RESPONSE - Re: Quality of Life in Advanced Prostate Cancer: Results of a Randomized Therapeutic Trial
Year: 1999
Type: article
Abstract: Dr. Albertsen voiced concern about our selection of five primary end points for the Southwest Oncology Group (SWOG)-coordinated INT-0105 quality-of-life (QOL) study, noting that three of the five end points addressed known treatment-related side effects. We selected five end points and adjusted the significance levels accordingly to control for type I error. There was no adjustment for multiple testing in Dr. Albertsen's QOL results (discussed below). Two of our outcomes addressed emotional and physical functioning, good surrogates for overall QOL. Our strongest outcome measure, emotional functioning, was not a known side effect of flutamide. At first glance, data from the article by Albertsen et al. (1) cited by Dr. Albertsen appear to contradict emotional functioning findings reported in the INT-0105 randomized trial of orchiectomy plus placebo versus orchiectomy plus flutamide for patients with stage D2 prostate cancer. However, there are a number of important differences between the two studies that make the comparisons extremely difficult, if not meaningless. First, our study was a trial with 737 patients randomized to two different treatments: surgical castration versus surgical castration plus an antiandrogen. Albertsen's study was not a randomized trial and did not include a comparison arm with a castration-only group. All patients received total androgen blockade with medical castration (using a leutinizing hormone-releasing hormone agonist) plus flutamide. Forty-seven percent of the patients in Albertsen's study were classified as “in progression” (hormone-resistant disease); these patients were required to have had 1 month or more of combination therapy. Consistent increases in prostate-specific antigen (PSA) values of 4 ng/mL or more was one of the criteria for disease progression. The SWOG QOL study had no patients with hormone-insensitive disease and did not include PSA levels as a criterion for progression. The second group of patients in Albertsen's study was classified as “in remission” (stable disease), with 3 months or more of combination therapy; these patients had PSA values of less than 4 ng/mL. Therefore, it is difficult to compare QOL outcomes for the patients in Albertsen's study to those in the INT-0105 patient sample. It is possible that both of the patient groups studied by Albertsen et al. represent better clinical status than the INT-0105 group. Finally, Albertsen's comments suggest that patients in his study were assessed considerably beyond the primary treatment phase, but the authors did not report average duration of total androgen blockade therapy for the two patient groups. This is important because we did not see statistically significant differences (with a stringent significance level of .003, adjusted for multiple comparisons) until months 3 and 6 after patients were randomly assigned to treatment. In the SWOG trial, both treatment arms demonstrated improvement in the Mental Health Index scores (the same measure used in Albertsen's study) over the 6-month period, but patients treated with orchiectomy alone showed significantly more improvement.
Author: C. M. Moinpour
Institution: Fred Hutch Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2787637204