Outcomes beyond tumor response and patient survival have increasingly gained in importance over the past two decades. Quality of life (QOL) and cost-effectiveness of therapy have emerged as additional end points of interest. Conflicting results can and have been reported, however, depending on the measures used to report QOL and cost-effectiveness. Examples of QOL and cost-effectiveness issues and measures related to androgen deprivation therapy (ADT) for prostate cancer follow. [Oncol News Int 6(Suppl 3):22-24, 1997]
ABSTRACT: Outcomes beyond tumor response and patient survival have increasingly gained in importance over the past two decades. Quality of life (QOL) and cost-effectiveness of therapy have emerged as additional end points of interest. Conflicting results can and have been reported, however, depending on the measures used to report QOL and cost-effectiveness. Examples of QOL and cost-effectiveness issues and measures related to androgen deprivation therapy (ADT) for prostate cancer follow. [Oncol News Int 6(Suppl 3):22-24, 1997]
Potency and other measurements of sexual function were significantly inferior among men with prostate cancer treated with radiation plus androgen deprivation therapy than among men treated with radiation alone, according to a small pilot study conducted at Fox Chase Cancer Center. The results of that study were reported by Deborah Watkins Bruner, RN, MS, at the First Sonoma Conference on Prostate Cancer. Ms. Bruner, a PhD candidate at the University of Pennsylvania, is Director of the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center.
The purpose of the study was to assess sexual function after definitive radiotherapy (RT) with or without androgen deprivation therapy (ADT) in younger men (aged 50 to 65). The Sexual Adjustment Questionnaire was used to assess sexual function in five areas: desire, arousal, orgasm, frequency, and satisfaction (Reference: Nicolaou N, Bruner DW, Hanks G, et al: Sexual function after radiotherapy +/- androgen deprivation for clinically localized prostate cancer in younger men (age 50 - 65) [Abs] Int J Radiat Oncol, Biol, Phys 36(1) (Suppl), 1996.)
The RT/ADT group was found to be significantly inferior to both the RT only and the control group in all areas of sexual function measured, as would have been expected. Somewhat suprising, however, is that the men no longer on ADT did not return to the sexual functioning levels of men who received radiation only. The RT only group was significantly inferior to the control group regarding sexual arousal, function, and frequency, but not in desire or satisfaction. The mean follow-up was 2.6 years.
Data analysis showed these rates of potencydefined as erection sufficient for sexual intercourse:
Ms. Bruner reminded the conference participants that pretreatment potency was on a recall basis. Were asking them after the fact. ...The men...and there were only 22 of them...who had androgen deprivation therapy, reported 100% potency pretreatment. So, I think theres some recall bias.
Potency results of the RT only group compared favorably with previously published reports for radiotherapy and were better than rates after radical prostatectomy. Potency rates for RT/ADT were similar to previous reports.
Of the 98 men treated with radiotherapy, with or without androgen deprivation, 67 (68%) returned the questionnaire. Of those 45 had radiation only. So we have a very small group here who had androgen deprivation therapy, Ms. Bruner said. Among the 142 matched controls who agreed to participate, 48 (34%) actually completed the forms.
I think the contribution of this pilot study was looking at the age-matched controls, Ms. Bruner said. We need to know more about what is normal sexual function by age group to assess the true magnitude of change due to therapy. Some previous quality of life studies, she noted, compared younger to older men. And thats quite a problem, she said, because we know that men lose potency over time, with age.
Some conference participants expressed concern that the study results were not correlated with testosterone levels. Before you can think about recovery of libido you need to know that testosterone has recovered, stated Mitchell Benson, MD, Professor of Urology at Columbia University. He said that he had been checking testosterone levels in all of his patients receiving intermittent hormone therapy and that testosterone level is very much a function of how long they were on their androgen deprivation.
Dr. Benson said that his patients receiving short-term ADT have bounced back within months. Now, they may not come back to the same level that they wereI mean they may have some permanent diminution in total testosterone, but they always come back. For patients on long-term therapy, however, there appears to be some permanent testicular damage.
Ms. Bruner pointed out the difficulty in measuring testosterone. The problem is, at least in the large trials, that there are many different assays for testosterone and many ways of reporting. In addition, we dont know when the testosterone was drawn and levels change with circadian rhythms
One of the interesting things about the sexual adjustment questionnaire, Ms. Bruner said, referring to the Fox Chase study, is that there is a question that asks men: Do you think that cancer impacted your sexual relationship? And then the second question is: Do you think the treatment affected your sexual relationship? I honestly thought, when I read that, they would not be able to differentiate, but they can. They were clearly able to differentiate between the cancer affecting their relationship and the treatment, Ms. Bruner stated. And the treatment, they felt, was worse than the cancer with regard to sexual function, which is frightening.
Ms. Bruner also discussed another of the quality of life end points, the Q-twist, which stands for quality-adjusted time without symptoms and toxicities.
A study by the European Organization for Research and Treatment of Cancer analyzed quality-adjusted survival comparing maximal androgen blockade with orchiectomy in patients with metastatic prostate cancer. Q-twist methodology was used to obtain summary measurement of the trade-off time between the side effects of treatment (hot flashes and gynecomastia), time to progression, and duration of survival. And what they found was that with the quality adjustment, androgen blockade ended up better than orchiectomy alone. There was a 5.2 month difference in favor of the androgen blockade40.6 months of quality-adjusted survival, versus 35.4 months for orchiectomy. (Reference: Rosendahl KJ, et al: A quality-adjusted survival (Q-Twist) analysis of EORTC trial 30853 comparing maximal androgen blockade (MAB) with orchiectomy in patients with metastatic prostate cancer [Abs]. Proc Am Soc Clin Oncol, J Clin Oncol 16: 1997.)
Ms. Bruner found the results interesting but criticized the methodology. Normally in a Q-twist, a quality adjustment is done by a panel of experts, she said, which is probably the biggest problem with the Q-twist...In prostate cancer, there probably really isnt much of a place for a Q-twist. In a disease where the patient can answer quality of life questions themselves, I cant really understand why we would need to use a panel of four experts to decide the quality of life of men who can speak for themselves. Q-twist is probably more applicable in brain or lung, she said, where patients are not always able to answer quality of life questions as they become sicker.
Another end point of increasing interest is cost-effectiveness. In a study comparing surgical orchiectomy with LHRH analogues, to surgical orchiectomy plus flutamide (Eulexin), flutamide increased average survival by 5.2 months at an incremental cost of $25,300 per life year gained. The study did not, however, adjust for quality of life. (Reference: Hillner BE, et al: Estimating the cost effectiveness of total androgen blockade with flutamide in M1 prostate cancer. Urology 45(4):633-640, 1995.)
Ms. Bruner was encouraged by the conference presentations on models to predict which men have cancers that are less likely to recur. If we could, from certain prognostic factors, figure out which men are less likely to recur, they would be the ones that you might really want to target in regard to information about some of these quality of life trade-offs, or interventions to improve quality of life she said.
Ms. Bruner stated that a problem with many quality of life studies, is that often the minimally potent are lumped in with the fully potent, giving a positive spin on the data. What is strongly needed is a clear and standardized definition of potency.
In addition to defining potency, identifying what the pertinent quality of life and cost-effectiveness issues are by age, stage, and therapy for prostate cancer, defining the concept, and choosing appropriate measures and models for analysis remain challenges for the future.