Japanese Journal of Clinical Oncology

Figure 1. Recovery of urinary continence following radical prostatectomy. Numbers of patients under observation are indicated in parentheses.

For radical prostatectomy, the retropubic approach of Walsh (1) was used with some modification in all but one patient, who had undergone antegrade prostatectomy. Lymphadenectomy was limited to the bilateral obturator nodes. The author's procedure for apical dissection is as follows: after dividing with careful precision the puboprostatic ligament, the lateral pelvic fascia is perforated using a right-angle clamp with a long beak and the clamp is passed through the avascular plane between the anterior surface of the urethra and posterior surface of the dorsal vein complex. The clamp is used to grasp a 22-gauge steel wire, which is brought beneath the dorsal vein complex. This complex is then transected with a No.15 blade knife, cutting as the wire is pulled up toward the head. The wire serves as a template, by which the prostatic apex is protected and the dorsal vein complex can be evenly divided. The distal edge of the complex is oversewn horizontally using continuous 3-0 polyglactin absorbable suture. The urethra is then divided 2-3 mm distal to the apex of the prostate, followed by transection of the residual lateral and posterior components of the striated urethral sphincter. Bladder neck reconstruction with `tubularized neourethra formation' rather than `tennis racket closure' was carried out as described by Steiner et al. (7) on 11 patients. Eighty operations were conducted by the same surgeon (author S.E.). Four other doctors performed 14 operations under the supervision of the author. Serum PSA was determined up to March 1993 using the Eiken polyclonal radioimmunoassay (Eiken, Tokyo; 33 patients), and using the Dainapack IMx PSA (Dinabot, Tokyo, 61 patients) thereafter. Frozen serum samples kept at -80^oC were analyzed for preoperative data with IMx PSA in 28 patients. For uniformity, Eiken PSA data for the other 5 patients were interconverted, as recommended by Machida et al (8), as follows: IMx PSA = (1.39 * Eiken PSA) - 1.02.

Radical prostatectomy specimens were examined by whole organ step-section techniques in all but two cases, as described previously (9). Random multiple sectioning, stained with hematoxylin and eosin, was done on two patients. Tumor grade and depth of capsular penetration were determined. A search for and assessment of seminal vesicle invasion, tumor extension to the surgical margin and the presence of nodal metastasis was carried out. Tumor volume was measured as described previously (9).

Neoadjuvant endocrine therapy prior to surgery is not conducted at our institution. External beam radiation was delivered to the prostatic fossa and periprostatic tissue via a linear accelerator for detectable PSA following radical prostatectomy. In all instances, the beam was directed to the pelvis by a 4-field technique at an absorption dose of 46 to 50 Gy followed by a boost to the anastomosis site by multiple fields at a total dose of 56-60 Gy. Treatment was conducted in five fractions per week at 2.0 Gy/ fraction. No preoperative urodynamic study was conducted on any of the patients.

The criteria of Catalona and Basler (10) were used as a basis for indication of urinary continence. Briefly, continent patients were considered to be those not requiring a pad to keep the clothing dry, and those who with severe abdominal straining occasionally leaked 1 or 2 drops of urine. We considered men with stress incontinence requiring a pad to be incontinent. Total incontinence was defined as absence of urinary control when standing. Urinary continence could not be assessed in one patient with stage T1a disease owing to prolonged catheterization following meticillin-resistant Staphylococcus aureus-induced septicemia and cerebral damage. All patients were seen once every two weeks for the first three months after surgery, quarterly for the first year and biannually for two years, and yearly thereafter. Each follow-up required a history statement, physical examination and serum PSA examination. For those requiring more than 2 pads per day at 12 months after surgery owing to stress incontinence, 60 µg clenbuterol hydrochloride was usually prescribed three times daily. For patients showing little or no improvement, anticholinergic therapy was attempted with 9 mg oxybutynin hydrochloride three times daily or propiverine hydrochloride 20 mg once daily. For persistent serious incontinence, 25 mg imipramine hydrochloride was administered in addition three times daily.

Backward stepwise logistic regression analysis was conducted to determine the impact of perioperative variables on the recovery of urinary continence following surgery. The logistic regression model in this study included age at surgery, preoperative endocrine therapy, preoperative PSA, methods of bladder neck reconstruction, internal urethrotomy for anastomotic stricture, adjuvant external beam radiation therapy for postoperative PSA elevation, clinical stage, pathologic stage, tumor grade, total tumor volume and the preservation of neurovascular bundles.

RESULTS

Mean subject age was 63.5 years (range 49-73 years). The mean follow-up period for 94 patients was 22.3 months (range 0.9-51.4 months). The 92 cancers were classified clinically as stages T1a in 2 patients, T1b in 4, T1c in 26, T2a in 10, T2b in 18, T2c in 10, T3a in 3, T3b in 3, T3c in 15 and T4a in 1 patient. Endocrine therapy had been conducted in 9 patients preoperatively. Three of these patients were referrals from other hospitals and had been given neoadjuvant endocrine therapy using luteinizing hormone-releasing hormone agonist and flutamide for 3 months prior to surgery. The other 6 patients underwent prostatectomy for local progression following primary endocrine therapy. No patient was incontinent preoperatively.

Table 1 . Urinary continence following radical prostatectomy according to preoperative endocrine therapy

Months following	No endocrine therapy (n = 85)			Endocrine therapy (n = 9)
prostatectomy	Continence No. (%)	Incontinence No. (%)	Unknown No. (%)	Continence No. (%)	Incontinence No. (%)	Unknown No. (%)
1	17 (20.0)	66 (77.6)	2 (2.4)	1 (11.1)	7 (77.8)	1 (11.1)
3	42 (51.2)	39 (47.6)	1 (1.2)	1 (12.5)	6 (75.0)	1 (12.5)
6	55 (71.4)	21 (27.3)	1 (1.3)	2 (28.6)	5 (71.4)	0 (0.0)
12	50 (74.6)	16 (23.9)	1 (1.5)	2 (28.6)	5 (71.4)	0 (0.0)
18	44 (78.6)	11 (19.6)	1 (1.8)	2 (28.6)	5 (71.4)	0 (0.0)
24	36 (78.3)	9 (19.6)	1 (2.2)	2 (33.3)	4 (66.7)	0 (0.0)
30	21 (72.4)	7 (24.1)	1 (3.4)	2 (33.3)	4 (66.7)	0 (0.0)
36	11 (78.6)	2 (14.3)	1 (7.1)	2 (50.0)	2 (50.0)	0 (0.0)
42	9 (100.0)	0 (0.0)	0 (0.0)	0 (0.0)	2 (100.0)	0 (0.0)
48	3 (100.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (100.0)	0 (0.0)

Table 2 . Urinary continence following radical prostatectomy according to preoperative PSA levels

Months following	Preop. PSA <10.0 ng/ml (n = 58)			Preop. PSA >= 10.0 ng/ml (n = 36)
prostatectomy	Continence No. (%)	Incontinence No. (%)<	Unknown No. (%)	Continence No. (%)	Incontinence No. (%)	Unknown No. (%)
1	14 (24.1)	42 (72.4)	2 (3.4)	4 (11.1)	31 (86.1)	1 (2.8)
3	29 (52.7)	26 (47.3)	0 (0.0)	14 (40.0)	19 (54.3)	2 (5.7)
6	39 (78.0)	11 (22.0)	0 (0.0)	18 (52.9)	15 (44.1)	1 (2.9)
12	36 (81.8)	8 (18.2)	0 (0.0)	16 (53.3)	13 (43.3)	1 (3.3)
18	32 (84.2)	6 (15.8)	0 (0.0)	14 (56.0)	10 (40.0)	1 (4.0)
24	27 (87.1)	4 (12.9)	0 (0.0)	11 (52.4)	9 (42.9)	1 (4.8)
30	17 (81.0)	4 (19.0)	0 (0.0)	6 (42.9)	7 (50.0)	1 (7.1)
36	9 (90.0)	1 (10.0)	0 (0.0)	4 (50.0)	3 (37.5)	1 (12.5)
42	6 (100.0)	0 (0.0)	0 (0.0)	3 (60.0)	2 (40.0)	0 (0.0)
48	1 (100.0)	0 (0.0)	0 (0.0)	2 (66.7)	1 (33.3)	0 (0.0)

Preoperative PSA averaged 14.8 ± 21.2 (standard deviation) ng/ml, 5.6 ± 6.5 ng/ml for those with and 15.7 ± 22.0 ng/ml for those without preoperative endocrine therapy. Total tumor volume averaged 8.4 ± 10.5 ml (range 0.07-59.9 ml ), 18.4 ± 17.5 ml for those with and 7.5 ± 8.8 ml for those without preoperative endocrine therapy. Overall, 36 (39.1%, 36/92) had organ-confined disease pathologically: one of nine (11.1%) of those with and 35 of 83 (42.2%) of those without preoperative endocrine therapy. Tumor grade was classified postoperatively as well differentiated (Gleason sum 2-4) or moderately differentiated (Gleason sum 5 or 6) in 16 (17.6%) or 21 (23.1%) patients respectively. Twenty-eight (30.7%) and 26 (28.6%) patients had poorly differentiated tumors with Gleason sums of 7 and 8-10 respectively.

Seventeen (18.1%) patients developed anastomotic stricture requiring internal urethrotomy at an average of 9.0 ± 6.1 months after surgery (range 2.5-22.3 months). Eighteen patients underwent radiation therapy because of postoperative elevation of the PSA level. Average time to radiation following prostatectomy was 12.3 months (range 3.4 to 35.2), and an average dose of 57.7 ± 2.2 Gy was delivered.

Hemi- and bilateral neurovascular bundles were preserved in 35 and 32 patients respectively. Bilateral neurovascular bundles were sacrificed in the other patients.

Urinary continence had recovered in 19.1% of the patients at 1 month, 47.8% at 3 months, 67.9% at 6 months, 70.3% at 12 months, 73.0% at 18 months, 73.1% at 24 months, 65.7% at 30 months and 72.2% at 36 months postoperatively (Fig. 1, Tables 1-3). The interval to recovery of urinary continence averaged 4.0 ± 3.3 months (range 1-18 months). There was no totally incontinent patient. Two of the 16 incontinent men required >5 pads a day owing to severe stress incontinence at 18 months after surgery. One of these patients complained of limited daily living activity. The others had stress incontinence requiring 1 pad (11 patients) or 2-3 pads (three patients) per day. None of the five patients administered medication regained urinary continence. One of three patients with no invasive tumor in the removed specimen remained incontinent at 24 months following surgery. The other two patients regained continence at 3 months postoperatively. To predict urinary continence following radical prostatectomy, backward stepwise logistic regression analysis indicated that preoperative endocrine therapy, the preoperative PSA level and the age at surgery were significant covariates (Table 4). Preoperative endocrine therapy, a preoperative PSA level of 10.0 ng/ml and age <70 years at the time of surgery were all associated with higher probability of urinary incontinence (Tables 1-3).

DISCUSSION

One of the major disadvantages of radical prostatectomy is incontinence. In most large series, figures of total incontinence are low (<5%), 70-96% of patients being considered continent at month 18 (10-20). However, results obtained in community practice may be less optimistic. In a retrospective study using Medicare/Medicaid files, 63% of patients complained of some incontinence, 31% needed a permanent appliance and 43% complained of stress incontinence (12). A recent university-based prospective study has shown the effects of radical prostatectomy to be worse when reported by patients than when published by urologists (15). Of the 86 patients who responded, 47% used a pad and 59% leaked urine daily, 34% finding their incontinence bothersome. It is thus of the utmost importance to assess the recovery rates of urinary continence at each individual institution in order to state this information clearly and honestly for this major form of surgery, rather than quoting figures from large institutions.

Though the precise mechanisms are unclear, many factors have been shown to be involved in the etiology of postprostatectomy incontinence (2-5). These include abnormal bladder function, such as decreased compliance and/or detrusor instability, previous prostatic surgery and a damaged sphincteric mechanism, and damage to the pelvic diaphragm musculature and innervation (2-5). Urodynamic studies indicate that urethral and detrusor instability is correlated poorly with incontinence (3). Continence after radical prostatectomy is also dependent on sphincteric efficiency, which may be influenced by the anatomical configuration of the reconstructed bladder outlet and integrity of the distal urethral sphincteric mechanism. Prior open prostatectomy or transurethral resection of the prostate has no influence on the resumption of urinary control, nor has pathologic stage, preservation of neurovascular bundles or prostate weight (10,11,13,14). Age adversely affects the recovery of urinary continence in some patients (11,14), but not in others (10,13).

In this study, postoperative recovery of urinary continence continued for up to 18 months and then plateaued (Figure 1). No pads were required in 73.1% of the patients. Our results are less satisfactory than those reported in the world literature (10-20). The inclusion of many men with clinically advanced prostate cancer in our study would not account for this finding, since no statistically significant relationship was demonstrated. Preoperative endocrine therapy, a preoperative PSA level of >= 10.0 ng/ml and an age at surgery of <70 years were all independently associated with a higher probability of urinary incontinence. Only 30% of patients given preoperative endocrine therapy were continent at 18 months after surgery, while 80% recovered continence without endocrine therapy (Table 1). The etiology of these findings is not entirely clear. Most of the patients had pathologically advanced disease. Sphincteric damage associated with dissection of large, more advanced tumors may be one causative factor. Fibrosis around the apex following endocrine therapy may make surgical resection more technically demanding. Accordingly, functional urethral length as well as the innervation important for urinary control may be compromised in such patients. Only 56.0% of those with a preoperative PSA level of >= 10.0 ng/ml regained continence by 18 months after surgery, while 84.2% of those with a PSA level of <10.0 ng/ml recovered continence (Table 2). This would indicate that more advanced cancers have a less satisfactory outcome in terms of recovery of urinary continence, though this was not confirmed in the clinical and pathological stages of the present study (P > 0.05, Table 4). The influence of age in this study may have been a result of patient selection (Table 3). Older patients who elected to have radical surgery may have been in better general condition than would be expected for age. None of the remaining perioperative variables including methods of bladder neck reconstruction, internal urethrotomy for anastomotic stricture, adjuvant external beam radiation therapy, tumor grade, total tumor volume or preservation of neurovascular bundles had any significant effect on the recovery of urinary continence (P > 0.05, Table 4).

Men with significant post-prostatectomy incontinence may have a major component of bladder dysfunction contributing to incontinence (5). Anticholinergic therapy in patients with high pressure bladder dysfunction alone may improve continence significantly, but this was not observed in the present patients. Unfortunately, due to lack of data from urodynamic studies on our patients, no definitive conclusion is possible at this time. One patient who required more than 5 pads per day complained of limited daily activity on account of urinary incontinence. The design of the present study did not permit the assessment of data regarding patient performance status to an adequate degree.

Table 3 . Urinary continence following radical prostatectomy according to age at surgery

Months	<70 years old (n = 82)			>= 70 years old (n = 12)
following prostatectomy	Continence No. (%)	Incontinence No. (%)	Unknown No. (%)	Continence No. (%)	Incontinence No. (%)	Unknown No. (%)
1	16 (19.5)	64 (78.1)	2 (2.4)	2 (16.7)	9 (75.0)	1 (8.3)
3	40 (49.4)	40 (49.4)	1 (1.2)	3 (33.3)	5 (55.6)	1 (11.1)
6	52 (68.4)	24 (31.6)	0 (0.0)	5 (62.5)	2 (25.0)	1 (12.5)
12	47 (71.2)	19 (28.8)	0 (0.0)	5 (62.5)	2 (25.0)	1 (12.5)
18	41 (73.2)	15 (26.8)	0 (0.0)	5 (71.4)	1 (14.3)	1 (14.3)
24	33 (71.7)	13 (28.3)	0 (0.0)	5 (83.3)	0 (0.0)	1 (16.7)
30	18 (62.1)	11 (37.9)	0 (0.0)	5 (83.3)	0 (0.0)	1 (16.7)
36	8 (66.7)	4 (33.3)	0 (0.0)	5 (83.3)	0 (0.0)	1 (16.7)
42	7 (77.8)	2 (22.2)	0 (0.0)	2 (100.0)	0 (0.0)	0 (0.0)
48	2 (66.7)	1 (33.3)	0 (0.0)	1 (100.0)	0 (0.0)	0 (0.0)

Table 4 . Results of multivariate analysis for variables that affect urinary continence following radical prostatectomy

Variables	Parameter estimates	Standard error	P value
Preop. endocrine therapy	-1.1918	0.4157	0.0042
Preop. PSA	-0.5780	0.2342	0.0136
Age	0.8209	0.3676	0.0256
Methods of bladder neck reconstruction			0.5335
Internal urethrotomy			0.9149
Adjuvant radiotherapy			0.8917
Clinical stage			0.5597
Pathological stage			0.8749
Tumor grade			0.8117
Total tumor volume			0.7083
Preservation of neurovascular bundles			0.0556

PSA, prostate-specific antigen.

Surgical techniques should be improved to minimize the possibility of urinary incontinence. Gaker et al. described a technique of radical retropubic prostatectomy in which the bladder neck is preserved and the prostatic urethra is dissected free from within the prostate itself (21). With this modification, total continence was achieved immediately after catheter removal in 46% and within 7 weeks in 88% of the patients. Partial rather than complete incision of the puboprostatic ligament helps to preserve the apical anatomical configuration to support the bladder neck, consequently allowing better recovery of urinary continence (16). However, these techniques may jeopardize cancer control owing to incomplete dissection. More experience is needed before these techniques can be recommended. Narayan et al. noted that sphincteric nerve injury contributed to urinary incontinence following prostatectomy. Innervation of the urethral sphincter occurred 0.3-1.3 cm from the prostatic apex, and in 50% of cadavers, only unilaterally or with only one branch on each side. The proximity of these nerves to the prostatic apex makes them susceptible to injury during radical prostatectomy. A thorough understanding of such neuroanatomy may lead to surgical techniques that can avoid urinary incontinence (4).

Postprostatectomy urinary incontinence is multifactorial. To minimize this complication, stricter criteria for the indication of radical prostatectomy are needed when treating patients with prostate cancer. The high incidence of incontinence in those given preoperative endocrine therapy and those with local tumor progression does not justify radical prostatectomy unless a surgical cure is guaranteed. Further efforts should be made to improve overall continence following radical prostatectomy.

ACKNOWLEDGEMENTS

This study was supported in part by a Grant from the Ministry of Health and Welfare of Japan (7-42).

References

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Received September 2, 1996; accepted October 24, 1996
For reprints and all correspondence: Shin Egawa, Department of Urology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228, Japan
Abbreviations: PSA, prostate-specific antigen; AAH, atypical adenomatous hyperplasia.

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