CLIMACTURIA AFTER RADICAL PROSTATECTOMY: MRI-BASED PREDICTORS

INTRODUCTION

Individuals with clinically localized prostate cancer (PCa) have favourable long-term overall and cancer-specific survival regardless of whether they decide upon surgery or radiation therapy with curative intent [1]. As such, the morbidity and specific side effect profiles related to these treatment modalities has been central to patient counselling and treatment decision making.

The two most common complications associated with radical prostatectomy (RP) reported in the literature are sexual dysfunction and urinary incontinence [2]. Sexual dysfunctions include erectile dysfunction, penile deformities, low sexual desire, couple’s relationship distress, and ejaculatory and orgasmic dysfunctions (decreased ejaculation, sexual incontinence, decreased orgasm and dysorgasmia) [3, 4]. Sexual incontinence is one of the least considered complications of RP, although it appears in many men after surgery [5, 6]. Sexual incontinence includes climacturia (orgasm associated incontinence), which consists of the leakage of urine around the time of orgasm and arousal incontinence, which consists of urine loss during foreplay [6]. Initially described by Koeman et al in 1996[7], climacturia occurs commonly post RP, with more contemporary studies suggesting approximately 30% of men will experience it on at least one occasion [6, 8]. Some studies have tried to find predictive factors for climacturia [6, 9–11], with Choi et al identifying shorter time since surgery as being an independant predictive factor [6].

As yet the mechanism of climacturia after RP remains unknown with differing views on the predominant roles of both the internal [7] and external sphincter [12] respectively. There is however increasing evidence that preoperative pelvic anatomy can play a role in postoperative urinary continence [13–17]. This analysis was performed to attempt to find preoperative pelvic MRI parameters which might be predictive of post-RP climacturia.

MATERIALS AND METHODS

A retrospective analysis of a prospectively constructed database of patients attending the sexual medicine service at our institution was performed. Patients attended for the evaluation of post-RP sexual dysfunction. This database was elaborated under the institutional ethics committee approval.

Study Population:

We retrospectively reviewed this existing sexual medicine database and cross referenced it with a second institutional database of all men (n=4,053) who underwent pelvic staging MRI prior to RP performed by 1 of 7 dedicated prostate surgeons at our institution. One hundred and ninety four patients met the primary inclusion criteria of (i) having undergone a pre-RP pelvic MRI, (ii) received no adjuvant therapy for their prostate cancer, (iii) were sexually active (self or partner) and (iv) had full pre and postoperative data available.

Climacturia Assessment:

As a routine part of a patient’s sexual health evaluation after RP, at the initial visit they were asked to fill in a questionnaire about their demographic data, past medical and surgical history, and baseline and post operative sexual function parameters including erection, desire and orgasm (presence/absence, presence of pain, intensity, ease of achievement and sexual incontinence, including climacturia). Since many men report climacturia on at least one occasion after RP, we selected the threshold of >3 climacturia events as an inclusion criterion.

Daytime continence was assessed based on patient self-report and defined as the use of no pad or a safety one (removed dry). BMI was calculated with reported weight and height, Hospital medical records further supplemented patient information about prostate cancer characteristics, and nerve sparing status. For each neurovascular bundle (one on each side of the prostate), the surgeon was asked to assign a number from 1 (complete preservation of the nerves) to 4 (complete resection of the nerves), with each patient having a post-surgical nerve sparing score of anything from 2 (complete preservation of both nerves) to 8 (complete resection of both nerves)[18, 19].

MRI Imaging and Measurements:

MRI measurements were performed on axial, sagittal and coronal planes by 2 independant raters on preoperative endorectal MRI scans. Both raters were blinded to all clinical and pathological data. All measurements were defined by a dedicated MRI body radiologist. Training was performed under supervision and the accuracy of the measurements was confirmed by the radiologist.

Figure 1 demonstrates each defined measurement performed. The mid pelvic area (MPA), levator thickness at the height of apical dissection, outer levator distance (OLD), inner levator distance (ILD), urethral volume and prostate volume were calculated. MRI was performed on a 1.5 Tesla system (Signa™). A body coil for excitation and a pelvic phased array coil were used in combination with an endorectal coil (Medrad, Pittsburgh, Pennsylvania) for signal reception. Transverse spinecho T1-weighted images were obtained through the pelvis with specific parameters including repetition time/echo time 400–600 msec/8–10 msec, section thickness 5 mm, intersection gap 1 mm, field of view 24 cm, matrix 256 × 192 and 2 signals acquired. Thin section, high spatial resolution transverse, coronal and sagittal T2-weighted fast spin-echo images were obtained through the prostate and the seminal vesicles with the specific parameters of repetition time/echo time 4,000–6,000 msec/96–120 msec, echo train length 12–16, section thickness 3 mm, intersection gap 0 mm, field of view 12–14 cm, matrix 256 × 192 and 4 signals acquired. Automated correction was applied to the T1-weighted and T2-weighted images for the reception profile of the endorectal and pelvic phased array coils.

Figure 1:

1, symphysis angle, defined as angle between long axis of symphysis pubis and horizontal (midsagittal T2-weighted image). 2, apical depth of prostate. Vertical measurement from most proximal margin of symphysis pubis to level of distal margin of prostatic apex (midsagittal T2-weighted image). 3, maximum height of prostate measured from prostate base to apex at any level (midsagittal T2-weighted image). 4, lower conjugate of pelvic midplane, defined as distance from lower inner symphysis pubis to sacrococcygeal junction (midsagittal T2-weighted image). 5, bony femoral width, defined as bony width of pelvis at mid femoral head level (axial T1-weighted image). 6, urethral width, defined as maximal diameter of urethra (axial T2-weighted image). 7, OLD, defined as distance from outer border of levator muscles measured at same level as ILD (axial T2-weighted image). 8, ILD, defined as narrowest distance from inner border of levator muscle to urethra below caudal margin of prostatic apex (axial T2-weighted image). 9, urethral length, measured from apex of prostate to base of urethral bulbus (coronal T2-weighted image). 10, maximal prostate width (axial T2-weighted image). 11, maximal prostate length measured at same level as maximal width (axial T2-weighted image).

Statistical Methods:

Independent samples t-test and Chi-square test were used to test univariate associations with climacturia. Patient age, BMI, comorbidity presence, RP nerve sparing score and all MRI parameters were analyzed as potential predictors. Parameters that produced a p value < 0.20 on univariate analysis were included in the multivariable analysis logistic regression model. Inter-rater agreement of the various MRI measurements was evaluated according to a procedure described in a previous study [13]. All analyses were performed using Stata® 10.1.

RESULTS

Patient Population:

A total of 194 patients were included in the analysis, 138 patients without and 56 with climacturia with mean ages in both groups being comparable: 60±8 and 59±7 years old respectively. Table 1 illustrates pertinent variables in the patient population. The average time between surgery and the first post-operative assessment was 7 ± 7 months. The rate of nerve sparing was equivalent in both groups (with mean nerve sparing score 3.5 ±1.6 among patients without climacturia and 3.2 ±1.3 among those with climacturia, p=0.2. Daytime continence was also comparable between both groups. We found, however, a clear tendency for men with higher body mass index (BMI) to develop climacturia (28 4 vs 27±3, p=0.02).

Table 1:

Patient Demographics and Operative Details

	Without Climacturia	With Climacturia	p
Patient number (194)	138	56
Mean age (years)	60 ± 8	59 ± 7	0.4
Mean nerve sparing score (2–8)	3.5 ± 1.6	3.2 ± 1.3	0.2
Bilateral nerve sparing	71%	69%	0.8
Continent	86%	79%	0.2
Mean BMI	27 ± 3	28 ± 4	0.02

Inter-rater agreement MRI measurements:

Two separate readers, blinded to clinical and pathological data, evaluated MRI measurements in a subgroup of patients (n=100). Overall, readers showed moderate or better agreement for all MRI variables (weighted kappa ≥0.48 for all MRI measurements).

Predictors of Climacturia:

On univariate analysis (Table 2), only BMI, urethral width and lower urethral conjugate, prostate depth, levator thickness and outer levator distance met the criterion for multivariable analysis. In the multivariable model (Table 3), only urethral width was associated with climacturia (OR 1.34, 95% CI 1.05–1.71, p = 0.02), the wider the urethra, greater the chance of climacturia.

Table 2:

Univariate Associations

	Without Climacturia	With Climacturia	p
Urethral width (mm)	11.6	12.2	0.02
Lower conjugate (mm)	103.6	106.5	0.04
Depth of prostate (mm)	25.9	28.0	0.10
Outer levator distance (mm)	38.5	40.1	0.01
Urethral length (mm)	13.6	12.6	0.16
Levator thickness (mm)	11.2	11.7	0.04

Table 3:

Multivariate Associations

Variable	OR	95% CI	P
Urethral width (mm)	1.34	1.05–1.71	0.02
Lower conjugate (mm)	1.03	0.99–1.08	0.2
Depth of prostate (mm)	1.03	0.97–1.08	0.3
Outer levator distance (mm)	1.05	0.92–1.21	0.4
Urethral length (mm)	0.95	0.86–1.04	0.2
Levator thickness (mm)	1.04	0.75–1.44	0.8
BMI (5 point increase)	1.81	0.93–3.50	0.08

DISCUSSION

Sexual dysfunctions after PCa treatment are common and are associated with a significant impact on QoL for patients [20, 21]. Although erectile dysfunction is the most studied condition, little is known about other sexual disorders [3]. Sexual incontinence was first described by Koeman et al in 1996, who found it in 7/14 of the patients who undertook an interview and a questionnaire after having undergone RP [7]. The term climacturia was first employed by Koeman et al in 2006 [7].

Reported rates of climacturia vary from 16–93% [5–7, 9–11, 22]depending on the time after RP when assessed, definition of the condition, patient characteristics, type of symptom assessment (which questionnaire was used or which question was asked by investigators).

There is conflicting data regarding the impact of this condition on couples’ sexual life. Some authors report none or very little bother [11, 23], while others have described over 50% of men being psychologically affected [7, 9, 10, 24]. Nilsson et al found that patients suffering from climacturia after RP have significantly more sex avoidance because of fear of failing along with, low self-esteem, and higher rates of depressed mood and anxiety.

The cause of climacturia in post-RP men is not clear. It is well known that during normal orgasm both external and internal urethral sphincters close to generate a high pressure chamber within the prostatic urethra, and immediately after, the external sphincter opens (while the internal remains closed, to avoid retrograde ejaculation). Helped by the rhythmic peri-urethral muscular contractions, semen is propelled in an antegrade direction. There is also an increase in bladder tonicity (28). One hypothesis for the mechanism underlying climacturia is the ineffective bladder neck coaptation allowing urine to be expelled during orgasm, while external sphincter is relaxed [7, 25]. This may also explain why climacturia has been seen after transurethral resection of the prostate [9]. Furthermore, the fact that climacturia ameliorates over time [6, 9], is consistent with bladder neck healing and functional restoration of the internal sphincter after RP.

Manassero et al studied patients suffering from climacturia after RP. They performed video-urodynamics in 7 climacturic patients and 5 controls (all of them day-time continent). They reported the climacturia group had a statistically significant reduced functional urethral length compared with controls, as well as a longer time to continence recovery. They found also a trend (without achieving significance) to lesser maximum urethral closure pressure at the external sphincter in climacturia sufferers [26]. These data support our findings, in that, we observed a statistical significant relationship between wider urethral widths and presence of climacturia (OR 1.34).

Another study analyzing urethral pressure before and after RP in 34 patients, observed a decrease in maximal urethral closure pressure after surgery, both in continent and incontinent men, but this parameter was significantly lower in incontinent patients [27]. Lee et al. also suggested this theory in 2006 (the wider the bladder neck or the urethra, the higher the probability of developing climacturia), but they could not prove it at that time [24].

In contrast to Manassero’s results, we did not find an association between climacturia and urethral length (p=0.2). However this is likely explained by the fact that they performed imaging after surgery. Preoperative urethral length has also been found to be a predictive factor for urinary continence recovery in other studies [13, 14].

Our analysis did not demonstrate any association of the existence of climacturia with degree of nerve sparing status at time of RP (mean nerve sparing score 3.5 ±1.6 among patients without climacturia and 3.2 ±1.3 among those with climacturia, p=0.2). Although these scores are subjective assessments at the time of surgery, they have been validated in other studies to predict post operative erectile function recovery and return to baseline sexual function [28–30]. The lack of association may suggest that a more substantial component of the etiology of climacturia may be related to iatrogenic sphincter damage at time of surgery then the degree of cavernous nerve preservation proximally when removing the prostate gland. The limitations of this analysis are firstly that the endorectal probe may have distorted pelvic tissues during MRI scanning, the MRI coil was 1.5 Tesla and the study population size was small. However, prospective data collection, blinded measurements by two trained readers and rigorous statistical analysis should be considered strengths. Of note, there was a high MRI inter-rater kappa agreement, which validates the precision of the results. Defining why continent patients after RP suffer from climacturia is challenging. From this analysis climacturia seems to be associated with the presence of a wider urethra, possibly mediated by lower urethral pressures.

CONCLUSION

Although the pathophysiology of climacturia is still not completely elucidated, based on our data, urethral anatomy appears to play a role in its development after RP.