Sexual and urinary morbidities resulting from treatment of pelvic malignancies are common. These treatment sequelae are significantly bothersome to patients and challenging to address. Awareness of these complications is critical in order to properly counsel patients regarding potential side effects and to facilitate prompt diagnosis and management. Addressing these issues often necessitates a coordinated multidisciplinary approach; however, the effort required often translates into improvement in patient quality of life. Herein we review the sexual and urinary side effects that may arise during or after treatment of pelvic malignancies.
Urinary and Sexual Complications Associated With Chemotherapy and Hormonal Therapy
Urinary complications associated with chemotherapy have been well documented, especially in pediatric populations in whom high doses of chemotherapeutic agents, particularly cyclophosphamide and ifosfamide, have been extensively studied. The most common and severe urinary complication is hemorrhagic cystitis, which can vary from relatively asymptomatic microscopic hematuria to life-threatening hemorrhage. In a large retrospective series from St. Jude Children’s Research Hospital, several risk factors for grade 3 or higher hemorrhagic cystitis were identified, including pelvic RT, bone marrow transplantation, BK virus positivity, acute lymphocytic leukemia, cyclophosphamide exposure, and male sex. The cause of hemorrhagic cystitis resulting from treatment with cyclophosphamide or ifosfamide is believed to be the conversion of cyclophosphamide or ifosfamide to urotoxic metabolites, such as acrolein. Mesna is an organosulfur frequently administered with alkylating agents to assist in detoxifying their metabolites via reaction of its sulfhydryl group with α,β-unsaturated carbonyl-containing compounds such as acrolein. Other anti-inflammatory agents have also demonstrated effectiveness in decreasing the severity of hemorrhagic cystitis in preclinical models, including ketamine and interleukin-1 receptor antagonists.[59,60] This is obviously an area where the value of prophylactic treatment is well established. However, early recognition of the signs of this toxicity (eg, microscopic hematuria) and discontinuation of treatment for progressive symptoms are critical to its successful management.
Sexual dysfunction associated with chemotherapy is common and likely underreported in the literature. Premature ovarian failure is a common consequence of chemotherapy in reproductive-age women, and, as a result, fertility issues and sexual dysfunction occur frequently in women who have undergone chemotherapy. Sexual dysfunction associated with estrogen withdrawal and psychological stress is also widespread in female cancer survivors. Women who suffer from sexual dysfunction may benefit from counseling and targeted interventions. A recent Cochrane review of the literature evaluated several clinical trials looking at psychoeducational interventions, as well as pharmaceutical interventions and pelvic floor exercise, but failed to definitively identify a pattern of benefit associated with any of these interventions.
Sexual dysfunction in men is related to chemotherapy primarily when the agents used cause hypogonadism. Chemotherapy-induced hypogonadism is well documented with several agents, especially alkylating agents, and is more common in patients with renal disease and in those undergoing treatment for Hodgkin lymphoma; it may be proportional to gonadal activity. It remains unclear whether gonadal quiescence during chemotherapy is protective.
ADT, by definition, lowers testosterone and commonly results in loss of libido and erectile dysfunction. While these side effects are expected during therapy, recovery once androgen suppression is discontinued can be variable. Recognizing the signs and symptoms associated with an ongoing hypogonadal state is the first step in identifying the problem. In many cases, the side effects are transient and men recover once the therapy is complete; however, chronic symptoms associated with low levels of testosterone persisting for 12 months or longer after completion of therapy may be an indication for testosterone supplementation. This complication is likely underappreciated by many cancer survivors, who end up suffering from a treatable condition.
Overview of Treatment of Urinary and Sexual Complications in Cancer Survivors
In general, cancer survivors experiencing urinary side effects are bothered by symptoms of urinary incontinence, urinary retention, bladder overactivity, hematuria, and/or bladder pain. These symptoms may be isolated or overlapping, making treatment challenging to physicians—and confusing and frustrating to patients.
- After cancer treatment, patients report difficulty adjusting to changes in physical appearance, daily functioning, and social roles.
- Urinary and sexual dysfunction are common and burdensome sequelae of treatment of pelvic malignancies.
- Numerous pharmacologic and surgical therapies exist to address urinary and sexual dysfunction that can follow treatment of pelvic malignancies.
- Recognition of the sequelae of oncologic treatment allows for early intervention and subsequent improvement in the quality of life of cancer survivors.
In men with urinary incontinence, an assessment of the driving cause of their incontinence is critical if the practitioner is to provide adequate counseling regarding management options. Stress incontinence can be managed, after a detailed urologic evaluation, with PFMT, a transobturator urethral sling, or an artificial urinary sphincter.[65,66] These interventions have been shown to improve overall QOL in these patients, as in the patient in Case 1. Women with stress urinary incontinence after treatment of a gynecologic malignancy should be evaluated for fistulous disease or cancer recurrence. In the absence of an ominous finding, surgical treatment with a midurethral sling, retropubic colposuspension, or injection of bulking agents is feasible. The choice of approach is driven by the effect of the incontinence on the patient’s QOL, the severity of leakage, and the degree of lower urinary tract dysfunction.
Urinary frequency, urgency, and nocturia classically are considered irritative lower urinary tract symptoms secondary to bladder overactivity. These changes may occur after either an insult to bladder mucosa or bladder innervation. Surgery, chemotherapy, and RT can all lead to bothersome irritative urinary tract symptoms. Such symptoms may respond to dietary modifications (avoiding bladder irritants), antimuscarinic drugs, treatment with a β3 agonist, onabotulinum toxin A intravesical injections, or neuromodulation. When these therapies are exhausted, urinary diversion may be indicated in very-well-selected patients—such as the woman in Case 2.
Urinary retention after pelvic surgery may present as overflow incontinence or frank retention. In this setting, appropriate bladder drainage is necessary. Urethral catheterization is reasonable in the acute setting; however, urethral catheterization or suprapubic catheterization is not an appropriate long-term form of bladder management and is discouraged. Clean intermittent catheterization carries a lower risk of urinary tract infection, allows more flexibility in daily activities, and is a safe mode of bladder management in patients who are able to reliably self-catheterize or who have an adequate support structure to assist with catheterization.
Erectile dysfunction is commonly seen in men treated for pelvic malignancies. Erectile dysfunction is normally managed initially with phosphodiesterase type 5 (PDE5) inhibitors. PDE5 inhibitors are excellent treatments for erectile dysfunction resulting from RT.[67-69] A recent survey of erectile function in prostate cancer patients treated with hormonal therapy and IMRT showed that PDE5 inhibitors provided satisfactory response in 66% of men using the medications. Additional therapies include vacuum erection devices, intraurethral alprostadil suppositories, intracavernosal injections (papaverine, phentolamine, alprostadil), and penile prostheses. All of these modalities have been shown to improve QOL in patients with erectile dysfunction.
Sexual dysfunction may be present in both men and women with pelvic malignancies. The interplay between physical, psychological, and social factors influences sexual desire, libido, and satisfaction. Therapists specializing in psychosexual care can help address the psychological and social component of sexual dysfunction at the same time that medical and surgical therapies are being used to address the biological facets of the problem. This is an area where a great need for additional support has been identified. However, this need is not yet well addressed in the comprehensive care of cancer survivors.
Exercise and Physiotherapy in the Management of Urinary and Sexual Dysfunction Resulting From Treatment of Pelvic Malignancies
Exercise and physiotherapy are of interest for management of both urinary and sexual dysfunction after treatment of pelvic malignancies because many of the etiologies of these dysfunctions are physical in nature. Making maximal use of exercise and physiotherapy has numerous advantages, including improvement in other comorbid conditions, overall well-being, low cost, ease of implementation, and relatively few side effects.
Data supporting exercise or physiotherapy as interventions in sexual dysfunction are limited. A recent Cochrane review identified 11 contemporary randomized controlled trials that assessed the effectiveness of treatments for sexual dysfunction resulting from cancer treatment in women. Only one of the trials evaluated the effect of exercise on sexual function. Of 34 patients with gynecologic cancers and pelvic floor dysfunction following radical hysterectomy and pelvic lymph node dissection, 24 completed a 4-week pelvic floor rehabilitation program (PFRP) or usual care. Outcomes included pelvic floor dysfunction (as measured by the pelvic floor dysfunction questionnaire), pelvic floor muscle strength, motor-evoked potential of the sacral nerve, and patient-reported health-related QOL. At 4 weeks, there were improvements in the PFRP group in pelvic floor strength and sexual functioning, as well as QOL. However, the systematic review concluded that the evidence that pelvic floor exercise improves sexual function is weak.
In men, the evidence for the impact of exercise or physiotherapy is most abundant by far in prostate cancer patients. One trial randomized men post radical prostatectomy to usual care or exercise for 6 months. While improvements in measures of physical fitness were found in the exercise group, exercise had no impact on recovery of erectile function. Recently, higher levels of physical activity have been correlated with better erectile and sexual function in men treated for prostate cancer.Overall, given the likely favorable risk-benefit ratio, PFRP for women and exercise for men with sexual dysfunction seem reasonable.
There is somewhat stronger evidence that physiotherapy may improve urinary incontinence in patients following treatment of pelvic malignancies. In the case of stress incontinence, the chief culprit appears to be pelvic floor weakness. Although an earlier systematic review concluded that PFMT for the treatment of urinary incontinence after radical prostatectomy hastens the return to continence, a more recent systematic review concluded that the benefit of conservative measures is uncertain.[74,75] The authors of the more recent review did, however, note moderate evidence of an overall benefit from PFMT vs no PFMT in reduction of urinary incontinence.
Physiotherapy in survivors of gynecologic cancers may increase recovery of urinary function. A small pilot randomized controlled trial (N = 40) in which the majority of patients had uterine cancer (60%) and were treated with multimodality therapy (RT, 18%; surgery, 95%; chemotherapy, 35%) randomly assigned patients to 12 weeks of PFMT plus behavioral therapy or to usual care. After 12 weeks, the PFMT group had significantly improved urinary continence. Of note, a Cochrane review found that there is evidence of widespread recommendation of PFMT for women without cancer who have stress or any other type of urinary incontinence. Overall, given this evidence, PFMT seems reasonable as conservative treatment of urinary incontinence, particularly anatomic or stress incontinence, in patients with a history of treatment of a pelvic malignancy.
The management of pelvic malignancies with surgery, chemotherapy, and RT is complicated by the prevalent urinary and sexual side effects that affect long-term patient QOL. Recognition of possible problems with urinary function, such as urge or stress incontinence or hemorrhagic cystitis, is critical if practitioners are to adequately counsel patients and manage their posttreatment course. Similarly, sexual dysfunction—including dyspareunia, vaginal shortening/stenosis, sensory loss, erectile dysfunction, and ejaculatory dysfunction—affects patients psychologically and socially. Having a clear understanding of the sequelae of treatment of pelvic malignancies allows for clinical recognition and improvement in health-related QOL outcomes.
Financial Disclosure: Dr. Peterson is a consultant for American Medical Systems/Boston Scientific. Boston Scientific provides an educational grant for the reconstructive urology fellowship at Duke University Medical Center. The other authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
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