Bladder cancer ranks the fourth most common cancer in men and ninth in women in the United States, accounting for an estimated 70,980 new cases in 2009.[1] [Jemal A, Siegel R, Ward E, et al. CA Cancer J Clin. 2009; 59: 225-49] Because women may go through more extensive diagnostic procedures to rule out competing diagnoses such as endometrial cancer, they may experience a delay in diagnosis.[2][ Johnson EK, Daignault S, Zhang Y, et al. Urology. Sep 2008; 72(3):498-502] As such, their treatment often entails greater morbidity than that among men, including the use of radical cystectomy.[3] [Cardenas-Turanzas M, Cooksley C, Pettaway C, et al. Obstetrics & Gynecology. July 2006; 108(1):169-175]
Treatment of bladder cancer is dependent on the degree of cancer involvement. Superficial bladder cancer is confined to the innermost two layers of bladder tissue and can be treated simply with cystoscopic removal (transurethral resection) or laser ablation, followed by Bacillus Calmette-Guérin (BCG) immunotherapy in the bladder. Though they are both easy to detect and resect, recurrence rates are high at up to 70%, with progress in stage or grade in up to 15%.[4] [Allard P, Bernard P, Fradet Y, et al. Br J Urol.1998; 81: 692–8]. Consequently, patients treated for non-invasive urothelial tumors must undergo intensive surveillance with cystoscopy.
Tumors that progress into the smooth muscle of the bladder are considered invasive. Invasive cancers that are confined to the pelvis require radical cystectomy with lymph node dissection. In cases requiring cystectomy, urinary diversions create a channel for urine drainage to the skin using a small segment of the small intestine. For women radical cystectomy is also referred to as anterior pelvic exenteration with urinary diversion. The procedure entails bilateral pelvic lymphadenectomy, cystectomy, urethrectomy, hysterectomy, salpingo-oophorectomy, and partial anterior vaginectomy. Patients at risk of requiring cystectomy due to invasive bladder cancer are generally older; late stage diagnoses have been recorded among 54% compared to 23% among younger patients.[5] [Yossepowitch O, Dalbagni G. J Urol. 2002; 168:61–66.]
Patients eligible for bladder-sparing surgery may receive radiosensitizing chemotherapy, followed by a course of radiation to the pelvic lymph nodes and bladder. Neoadjuvant chemotherapy such as the use of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), has been used to prolong survival in advanced cancers.[6] [ Advanced Bladder Cancer Meta-Analysis Collaboration. Lancet. 2003; 361(9373): 1927-34.]
With more effective treatments available, more bladder cancer patients are surviving longer. Thus, treatments need to focus more upon quality of life of the cancer survivor as much as it does on cure. Still, there is an unfortunate paucity of research on the effects of such treatments on female sexual function.
Among urological and gynecological procedures, cystoscopy is regarded as minimally invasive, however the procedure can still be unpleasant for the patient and when repeated multiple times may be associated with sexual side effects infrequently recognized by clinicians. One study of quality of life before and after cystoscopy reported impaired sexual function two weeks after the procedure among more than 75% of the sample population; 50% of women in the study reported a decrease in libido. Fortunately, these findings returned to baseline after one month.[7] [Stav K, Leibovici D, Goren E, et al. Israel Med Association Journal. Aug 2004; 6: 474-478.] In another study of patients under surveillance for recurrence after treatment of superficial bladder cancer, 78% of female patients reported some form of vaginal dysfunction, including difficulty with vaginal lubrication. This study could not determine whether the dysfunction was a result of cystoscopy or the anxiety resulting from the patient’s surveillance status. The study also found that 23% of sexually active patients in the study were afraid of harming or contaminating their partner with sexual contact during this period. This fear was significantly less prevalent among patients receiving intravesical BCG, indicating that extent of cancer control may play a large role in sexual dysfunction. [8] [Van der Aa, MN, Bekker MD, Van der Kwast TH, et al. BJU International. 2009; 104: 35–40]
As intravesical therapy with BCG causes an inflammatory reaction within the bladder with the intent of controlling growth of any abnormal tumor cells, its use is associated with symptoms such as dysuria, frequency, and bladder spasms. No studies currently exist on sexual function following intravesical therapy; only rare case reports of complications affecting men exist, including those of balanitis, epididymitis, and orchitis. No reports of genital infection/inflammation related to the therapy have been encountered in women.[9] [Erol A, Ozgur S, Tahtali N, et al. International Urology and Neprhology. 1995; 27 (3): 307-310] [10] [Sofienberg Harving S, Asmussen L, Roosen JU, et al. Scandinavian Journal of Urology and Nephrology. Sep 2009; 43(4):331 – 333]
Most of the literature on sexual dysfunction as it relates to invasive bladder cancer is unfortunately focused on male patients and radical cystectomy as treatment. Removal of the bladder and urethra may damage the neurovascular bundles of the vagina, as well as devascularize the clitoris, all of which affect sexual arousal, desire, and satisfaction.[11] [Schoenberg M, Hortopan S, Schlossberg L, et al, J Urol. 1999; 161: 569–572] Resection of the proximal two thirds of the vagina, as needed in cases of tumor involvement in the bladder neck, results in transection of the autonomic nerves to the vagina affecting lubrication. Though female pelvic exenteration is associated with significant sexual morbidity, simple cystectomy itself has been associated with sexual dysfunction. One study in which patients with interstitial cystitis were treated with simple removal of the bladder, without damage to the urethra, vagina, or uterus, found that 29% of patients had experienced significant narrowing of the vaginal canal postoperatively.[12] [Elzevier HW, Nieuwkamer BB, Pelger R, et al. J Sex Med. 2007; 4:406-416]
Furthermore, premenopausal women whose ovaries must be removed experience acute surgical menopause with symptoms of vaginal atrophy and dryness resulting in painful intercourse.[13] [Miranda-Sousa AJ, Davila HH, Lockhard JL, et al. Cancer Control. July 2006; 13(3)] Emotional factors such as a decrease in sexual attractiveness may influence sexual function after surgery as well. One study reported nearly a third of its female bladder cancer patients feeling less sexually attractive after cystectomy, most often due to the need for urinary diversion.[14] [Bjerre BD, Johansen C, Steven K. Scand J Urol Nephrol. 1997; 31:155-160] Partners may experience decreased desire for sexual activity secondary to the patient’s appearance or due to a fear of contamination with the cancer. More conservative treatments and modification of surgical techniques may be associated with improved sexual function.
Retrospective analyses have shown after mean follow-up of 13 months that patients receiving nerve-sparing surgery experience no significant decline in sexual function, indicating that surgical planning can help prevent negative effects on sexual health. Alternatively, patients who did not receive nerve-sparing surgery fared significantly worse, with significant vaginal dryness, lack of arousal, and dyspareunia, leading to discontinuation of sexual intercourse in most patients.[15] [Nandipati KC, Bhat A, Zippe CD. Urology. Jan 2006; 67(1): 185-186] Suggested surgical methods to preserve sexual function include the identification of the neurovascular bundles of the lateral vaginal walls, preservation of the anterior vaginal wall to maintain vaginal lubrication, and reconstruction of the vagina to preserve vaginal depth and pain-free intercourse.[16] [Zippe CD, Raina R, Shah AD, et al. Urology. June 2004; 63(6): 1153-1157] Formal studies of sexual function in patients after receiving these surgical modifications in the long-term should be explored further.
Outside the United States, radical cystectomy is less the standard compared to external beam radiation therapy. Zietman compiles the results of 4 randomized trials from the United States and Europe in which radiation is performed initially as treatment for invasive bladder cancer instead of cystectomy. In these cases, 5 year survival rates and incidence of metastasis were not different with radiation and cystectomy performed as salvage compared to radiation and immediate cystectomy. Further analysis of trimodality therapy (transurethral resection of tumor, chemotherapy, and radiation) was also found by Zietman et al to be comparable to radical cystectomy in 5 year survival. Though recurrence was found more often among those retaining their bladders, their recurrences could be controlled with intravesical BCG. These findings indicate that physicians may consider trimodality therapy with surveillance instead of immediate radical cystectomy, with the option of radical cystectomy as salvage for cases of recurrence or non-complete remission.[17] [Zietman AL, Shipley WU, Kaufman DS. Ann Med. 2000; 32(1): 34-42] Women able to preserve native blader function report no significant decrease in sexual function compared to women undergoing urinary diversion.[18] [Kachnic LA, Shipley WU, Griffin PP, et al. Cancer J Sci Am. 1996; 2: 79–84.] Nevertheless, radiation therapy itself has significant negative impact on sexual function as seen in the literature on sexual dysfunction among female patients treated for vaginal cancers with radiation.
As surgery for invasive bladder cancer has been guided by the need to prevent recurrence, preservation of sexual function has not been well evaluated in research nor put into practice guidelines. However, various institutions have made efforts to modify cystectomy to preserve sexual function, if not indirectly through the preservation of continence. Ileal conduits used for urinary diversion require patients to wear urostomy bags which may leak, produce odor, and irritate skin at the urostomy site, all of which may lead to increased self-consciousness and decreased desire for sexual activity. Some institutions have therefore adopted the creation of orthotopic neobladders in cystectomy patients. Neobladders are created by the reconfiguration of bowel to create a hidden reservoir for urine that is attached to the anterior abdominal bowel wall and can be catheterized for intermittent drainage by the patient. [19] [Hautmann RE, Miller K, Steiner U, et al. J Urol. 1993; 150 (1): 40-5] In some patients whose cancers show no spread to the bladder neck, the urethra can be spared[20] [Stenzl A, Colleselli K, Poisel S, et al. Eur Urol. 1998; 33(S4):18-20.] such that the surrounding clitoral neurovasculature remains undamaged by surgery and so that the neobladder can be connected to a natural point of evacuation. [21] [Horenblas S, Meinhardt W, Ijzerman W, et al. J Urol. 2001;166:837-840] One study comparing sexual function between patients with ileal conduit versus continent orthotopic neobladder diversion found that both groups suffered significant relationship difficulty, decreased libido, and dyspaerunia, however patients with neobladders experienced significantly less dysfunction. Patients with orthotopic neobladders may lead more active and social lifestyles, untethered by urostomy bags and the fear of daytime leakage. Suboptimal outcomes in patients with ileal conduits may be due to decreased performance status at baseline leading to their ineligibility for continent neobladder procedure and more difficult surgical recovery.[22] [Osman Y. El-Bahnasawy M, El-Hefnawy A. Eur Urol Suppl. 2007; 6(2):209] Patients with ileal conduits may also experience skin problems around the stoma and more difficulty managing its care. In general though, both patients may suffer from fear of recurrence, financial worries, family distress, and uncertainty about the future even years after their initial surgery; these problems may be allayed with the prompt attention and guidance of a wound, ostomy, and continence nurse.[23] [Gemmill R, Sun V, Ferrell B, et al. J of Wound, Ostomy and Continence Nursing. Jan/Feb 2010: 37(1):65-72]. Some suggestions for improving sexual encounters for patients with urostomy sites may include the use of fancy slips or underwear with croth cut outs to hide the abdominal urostomy site or an incontinence pad. For patients wearing collection bags, securing the device with tape is advised. Collection bags and neobladders should be emptied before sexual activity. More importantly however, patients should be encouraged to openly discuss their sexuality with their partners so as to create an environment of understanding, rather than anxiety from fear of unmet expectations.[24][Weerakoon P. Sexualitiy and Disability. Summer 2001; 19(2):121-9.] Looking forward, patients with urinary diversion may also benefit from at least 60 minutes of strenuous exercise each week, shown to increase sexual interest in women. Exercise increases blood flow and circulation of testosterone; the release of endorphins may also improve self-efficacy, self-esteem, and mood states. Exercise also has been shown to improve body image in these patients, perhaps mitigating the effect of urinary diversion and scarring on sexual function.[25] [Karvinen KH, Courneya KS, North S, et al. Cancer Epidemiology, Biomarkers, and Prevention. May 2007; 16:984]