© Springer International Publishing Switzerland 2016Jaspreet S. Sandhu (ed.)Urinary Dysfunction in Prostate Cancer10.1007/978-3-319-23817-3_1
1. Introduction: Urinary Function Alterations in Men with Prostate Cancer
Department of Urology, University of Vermont, Burlington, VT, USA
Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, 353 E 68St., New York, NY 10065, USA
Jaspreet S. Sandhu
The prostate gland plays an integral role in male reproduction during young adulthood. Its anatomic location, between the bladder and the membranous urethra, means that it is also an important part of the urinary voiding pathway and has a significant bystander effects on urinary function. The prevalence of urinary dysfunction, specifically lower urinary tract symptoms (LUTS) and urinary incontinence, increases as men age. LUTS in men is thought to be primarily a sequelae of benign prostatic hypertrophy (BPH), increases as men age as shown in multiple large longitudinal studies [1, 2]. As a rule of thumb, roughly half of men over the age of 50 suffer from some degree of LUTS. Urinary incontinence in community dwelling men, similarly, increases as men age. 11 % of men over the age of 65 without a history of prostate cancer or prostate surgery admit to suffering some degree of incontinence, increasing to 35 % in men over the age of 85 . Prostate cancer afflicts elderly men and it is in this background that urinary function alterations after prostate cancer should be measured.
The control arm in one of the largest randomized trial performed to comparing radical prostatectomy as treatment for prostate cancer to an untreated “watchful waiting” cohort showed that untreated localized prostate cancer leads to slight worsening ofurinary obstructive and irritative symptoms but not urinary incontinence .
It appears that LUTS due to prostate cancer in-situ behaves very much like LUTS due to BPH with the possibility of much faster progression. It is because of this reason that in men who have not had local treatment for prostate cancer, surgical modalities such as transurethral resection of the prostate (TURP) appear to be effective in relieving LUTS. Unfortunately, unlike TURP in the setting of BPH, TURP in the setting of locally advanced prostate cancer appears to be less durable likely due to continued tumor growth .
Urinary function alteration after local treatment for prostate cancer has been studied extensively, particularly in patients treated with radical prostatectomy or radiotherapy. Most studies show very similar results leading to an excellent understanding of the natural history of urinary function alterations after these treatments. Unfortunately, modalities such as cryotherapy, high-intensity focused ultrasound, focal therapy, and others do not have robust clinical data with respect to urinary adverse events.
Urinary Function After Radical Prostatectomy
Urinary function after radical prostatectomy changes dramatically in the short-term after radical prostatectomy . Urinary incontinence, in particular, causes significant distress in men who have undergone radical prostatectomy .
Longitudinal studies show worsening urinary incontinence immediately after radical prostatectomy with subsequent improvement over the course of the next few months. Sanda et al. sought to qualify predictors of quality of life following patients who underwent treatment for prostate cancer and determine their effect on both the patient and partner. A total of 1201 patients were evaluated both pre- and post-treatment up to 24 months post treatment. Men who underwent prostatectomy reached a nadir in Quality of Life scores at 2 months post operatively which then improved over the following 24 months . Irritative and obstructive scores improved to better than baseline over the study period. This finding was confirmed in another study by Pardo et al. A total of 435 patients were prospectively evaluated prior to treatment with prostatectomy, external beam radiotherapy or brachytherapy. Immediately post treatment, the prostatectomy cohort had worse incontinence quality of life scores at 36 months, but improved obstructive and irritative voiding symptoms. In patients with obstructive symptoms at baseline, 64 % of patients noted improvement above pretreatment . Saranchuk et al. prospectively evaluated urinary function in 647 consecutive men undergoing radical prostatectomy and noted that full continence, defined as no pad use per day, was achieved in 87 % of men at 12 months which increased to 93 % at 2 years .
Multiple factors have been implicated in helping to achieve an earlier and more complete return to continence post-prostatectomy. Younger age has been shown to promote an earlier return to continence, as has preservation of the neurovascular bundles, lower body mass index (BMI), absence of anastomotic stricture, lower number of comorbidities, no prior radiotherapy for prostate cancer, and increasing membranous urethral length [9–11]. Grade, stage, and PSA were once thought to be associated with postoperative continence, but this may be attributed to nerve-sparing status instead . Nerve-sparing status was found to decrease the median time to continence from 5.6 to 1.5 months in a study by Eastham et al. .
Multiple intraoperative maneuvers have also been described as well to help with postoperative continence. The role minimally invasive prostatectomy on subsequent incontinence remains unresolved.
Increasing age is an independent preoperative predictive factor for postoperative incontinence. Matsushita et al. evaluated 2849 patients and noted increasing age, higher ASA score, increasing BMI, and lower membranous urethral length were adverse independent predictors of subsequent continence recovery . Age greater than 65 years of age has been associated with increased rates of incontinence and incomplete recovery of continence . In a review of 581 consecutive patients, 91 % of patients were continent at 24 months and age less than 65 was the strongest correlate with recovery of continence . In a prospective analysis by Licht et al., age greater than 65 years was an independent predictor of incontinence . This reflects rates of continence in the aging male population as a whole. Anger et al. in a review of National Health and Nutrition Examination Survey have found that incontinence rates rose from an overall prevalence of 17 % in men younger than 60–31 % in men older than 85 .
Matsushita et al. showed an independent relationship between increasing BMI and subsequent incontinence, though there are some conflicting results . Mulholland et al. demonstrated no association in body mass index and continence based on questionnaires related to voiding dysfunction over a 2 year period . Conversely, Anast et al. showed that higher BMI was associated with worse urinary function, but not necessarily worsened quality of life after a review of the CaPSURE database . This may have been associated with increased BMI leading to a higher rate of anastomotic stricture seen in a separate review of the CaPSURE data .
Smaller prostate volume has been suggested to result in improved continence rates; however, Eastham et al. found no association between prostate size and recovery of continence on multivariate analysis [10, 17]. Konety et al. reviewed the CaPSURE database for those patients with prostate volumes recorded and noted that prostate volumes less than 50 g were associated with improved continence rates; however, this difference normalized at 24 months postoperatively .
Newer modalities, such as laparoscopic or robotic prostatectomy, show similar results. Unfortunately, the difference in incontinence between open and MIS surgery has proven difficult to quantify because of the fact that very few surgeons offer both techniques contemporaneously. Furthermore, most comparisons have been between surgeons experienced in performing open surgery and those that have recently adopted MIS surgery, making conclusion problematic given effect of new technology and surgical learning curve.
Anastomotic Stricture After Radical Prostatectomy
Anastomotic stricture , or bladder neck contracture is a relatively uncommon, but well-known complication following radical prostatectomy. These patients tend to present in the first 6 months postoperatively [18, 19]. The economic impact of symptomatic urethral and anastomotic strictures is not insignificant, with one study documenting the cost at approximately $6000 per affected individual .
The rate of anastomotic stricture has been reported between 2.5 and 25.7 % in up to 62 % of patients who undergo radiotherapy [16, 18]. The wide range may be due in part to differences in data collection, patient population, surgeon practice patterns, and postoperative follow-up. These strictures are troublesome to manage, as they often require multiple procedures and intervention may lead to worsening of incontinence.
Risk factors for development of anastomotic stricture are similar to those seen for continued incontinence post prostatectomy and included age, increased BMI, renal insufficiency, presence of postoperative leak or hematoma . Individual surgeon technique and experience appear to greatly influence the development of strictures.
In a review of the SEER-Medicare linked database, Begg et al. noted a decreased rate of urinary complications, primarily anastomotic strictures, with higher volume surgeons . Higher BMI and lower risk cancer were found to be associated with stricture formation upon review of the CaPSURE database .
With the rise in minimally invasive prostatectomy, a decrease in anastomotic strictures has been noted. Sandhu et al. found a roughly tenfold lower rate of anastomotic stricture in those patients undergoing MIS prostatectomy . This was also noted in a SEER-Medicare linked database review by Hu et al. which showed that MIS prostatectomy was associated with 5.8 % rate of claims for bladder neck contracture versus 14 % for open . In a retrospective review of 52 patients, Boroboroglu noted mucosal eversion during the vesicourethral anastomosis has been linked to decreased stricture formation and may present a possible explanation for the decreased stricture rate in minimally invasive prostatectomy. Other factors they noted on multivariate analysis included intraoperative blood loss, increased operative time, smoking, and coronary artery disease were also linked with development of bladder neck contracture .
The majority of these interventions are successful early; however, there is a subset of patients that require multiple interventions or further reconstruction. Most contractures are managed conservatively with dilation or transurethral incision, with success rates ranging between 50 and 87 % [ 19].
Urinary Function After Prostate Radiotherapy
Prostate radiotherapy is another option frequently used either alone or combined with androgen deprivation therapy (ADT) in patients with localized prostate cancer. Quality of life is often a factor in patient’s decision making regarding which modality of treatment to undergo. A baseline voiding history should be undertaken as those patients with preexisting voiding dysfunction may experience worsening of their symptoms and should be counseled accordingly.
The Prostate Cancer Outcomes Study evaluated 3533 men and followed them for over 15 years to look at long-term functional outcomes of those patients undergoing treatment for localized prostate cancer. After 15 years, no difference was noted in the rates of urinary incontinence between those who underwent prostatectomy and those undergoing radiotherapy. Other voiding dysfunction was not assessed however . Sanda noted an initial worsening of symptoms after external beam radiotherapy, albeit not as severe as seen post-surgery with an eventual return to baseline over 24 months. In those patients undergoing brachytherapy, symptoms did not return to baseline following treatment and patients were more likely to note persistent distress after 2 years. Eighteen percent of those patients undergoing brachytherapy reported moderate to severe distress at 12 months following initiation of treatment, compared to 11 % post radiotherapy and 7 % post prostatectomy . A study by Ghadjar et al. also performed a prospective analysis of urinary toxicity following both external beam and brachytherapy . Most patients had a QoL score on the AUA Symptom Index of 2. This did not change throughout treatment as a whole. Twenty-eight percent of patients experienced acute Grade 2 toxicity, with 20 % continuing to have Grade 2–3 symptoms at more than 3 months beyond treatment. Grade 2 toxicity was described as urinary dysfunction requiring alpha blocker therapy. Grade 3 required catheterization or post-procedural transurethral resection of the prostate. Late Grade 3 toxicities were due primarily to urinary retention and were not associated in conjunction with Grade 2 toxicity . At 3 years, the rate of urethral stenosis, incontinence, and hematuria were 6.6 %, 4.8 %, and 3.3 %, respectively, in a study by Fiorino .
Preoperative predictive factors include a PVR of greater than 100 cc, pre-procedural AUA symptom score of greater than 8, bladder outlet obstruction seen on urodynamics, prostate volume greater than 40 cc, and peak flow of less than 10 cc/s [27–29].
Large prostates were associated with persistent urinary toxicity in those patients undergoing both external beam and brachytherapy. In the study by Sanda et al., large prostate was defined as greater than 50 g .
At 1 year, 5 % of partners reported being bothered by the patient’s incontinence. In the same cohort 7 % of partners were bothered by the patient’s obstructive symptoms in those undergoing brachytherapy, compared to 3 % undergoing external beam radiotherapy .
Patients who present with urinary toxicity are managed medically initially, usually with alpha blocker therapy . Anticholinergics have been used with some success for patients with persistent irritative voiding symptoms refractory to alpha blocker therapy alone . Surgery may ultimately be indicated, but this may render the patient incontinent, necessitating careful and thorough counseling of the patient. Patient selection is also key in this situation. A history of a patient with new onset obstruction without prior voiding symptoms who is obstructed on urodynamic testing may benefit from resection. In a retrospective review of 38 patients who underwent TURP following brachytherapy, 18 % were incontinent post procedure. Median time to TURP was 11 months . Incidence of rectourethral fistula is also higher and should be explained to patients as well. Aggressive anterior resection should be avoided to prevent development of pubovesical fistula .
Fistulae are late complications that result from instrumentation such as cystoscopy or colonoscopy in patients who have had prior radiation. Repair of rectourethral fistula is rendered more complicated secondary to the decreased vascularity of tissue surrounding the fistula and usually requires permanent diversion . This is similar to data seen for pubovesical fistulae. Patients typically presented with urethral stricture and underwent endoscopic treatment. Conservative management was typically unsuccessful with most patients undergoing eventual cystectomy .
Radiation may also be used as a salvage therapy in patients who have undergone first line treatments for their prostate cancer. In a recent meta-analysis grade 3–4 toxicity was found to be significantly higher in the salvage brachytherapy group, occurring in 12.9 % of patients. Incontinence was reported in 6.2 and 3.1 % developed recto-urinary fistula . Tharp et al. however reported toxicity of urethral necrosis and incontinence in 29 % of their cohort with a median of 58 month follow-up .
Emerging Topics in Urinary Dysfunction After Prostate Cancer
Urinary Function Recovery After Prostate Cancer Ablation
New data is emerging as short term studies arise regarding voiding dysfunction following whole gland ablation. TheCOLD database is a database of all men undergoing cryotherapy , both focal and whole gland, in both primary and salvage settings. 4099 patients underwent whole gland cryoablation between 1999 and 2007. In the report of complications 65/2099 (3.1 %) reported de novo incontinence. 18/2099 (0.4 %) developed rectourethral fistula, and 34/2177 (1.6 %) had urinary retention persisting more than 30 days post procedure . A recent study evaluating urodynamic outcomes saw decreased bladder compliance and de novo overactive bladder in 10 % of patients at 3 months post-procedure, improving by 6 months follow-up. At 6 months, the cohort showed decreased Pdet, and Qmax on uroflowmetry. Those patients with large prostates continued to have voiding dysfunction at the 6 month procedure period . Another study with a median of 27 months follow-up showed urethral stricture formation requiring dilation in 13.8 % of patients. Bladder neck incision was required in 9.2 %. Before treatment 73.3 % of patients did not leak, post treatment 55 % of patients did not leak. 2.7 % of patients did not require pads pretreatment, increasing to 9 % following treatment .