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How Can We Effectively Address the Medical and Psychological Concerns of Survivors of Pelvic Malignancies?

How Can We Effectively Address the Medical and Psychological Concerns of Survivors of Pelvic Malignancies?

Oncology (Williston Park). 31(4):268-294.
Table 1. Continence Rates Following RRP, RPP, and RALP
Table 2. Incidence of Grade ≥ 2 or Grade ≥ 3 Genitourinary Toxicity Fo...

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.

Introduction

In 2016, the estimated number of new cancer cases was projected to be 1.68 million, of which pelvic malignancies were expected to account for approximately 19%.[1] Based on current trends, the projected prevalence of cancer survivors in 2024 is predicted to exceed 18 million people; survivors of pelvic malignancies are expected to account for 31% to 40% of that number.[2] Over the last several decades, a tremendous focus on improving cancer therapies has led to improved cancer survival.

Genitourinary and sexual morbidity may result from these improved cancer treatments, especially in patients treated for pelvic malignancies. During treatment, focusing on cancer care is paramount; however, after treatment, many patients report difficulty with adjusting to the changes in their physical appearance, functioning, and social roles that often result from aggressive therapies. These issues have resonated in our society, leading to a growing interest in enhancing healthcare system support and programs for cancer survivors. In 2004, the President’s Cancer Panel published a report highlighting the need for improvement in education on and awareness of late side effects, establishment of follow-up care plans, and optimization of regulations to facilitate cancer survivorship support.[3] Foundational to all such efforts is that practitioners have a clear understanding of the urinary and sexual sequelae of treatments used for pelvic malignancies, which will enable them to help these patients manage the factors that affect their quality of life (QOL) in survival.

Herein we describe some of the most common sexual and genitourinary side effects encountered following treatment of pelvic malignancies.

Urinary and Sexual Effects of Surgical Treatment of Colorectal Malignancies

Urinary and sexual dysfunction are common sequelae of treatment for colon and rectal malignancies. The incidence of these in the existing literature is highly variable due to the difficulty in capturing functional outcomes. However, it is estimated that between 12% and 70% of patients have some degree of urinary dysfunction, with sexual dysfunction an even more common problem.[4-7]

REPRESENTATIVE CASE 1

A 66-year-old man with a history of Gleason 4+3=7 prostate cancer treated 2 years earlier with external beam radiation therapy and hormonal ablation presents with worsening erectile function and urinary incontinence. He has no evidence of disease recurrence. He reports that his urinary incontinence is affecting his social interactions and that his erectile dysfunction is causing relational stress. Physical examination reveals incontinence induced by stress maneuvers. The patient is in diapers and his pad weight demonstrates 550 gm of urine leakage in a 24-hour period. His blood work shows recovery of his testosterone level. Given the degree of leakage and history of radiation, an artificial urinary sphincter is placed. On follow-up, he uses only one mini pad for protection during strenuous activity. He is able to socialize without concern regarding a bothersome urine odor. For his erectile dysfunction, he was started on a phosphodiesterase type 5 inhibitor, which has allowed him to obtain an erection firm enough for intercourse. These treatments have increased his quality of life, as demonstrated by patient-reported outcomes surveys.

Depending upon the size and location of a tumor, several operative approaches can be utilized for curative resection. Although an abdominoperineal resection carries a greater risk of sexual or urinary dysfunction than a low anterior resection, the autonomic nerves responsible for normal urinary and sexual function are at risk with both surgical approaches.[8]

High ligation of the inferior mesenteric artery requires dissection around the superior hypogastric plexus. Dissection along the lateral pelvic sidewall requires identification of pelvic autonomic nerves. Total mesorectal excision, a technique developed in the 1970s to improve oncologic outcomes, has had the added benefit of facilitating identification and preservation of these structures, which can result in preservation of urinary function.[9,10]

The use of minimally invasive surgical approaches has become increasingly widespread because of their association with improved perioperative outcomes and oncologic equivalence. However, despite anticipated benefits, including improved visualization of key structures during pelvic dissection, neither laparoscopic nor robotic approaches have been shown to reduce the incidence of genitourinary side effects.[5,11]

Neoadjuvant radiation therapy (RT) is a key component of the multimodal approach to rectal cancer because of its ability to downstage disease, turning unresectable tumors into resectable surgical targets. The use of pelvic RT for colorectal cancer does not appear to have any impact on the postoperative incidence of urinary dysfunction; however, it has been associated with significantly worsened sexual function in both men and women.[6,12-14]

Urinary and Sexual Effects of Surgical Treatment of Prostate Cancer

A well-recognized concern associated with surgical management of prostatic malignancy is the subsequent risk of urinary incontinence and erectile dysfunction. Urinary continence may depend on a combination of function of the external urinary sphincter, the patient’s age and body mass index, urethral length, whether a nerve-sparing technique was used, and the surgeon’s experience.[15-17] The spectrum of outcomes is wide and may range from complete urinary control to total incontinence.

Immediately after prostatectomy, the majority of patients experience urinary leakage that improves over the course of 3 to 12 months. A recent study evaluating health-related QOL outcomes in 708 men following prostatectomy demonstrated that at 3 months after surgery, the rate of continence was 39%. These rates improved over time.[18] Continence rates at 12 months after open or robotic prostatectomy performed by an experienced surgeon can be expected to be between 74% and 96% (Table 1).[18-30] The most common type of incontinence in the postprostatectomy setting is stress incontinence. However, a subset of men may also experience urge or mixed urinary incontinence. Men bothered by the degree of their incontinence should be considered for anti-incontinence procedures following a thorough urologic evaluation, although many practitioners will wait 6 to 12 months after the prostatectomy before considering an anti-incontinence procedure. We feel strongly that significant incontinence that has stopped improving early in the post-recovery period should be addressed with the patient at this time.

Erectile dysfunction is an even more common side effect of surgical management of prostate cancer. Walsh et al revolutionized the way prostatectomies are performed by describing the technique of a nerve-sparing prostatectomy, which allows erectile function to be preserved in a number of men.[31] Despite this advance, preserved erectile function rates still range between 50% and 80% in most studies. However, there is some discrepancy between provider-reported outcomes and patient-reported outcomes. The rate of adequate erectile function in this patient cohort may be lower than the rates reported in studies.[18] A recent prospective analysis of patient-reported outcomes in 1,643 men demonstrated that at 24 months, 81% of patients treated with prostatectomy had erections that were not firm enough for intercourse. This is compared with 53% of men on active surveillance and 66% of men who had undergone RT. Sexual dysfunction was reported as a moderate or severe problem in 57.5% of patients who had undergone prostatectomy, compared with 34.4% of patients on active surveillance, and 36.6% of patients treated with RT.[26]

A growing body of literature now recognizes additional sexual function effects, including climacturia (urinary leakage during orgasm) in 22% to 29% and orgasmic pain in 7% to 14%.[32-35] Few data exist regarding management of climacturia; however, one randomized controlled trial demonstrated improvement with implementation of pelvic floor muscle training (PFMT).[36] Rates of climacturia were similar between patients treated with open prostatectomy and those treated with robotic prostatectomy. However, orgasmic pain occurred with more frequency in the open prostatectomy patients.[33]

Urinary and Sexual Side Effects of RT for Prostate Cancer

Radiation toxicity has two components: the acute toxicity experienced during treatment, which typically resolves within 4 to 6 weeks of treatment ending, and late or chronic toxicity, which is less common but more persistent when it does occur.

A prospective longitudinal study of patient-reported QOL outcomes after prostatectomy, brachytherapy, or intensity-modulated radiation therapy (IMRT) reported that overall, RT modalities resulted in less urinary incontinence but more irritative symptoms compared with surgery.[37] This finding mirrors earlier data comparing the three modalities just mentioned, although the later study showed a decrease in acute urinary toxicity across all treatment types.[38,39]

REPRESENTATIVE CASE 2

A 48-year-old woman with a history of cervical cancer who was treated 8 years earlier with brachytherapy and external beam radiation therapy presents with long-standing urinary frequency and urgency, incontinence, and mild hematuria. She has been treated on multiple occasions for urinary tract infections resulting from her symptoms, but these have persisted. She voids every 30 minutes and occasionally experiences leakage between voids despite antimuscarinic therapy. Bladder evaluation with videourodynamics and cystoscopy reveals a low-compliance bladder, significantly reduced capacity (80 mL), uninhibited contractions, high storage pressures, left-sided vesicoureteral reflux, and mucosal friability. Imaging of the upper urinary tract shows contralateral distal ureteral stricture with hydronephrosis secondary to radiation damage. Bladder and ureteral biopsy demonstrate histologic changes consistent with radiation effect. Because of her contracted and hostile bladder parameters, she chose to undergo a cystectomy with a continent urinary diversion. Following her recovery, she has been catheterizing her urine reservoir 4 to 6 times per day, without leakage concerns or pelvic discomfort.

Factors associated with late genitourinary toxicity include the presence of acute genitourinary toxicity during treatment, advanced patient age, previous transurethral resection of the prostate, large prostate volume, diabetes, pretreatment use of α-blockers, and certain bladder dose parameters (Table 2).[40-43] In a study using the Expanded Prostate Cancer Index Composite (EPIC)-26 health-related QOL questionnaire to compare IMRT, brachytherapy, and stereotactic body radiotherapy (SBRT), brachytherapy was associated with greater change in urinary symptoms than IMRT or SBRT.[44] A subanalysis of one arm of a randomized trial compared patient-reported QOL outcomes associated with three-dimensional conformal RT vs outcomes associated with IMRT and found no differences between these modalities.[45]

In some men, postprostatectomy radiotherapy (PORT) may be needed, with clinical indications including positive surgical margins. When this occurs, the toxicity of surgery and RT overlap, and some distinct trends can be noted. First, prospective data comparing patients who underwent PORT following prostatectomy vs prostatectomy patients who did not undergo PORT have shown that urinary incontinence continues to improve after PORT.[46] However, the degree of continence reached in this study was diminished in the nonrandomized PORT arm compared with the men who never required salvage RT. In a secondary analysis of randomized trial data by Mark et al, less acute urinary toxicity is associated with PORT compared with primary RT to an intact prostate.[47] No difference in late urinary toxicity was noted between men who received RT to intact prostates and men who received postoperative bed irradiation.

Sexual dysfunction presents quite differently in RT patients compared with those who are treated with surgery alone. While the exact mechanism is unclear, it is hypothesized that radiation injury to the neurovascular bundles and the penile bulb ultimately results in erectile dysfunction over time, with the mechanism possibly involving apoptosis of the periprostatic cavernous nerve cells.[48,49] Clinically, this damage may present as slowly progressive erectile dysfunction.

Prospective patient-reported QOL studies show that the change from baseline function varies between modalities, with sexual function less affected by RT than by surgery.[37] Older studies demonstrate an initial dip in patient-reported sexual function at the time of treatment with either RT or surgery, then recovery, and then slow decline. However, the initial decline in sexual function in these studies is greater for surgery than for RT.[38,39]

Anejaculation is a near-universal but under-addressed side effect of prostate RT. A prospective study of men undergoing external RT or brachytherapy found that 89% of men reported anejaculation 5 years after treatment.[50] This side effect was more common in older men treated with brachytherapy or androgen deprivation therapy (ADT) or those whose pretreatment prostate size was small.

Urinary and Sexual Side Effects of RT and Surgical Treatment for Gynecologic Malignancies

Treatment of gynecologic malignancies may adversely affect both sexual and urinary function. In a survey of more than 1,200 survivors of gynecologic malignancies, one-third of the women experienced sexual or urinary dysfunction during or after cancer treatment.[50] Among women with cervical cancer, over 40% reported difficulty in one or both of these areas.[51]

The mechanisms underlying patient-reported outcomes may differ based on treatment modality. The performance of a radical hysterectomy for early-stage cervical cancer results in vaginal shortening, with the possibility of decreased lubrication and/or fibrosis, which can result in dyspareunia.[52] Sexual arousal or orgasm may be affected by autonomic nerve damage.[53] RT for advanced or recurrent cervical cancer in premenopausal patients leads to premature ovarian failure if the ovaries have not been moved out of the radiation field, with resultant vasomotor symptoms and vaginal dryness.[52] Survey data suggest that women who receive RT for management of cervical cancer are more likely to experience sexual dysfunction compared with women who undergo other treatment modalities.[51]

Urinary dysfunction may worsen or persist for many years after cervical cancer treatment, as in the patient in Case 2.[51] The mechanism differs depending on treatment modality; for those treated with initial surgical management, urinary symptoms may be due to changes in nerve supply and pelvic floor anatomical relations. Irritative and obstructive symptoms have been reported as more frequent than stress-related symptoms in patients who undergo radical hysterectomy. Long-term urinary problems may occur in 30% of patients who undergo radical hysterectomy and debilitating problems may occur in up to 16%.[54] Outcomes of RT for cervical cancer have been urodynamically compared with those achieved with radical hysterectomy. Patients who underwent RT had decreased bladder compliance and increased bladder sensation.[55] Urinary dysfunction in patients treated with RT, specifically incontinence, may be secondary to fistula formation. In this setting, the possibility of recurrent disease should be assessed first.

Although they are in the minority, premenopausal women with endometrial cancer may enter surgical menopause as a result of a bilateral salpingo-oophorectomy performed as part of the staging procedure. Not surprisingly, survey data demonstrate that women under the age of 40 at diagnosis may be most at risk for sexual side effects of endometrial cancer treatment.[51] The use of RT in the management of endometrial cancer increases the likelihood of urinary complaints. Women undergoing multimodality treatment with surgery, chemotherapy, and RT are at highest risk.[51] Sexual dysfunction, rather than urinary tract complaints, is more common in women who are treated for ovarian cancer, perhaps because RT is seldom used in the management of this malignancy.[51]

Despite the prevalence of sexual dysfunction in survivors of gynecologic malignancies, only a small fraction of women seek care for these issues, suggesting a need for members of the healthcare team to actively inquire about these symptoms.[56]

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