Sexuality in metastatic prostate cancer What can we do to improve patients’ quality of life during ADT treatment?
+m population is highly heterogeneous [5]. As this holds true, the quality of life (QoL) of +m PCa patients remains pivotal [6]. As such, sexual dysfunction (e.g., lower sexual desire (LSD), erectile dysfunction (ED), anejaculation and ejaculatory disorders, lack of orgasmic function, etc.) are listed among the most distressful and bothersome dysfunctions in men treated for +m PCa [6]. The early institution of ADT (any type) in men with +m PCa should be well balanced against the sex-related side effects and long-term morbidity. Equally relevant, the impact of ADT on bone events, cognitive function, and QoL have been appreciated and reported. Published evidence: clinical and pre-clinical Compelling evidence has accumulated over the years with nine currently published studies, specifically evaluating the impact of ADT and sexual function impairment among men with PCa [7–16]. In a recently published study by Corona et al, when combing these studies, it has been demonstrated that ADT resulted in a five to six-fold increased risk of reduced libido and in a three-fold increased risk of developing ED [17]. Reported data on ED were confirmed even when those studies using healthy subjects as a control group were excluded from the analysis (risk for ED = 3.08 [1.96; 4.82]; p < 0.0001) or when only case–control studies were considered (risk for ED = 2.57 [1.71; 3.85]; p < 0.0001). Finally, the risk was higher when studies lasting less than 52 weeks were compared to longer trials (ED risk 3.36 [2.56; 7.40] vs. 2.22 [1.68; 2.92]; Q = 4.90, p = 0.03) [17]. In line with these data, the European Male Aging Study (EMAS), a population-based survey performed on more than 3,400 men recruited from eight European centres, clearly demonstrated that LSD along with ED and reduced morning erections, were the most sensitive and specific symptoms in identifying hypogonadal aging men [18]. Similar results were reported in other large cohorts (n = 4890) of subjects seeking first medical help for ED
or in the Testosterone Trials, a survey performed in up to 800 community-dwelling men recruited from 12 sites in the USA [19,20]. The increased risk of ED after ADT confirms the available pre-clinical data regarding the interconnection between circulating testosterone levels and ED pathophysiology. In this context, the androgen receptor signalling is a pivotal step for penile erections. "Educational and sex-oriented approaches are essential steps for guaranteeing the best outcomes in almost every sexual problem." Accordingly, data has documented that androgens modulate nearly every pathway involved in regulating penile erection at a local level [21]. In particular, androgens are critical for maintaining the right balance between trabecular smooth muscle and connective tissue [22,23]. Moreover, the interconnection between testosterone per se and nitric oxide (NO) pathway is well-established. Likewise, testosterone is involved in the negative control of Ras homolog gene which contains its intrinsic kinase pathway; this strictly regulates the phenomenon of penile detumescence [22,23]. Lastly, androgens are also involved in the regulation of α1-adrenergic responsiveness of smooth muscle cells resulting in increased sympathetic cavernosal smooth muscle tone [22]. Patient counselling Educational and sex-oriented approaches are essential steps for guaranteeing the best outcomes in almost every sexual problem [24–26]. This is particularly true in men with PCa undergoing ADT, where multiple problems can influence couple fitness [6]. Body feminisation including gynecomastia, hot flushes, loss of muscle mass,
and genital shrinkage, along with sexual dysfunction and mood disturbances, can
Prof. Andrea Salonia Experimental Oncology/Unit of Urology, IRCCS Ospedale San Raffaele; Vita-Salute
profoundly affect patient and partner self-esteem and psychological well-being [27]. This is even more relevant in +m PCa, with an incredible number of psychologic rebounds. Therefore, correct patient management can be achieved through collaboration with GPs, psychologists, sexologists, uro-andrologists and medical oncologists. In this context, patients and partners need to be counselled and informed. Open and correct communication is pivotal for the management of couples’ expectations along with patient’s personal experience. Couples should be exhaustively informed that the orgasm sensation could be still experienced, even in the absence of firm erections, so that penetrative intercourse is not considered essential to remaining sexually active. In the presence or not of firm erections, patients and their partners should be informed that ADT increases the threshold for triggering the orgasm experience, so a more intense sexual stimulation over a longer period is required [17]. An adequate educational program and intervention is beneficial to mitigate the decline in sexual intimacy in men undergoing ADT and may allow couples to maintain more successful and satisfactory intimate and emotional relationships, thus including sexual activity. Finally, the inclusion and empowerment of a partner – whenever actually present – throughout the educational process could enhance outcomes and continuation of sexual activity, even in +m PCa individuals.
San Raffaele University (IT)
salonia.andrea@hsr.it
Dr. Edoardo Pozzi Experimental Oncology/Unit of Urology, IRCCS Ospedale San Raffaele;Vita-Salute
San Raffaele University (IT)
Prostate cancer (PCa) is the most common urological cancer and accounts for nearly a quarter of all new cancers in men [1]. Since the widespread use of prostate-specific antigen (PSA) testing in the 1990s, the incidence of PCa has risen sharply [1,2]. All areas of PCa from diagnosis through to surgical and medical treatments are rapidly advancing. Besides ongoing evaluation of novel biomarkers and genetic profiling, ground-breaking advances in MRI imaging, biopsy techniques, prostatectomy techniques (thus including every type of robot- assisted radical prostatectomy), imaging-guided radiotherapy, and multiple large-scale clinical trials of new drugs within the last decades have made PCa a more and more approachable disease, with better prognosis even at metastatic (+m) stages [1,3,4]. In this context, the median survival of patients with newly diagnosed metastatic PCa is approximately 42 months with ADT alone, being highly variable as
References can be requested from the corresponding authors.
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European Urology Today
February/March 2023
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