Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function

The quality of life of men with prostate cancer is receiving increasing attention and, acknowledging that endocrine therapy conceptually remains a palliative treatment, many patients view the preservation of quality of life to be an equally important goal of therapy as the prolongation of survival [1]. The issue of quality of life is further emphasized by moves to initiate endocrine therapy earlier in the course of the disease and in younger men. Sexuality is an important aspect of quality of life, particularly in middle-aged men but also for most elderly men [2,3]. However, loss of libido and erectile dysfunction (ED) are frequent sequelae of the diagnosis and treatment of prostate cancer [4,5]. Among 401 men with prostate cancer, 71% experienced a loss of libido after surgery or medication (prostatectomy, radiotherapy, hormonal therapy with goserelin, buserelin or leuprolide alone, or in combination with ̄utamide, bicalutamide or nilutamide, and orchidectomy) and overall, about twothirds of those questioned would have preferred their level of sexual activity to be higher [5]. Indeed, sexual functioning is suf®ciently important to some older men that, if they were diagnosed with prostate cancer, they would trade some reduction in survival time for maintained sexual function. In a sample of 50 men (mean age 58 years), 68% were willing to exchange a o10% advantage in 5-year survival to maintain sexual potency [6]. Likewise, Mazur and Hickman [7] found that of 230 men (mean age 65 years), 67% would trade a 14% survival advantage to prevent impotence, while Helgason et al. [4] found that only 38% of a group of 299 men would unconditionally accept a treatment with a 50% risk of impotence. Sexual interest, often referred to as sexual desire or sexual drive, is dif®cult to de®ne [8] and we have not been able to ®nd a precise de®nition in the sexological literature. In recent studies investigating the use of the nonsteroidal antiandrogen bicalutamide (Casodex@, AstraZeneca, UK) in prostate cancer, sexual interest was assessed in a validated quality-of-life questionnaire [9] by scoring the response to three questions addressing `interest in sex', `if the patient felt sexually attractive', and ®nally `whether others ®nd the patient sexually attractive' [10±15]. The decline in sexual interest and activity in patients with prostate cancer may be caused by a multiplicity of factors including the psychological impact of the diagnosis, the disease itself and its treatment [5]. In advanced prostate cancer, androgen deprivation is the mainstay of treatment, and has traditionally been achieved by either medical or surgical castration alone, or in some cases combined with an antiandrogen, as combined androgen blockade (CAB). Both these approaches to treatment are associated with a loss of libido and erectile capability in >80% of patients [5,16±19]. In men for whom their sexuality is important, a decrease in sexual interest and/or erectile capability can result in psychological distress, dif®culties with relationships and loss of self-esteem [5]. Indeed, Helgason et al. [4] found that the decline in sexual function (including sexual desire, erectile capacity and orgasmic pleasure) was the most common cause of disease-related stress in men with prostate cancer. While ED can be treated effectively [20,21], there are no recognized effective therapies for loss of sexual interest [21]. However, in the absence of sexual interest, the treatment of sexual dysfunction becomes less relevant and therefore hormonal treatments for advanced prostate cancer which spare sexual interest are needed. Monotherapy with a nonsteroidal antiandrogen is an emerging treatment option for men with prostate cancer Accepted for publication 11 October 2000 BJU International (2001), 87, 47±56