 patients with metastatic, hormone-sensitive disease were randomly assigned to receive ADT with or without docetaxel (75 mg/m2 intravenously [IV] every 3 weeks for 6 cycles).[44,45] Previous adjuvant ADT was permissible if it lasted 12 months or less and progression had occurred within 12 months of completion. Patients were prospectively stratified as having a high- versus low-volume disease, with high volume defined as presence of visceral metastases or at least four bone lesions, with at least one lying outside the vertebral column or pelvis. About 65% of patients had high-volume disease by this definition.

The survival advantage was observed only in patients with high-volume disease. In the group with high-volume disease, there was a clear improvement in median OS (61.2 months vs. 34.4 months) (HR, 0.63; 95% CI, 0.50–0.79; P < .001). However, there was no observed difference in survival in men with low-volume disease (median OS, 63.5 months vs. not reached) (HR, 1.04; 95% CI, 0.70–1.55; P = .86). The test for heterogeneity of efficacy was statistically significant (P = .033).

In the CHAARTED trial (NCT00309985), 790 patients with metastatic, hormone-sensitive disease were randomly assigned to receive ADT with or without docetaxel (75 mg/m2 intravenously [IV] every 3 weeks for 6 cycles).[44,45] Previous adjuvant ADT was permissible if it lasted 12 months or less and progression had occurred within 12 months of completion. Patients were prospectively stratified as having a high- versus low-volume disease, with high volume defined as presence of visceral metastases or at least four bone lesions, with at least one lying outside the vertebral column or pelvis. About 65% of patients had high-volume disease by this definition.

Comparison of QOL between the two study groups, as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale, was not found to exceed the prospectively defined minimally important difference at any time point over the 12 months of planned assessment.[46]