The Triple Clinicopathologic Features to Seminal Vesicle-Sparing Radical Prostatectomy

Abstract

Background and Purpose:

With the widespread early detection programs for prostate cancer, there has been a downward stage migration and a marked decrease in the percentage of men with seminal vesicle invasion (SVI) compared with previous data. We evaluated clinicopathologic findings that are associated with SVI to select patients for potential seminal vesicle-sparing surgery.

Patients and Methods:

We reviewed our radical prostatectomy database from 1997 to 2006 to evaluate the incidence and clinical correlates of SVI. Variables analyzed included serum prostate-specific antigen (PSA) level, clinical stage, percentage of positive cores with cancer, Gleason score on biopsy, age, prostate weight, and urethral and vesical surgical margins. Statistical analysis included univariate and multivariate logistic regressions.

Results:

Of 267 patients, 32 (12%) had SVI. Preoperative PSA level, biopsy Gleason score, and percentage of positive cores were highly predictive of SVI on multivariate analysis. SVI was present in only 1/98 patients (1.02 %) with biopsy Gleason score ≤6, 0/23 patients (0%) with serum PSA level <4 ng/mL, and only 1 patient with ≤12.8% of positive cores on biopsy. In all cases of distal SVI, there was proximal involvement.

Conclusion:

Serum PSA level, Gleason score, and percentage of positive cores on biopsy are statistically significant predictors of SVI on multivariate analysis. Seminal vesiculectomy does not benefit almost 99% of patients with biopsy Gleason score ≤6, PSA level <4 ng/mL, and with <12% cores with cancer. In cases of seminal vesicle-sparing surgery, frozen section of the proximal portion may be of adjunct usefulness for the triple.

Introduction

S ince its original description by Young,¹ the classic technique of radical prostatectomy includes total en bloc removal of the prostatectomy specimen, including the entire seminal vesicles. Earlier studies showed seminal invasion rates of 19% to 26%.²

With the widespread early detection programs for prostate cancer with the advent of prostate-specific antigen (PSA) screening, there has been a downward stage migration and a marked decrease in the percentage of men with seminal vesicle invasion (SVI)—as low as 3% to 5% in some series.³ As a consequence, today most patients who are undergoing radical prostatectomy do not have involvement of seminal vesicles, and their resection may be unnecessary in more than 90% of cases.⁴

The potential interest in preserving seminal vesicles during radical prostatectomy is to improve continence and potency because of the very close relationships between the seminal vesicle, arterial supply of the bladder base, and proximal neurovascular bundles. The motor and sensory components of the pelvic nerve are anatomically located in intimate contact with the tip of the seminal vesicles (3–10 mm).^5,6 Dissection of the seminal vesicle during radical prostatectomy can damage the pelvic plexus, compromising the innervation of the trigone, bladder neck, and posterior urethra, which may adversely affect continence and erectile function.⁷ The risk of injuries to the pelvic plexus can be reduced either by using the cleavage plane between the pelvic plexus and seminal vesicle or by leaving a layer of the seminal vesicle when oncologic conditions allow.

For many years, radiotherapists have excluded the seminal vesicle from their clinical target volume in cases of low-risk prostate cancer because its inclusion increases the rectal dose by about 50% with adverse consequences. Preoperative serum PSA levels, Gleason score, and percentage of positive cores with cancer on needle biopsy are variables that are effectively used to define subgroups of patients in whom seminal vesicle irradiation can be avoided during radiotherapy.⁸ In contrast, seminal vesicles are routinely removed in every radical prostatectomy, even in cases of low-risk prostate cancer. The preoperative identification of cases with low risk for involvement of seminal vesicle might select cases for surgery with preservation of seminal vesicles, potentially decreasing postoperative morbidity and improving the quality of life of these patients while maintaining a complete oncologic resection.

We determined the probability of involvement of the seminal vesicles considering several preoperative variables (serum PSA level, Gleason score on biopsy, clinical stage and percentage of positive cores with cancer on biopsy), and studied the site of involvement of the seminal vesicles.

Patients and Methods

During the period 1997 to 2006, a total of 267 patients with clinically localized prostate cancer underwent radical prostatectomy. All clinical and pathologic data were prospectively collected in our database after Institutional Review Board (ethical committee) approval and written informed consent. Preoperative variables analyzed were serum PSA level, clinical stage, the percentage of positive cores with cancer on biopsy, Gleason score on biopsy, age, and prostate weight. Postoperative variables analyzed included urethral and vesical margins. Total PSA was measured using the previously validated Immulite® PSA kit, and the preoperative serum PSA level was categorized as 0 to 4.0 ng/mL, 4.1 to 10.0 ng/mL, and >10.0 ng/mL. The Gleason score was categorized as 2 to 6, 7, and 8 to 10.

The percentage of positive cores was defined as the number of cores with cancer divided by the total number of cores on transrectal ultrasonography guided systematic 12-core biopsy performed by a single sonographer using a biplanar technique with a 7.5 MHz probe (Toshiba SSA-250-A, Toshiba, Tokyo, Japan) with patients in the left lateral decubitus position. Automated biopsy gun and an 18-gauge needle were used, and all patients received 500 mg ciprofloxacin twice a day for 5 days starting from the day before the biopsy.

The clinical stage was analyzed by digital rectal examination (nonpalpable tumor–T₁; palpable tumor–T₂). All these variables were related to the involvement of the seminal vesicles in the surgical specimen. The same pathologist has evaluated all biopsy and pathologic specimens.

The association of seminal vesicle invasion with each of the clinical and biopsy features was assessed by the Fisher exact test and the chi-square test. Logistic regression was used to evaluate the contribution of age, preoperative serum PSA level, biopsy Gleason score, clinical stage, and percent of positive cores to the risk of SVI. Continuous variables were compared using the Mann-Whitney nonparametric test. A P value ≤0.05 was considered statistically significant. The SAS System for Windows (SAS Institute Inc, 2002–2003, Cary, NC) was used for data processing.

Results

Of 267 patients, 32 (12%) had SVI (Table 1). Preoperative PSA level, biopsy Gleason score, and percentage of positive cores were highly predictive of SVI on multivariate analysis. SVI was present in only 1/98 patients (1.02%) with biopsy Gleason score ≤6, 0/23 patients (0%) with serum PSA level <4 ng/mL, and only 1 patient with ≤12.8% of positive cores on biopsy.

Table 1.

Clinicopathologic Findings of Patients With and Without Seminal Vesicle Invasion

Findings	SVI	No SVI	P value
Number of patients	32 (12%)	235 (88%)
Mean age (SD)	63.50 (6.01)	63.44 (6.55)	0.7067
PSA ng/mL
<4	0 (0%)	23 (9.83%)	0.0246
4–10	14 (43.75%)	130 (55.56%)
>10	18 (56.25%)	81 (34.61%)
Mean PSA (SD)	14.56 (10.61)	9.25 (5.58)	0.0008
Biopsy Gleason score
≤6	1 (3.12%)	97 (41.28%)	0.0001
7	21 (65.62%)	134 (57.02%)
≥8	10 (31.26%)	4 (1.70%)
Mean Gleason (SD)	7.47 (0.84)	6.54 (0.69)	0.0001
Clinical stage
Palpable tumor	22 (73.33%)	125 (54.83%)	0.0542
Nonpalpable tumor	8 (26.67%)	103 (45.17%)
Mean % of positive cores on biopsy (SD)	33.86 (22.84)	12.25 (10.71)	0.0001
Vesical surgical margins
Negative	25/246 (78.12%)	221/246 (96.09%)
Positive	7/16 (21.88%)	9/16 (3.91%)
Urethral surgical margins
Negative	22/232 (68.75%)	210/232 (90.91%)
Positive	10/31 (31.25 %)	21/31 (9.09%)

SVI = seminal vesicle invasion; SD = standard deviation; PSA = prostate-specific antigen.

Table 2 shows the univariate logistic regression analysis of several clinicopathologic variables predictive of SVI.

Table 2.

Univariate Logistic Regression Analysis of Several Clinicopathologic Variables Predictive of Seminal Vesicle Invasion

Variables	N	Estimated parameter	P value	Odds	CI 95%
Age	267	0.0014	0.9597	1.001	0.946–1.060
Clinical stage (T₁ vs T₂)	258	0.8180	0.0593	2.266	0.968–5.303
PSA	266	0.0916	0.0002	1.096	1.044–1.151
Prostate weight	252	−0.0060	0.6265	0.994	0.970–1.018
% of positive cores	236	0.0842	0.0001	1.088	1.054–1.123
Gleason score	267	1.8941	0.0001	6.647	3.171–13.931
<7 vs 7	267	−2.7214	0.0084	0.066	0.009–0.497
>7 vs 7		2.7696	0.0001	15.952	4.582–55.537
Vesical margin (+ vs −)	262	1.9280	0.0004	6.876	2.356–20.061
Urethral margin (+ vs −)	263	1.5143	0.0007	4.546	1.901–10.870

CI = confidence interval; PSA = prostate-specific antigen.

Having made the analysis of logistic regression, we used the stepwise procedure to find the variables with independent significant prediction of SVI (multivariate analysis). With this procedure, we obtained the model shown in Table 3.

Table 3.

Multivariate Logistic Regression Analysis of Variables Predictive of Seminal Vesicle Invasion

Variables	Estimated parameter	P value	Odds	CI 95%
Intercept	−15.1245	0.0001	—	—
% of positive cores	0.0578	0.0019	1.060	1.022–1.099
Urethral margin (+ vs −)	1.2555	0.0400	3.510	1.059–11.635
Gleason score	1.6501	0.0002	5.208	2.211–12.266

CI = confidence interval.

The site of SVI was as follows: Proximal portion of right seminal vesicle in 19 (7.12%) patients and left side in 27 (10.15 %) patients; medial portion of right seminal vesicle in 7 (2.67%) and left side in 16 (6.13%); and, distal portion of right seminal vesicle in 6 (2.3%) and left side in 5 (1.92%) patients. In all cases of distal SVI, there was proximal involvement.

Table 4 shows the triple algorithm that can be useful to select patients for seminal vesicle-sparing surgery.

Table 4.

Triple Clinicopathologic Findings with Least Probability of Seminal Vesicle Invasion

Findings	Seminal vesicle invasion
Preoperative serum PSA <4 ng/mL	0%
Gleason score ≤6 on biopsy	1.02%
Percentage of positive cores on biopsy ≤12%	0%

PSA = prostate-specific antigen.

Discussion

It is a great challenge to detect SVI by any imaging method (CT, transrectal echography, or MRI) because of anatomic complexity and variability among patients.⁹ As a result, attempts have been made to identify patients with SVI preoperatively using nomograms that combine multiple preoperative findings.

Once vesical and urethral margin statuses are postoperatively known, they are not suitable to predict patients to receive seminal vesicle-sparing surgery. Thus the proposed triple was studied among those clinicopathologic features that were obtained before surgery.

In most studies, preoperative serum PSA level, biopsy Gleason score, and percentage of positive cores were all highly predictive of SVI on multivariate analysis.^4,10

–14 Clinical stage and percentage of positive cores at the base of the prostate were also associated with SVI.¹⁰

There is no consensus on the cut point of these variables to predict SVI. Guzzo and associates¹³ proposed a categorization of patients based on negative digital rectal examination, low serum PSA level (<7 ng/mL), and percentage of positive cores on biopsy (less than 17%) to define a patient who was electable for a seminal vesicle-sparing surgery.

Cut points of serum PSA <10 ng/mL, Gleason score <7, and percentage of cores with cancer <50% were predictive of 5% of SVI.⁴ This model was tested by others in 1406 men who underwent radical prostatectomy and seminal vesicle removal between 1998 and 2004 to determine its validation.¹⁴ The authors found 90% sensitivity but only 50% specificity. They concluded that the algorithm should not be used to select patients for seminal vesicle-sparing during radical prostatectomy. Nevertheless, the same algorithm could be helpful in patients who undergo external beam radiation therapy. This discrepancy occurs because the balance between the benefit of avoiding unnecessary treatment and the harm differs between radiotherapy and surgery.

Dall'Oglio and colleagues¹¹ found on multivariate analysis that serum PSA level ≤4 ng/mL, Gleason score 2 to 6, and <25% cores with cancer on biopsy were predictive of no SVI. Gofrit and coworkers¹² in a study with 1003 patients observed that in patients with biopsy Gleason score ≤6 and serum PSA level <4.3 ng/mL, the risk of SVI was zero. In contrast, in cases of biopsy Gleason score >6, serum PSA level ≥7.7 ng/mL, and percentage of positive cores >89%, the risk of SVI was 78%.

Based on our results, we propose for indication of seminal vesicle-sparing surgery an algorithm including triple clinicopathologic findings with the least probability of SVI (Table 4). In our study, no patient had SVI with preoperative serum PSA level <4 ng/mL, only 1 patient with Gleason score ≤6 on the needle biopsy, and only 1 patient with percentage ≤12.8% of cores with cancer. Patients selected with these cut points have a very low probability of SVI. Almost 99% of the patients with biopsy Gleason score ≤6, serum PSA level <4 ng/mL, and <12% positive cores with cancer may have no benefit with seminal vesiculectomy.

While there is approximately 30% upgrading of Gleason score 6 prostate cancers on biopsy after prostatectomy, hardly any have SVI with the proposed criteria. The triple restrictive aspect is in part because of the sampling error associated with prostate biopsy.¹⁰

The percentage of patients who actually have all three of these factors (Gleason 6, PSA level <4 ng/mL, and <12.8% positive cores) was 10% in this study, and it was previously described as being around 10% to 30 %.³ Considering that all three of these factors are proposed concomitantly for the first time, however, there is no previous specific data that focus on them.

The question of overdiagnosis and overtreatment is a very important issue in prostate cancer, and it is noteworthy that active surveillance must be offered to patients who present the proposed criteria once they are classified as having low-risk prostate cancer. Vesicle-sparing prostatectomy could be an alternative to classic radical prostatectomy to those who desire surgery, equalizing to radiotherapy results. In view of the heterogeneous aspect of prostate cancer, the optimal management ranges from radical to no treatment and is case specific, going all the way through fit treatments. A progressively less morbid and in shape treatment/surgery in well-selected cases is warranted.

There are isolated series of patients who underwent seminal vesicle sparing-prostatectomy showing that the outcomes for urinary and erectile function have been better than expected. Seminal vesicle-sparing radical prostatectomy was reported by John and Hauri.⁷ In a prospective study with 54 patients, 34 patients underwent standard radical retropubic prostatectomy while 20 underwent seminal vesicle tip-sparing surgery. The patients in the group of seminal vesicle sparing-surgery had significantly higher continence rates postoperatively (60% after 6 weeks and 95% after 6 months vs 18% and 82% in the group who underwent standard surgery).

Others series of seminal vesicle-sparing radical prostatectomy showed good feasibility and improved early postoperative urinary continence, erectile function, quality of orgasm, and sexual performance, all these related to quality of life, without compromised cancer control.^15
–17 A series including patients who underwent radical perineal prostatectomy, with more than 350 patients in the seminal vesicle-sparing group, showed that leaving the seminal vesicle in situ did not result in increased PSA relapse rates.¹⁵

Moreover, large prospective studies that are designed to evaluate PSA and clinical progression are lacking, as well as specific and overall mortality in patients who are treated with seminal vesicle-sparing surgery. A prospective trial may be not feasible, however, considering that a trial planning to show that seminal vesicle-sparing surgery improves function but does not increase the recurrence rate by more than 2% might well require more than 10,000 patients.¹⁵

The estimated percentage of patients with prostate cancer progression as a result of cancer remaining in the seminal vesicle because of a limited resection of the gland was estimated to be only 0.3%, based on results of large retrospective studies. When in doubt of SVI, a frozen section could be useful to rule out this occurrence during surgery.⁷

Although the seminal vesicles produce PSA, the PSA derived from the remaining seminal vesicle tips after seminal vesicle-sparing radical prostatectomy has no effect on the oncologic follow-up of these patients. An elevated PSA level detected by current PSA tests after sparing surgery is not caused by the remaining seminal vesicle tips but rather indicates the presence of residual prostatic tissue or cancer micrometastases.¹⁷

The frequency of prostate cancer extension into the distal 1 cm of seminal vesicles was studied by Korman and colleagues.¹⁸ In 71 patients who were undergoing radical prostatectomy, no tumor was found in the distal 1 cm of the seminal vesicle, including 12 patients with proximal invasion. If dissection of the seminal vesicle is difficult and a small fragment is left behind, the prognosis is unlikely to be altered.¹⁸

The most important and most frequent route of SVI is extraprostatic extension of prostate carcinoma into the soft tissue adjacent to the ipsilateral seminal vesicle and then into the wall of the seminal vesicle (68%). The second most common route is via the sheath of the ejaculatory duct (21%).¹⁹ In our study, all cases of distal involvement of the seminal vesicle had proximal involvement. Therefore, in cases of seminal vesicle-sparing surgery, a frozen section of the proximal portion may be of adjunct usefulness for the proposed triple algorithm.

It is worth mentioning the comparison with sparing of seminal vesicles during radiotherapy. Pretreatment variables (serum PSA levels, Gleason score, and percentage of positive cores) are used to define subgroups of patients in whom seminal vesicle irradiation can be avoided during radiotherapy. The irradiation of the seminal vesicles is only included for intermediate- and high-risk patients (serum PSA level >10 ng/mL, biopsy Gleason score >7, or clinical stage >T_2b).⁸

Conventional external beam radiation therapy directed to the prostate alone resulted in 5-year PSA failure-free survival rates equivalent to surgery on retrospective comparison in patients with clinical stage T₁ to T_2a, PSA level ≤10 ng/mL, and biopsy Gleason score ≤6 prostate cancer.²⁰ Considering that for patients who are classified as low risk for progression, the radiotherapy is as effective as radical prostatectomy, patients in this condition who undergo radical prostatectomy, including complete seminal vesicle resection, may be overtreated.

A article limitation is the relatively small number of patients who were analyzed and that the proposed triple should be tested in future multicentric study protocols that include a large number of patients before advocating widespread use of such an approach.

Conclusions

In accordance with other studies, our results showed that preoperative serum PSA level, Gleason score on the biopsy, and percentage of positive cores with cancer are statistically significant predictors of SVI on multivariate analysis.

Due to a very low probability of seminal vesicle invasion, almost 99% of the patients presenting the triple: biopsy Gleason score ≤6, serum PSA <4 ng/mL and <12% positive cores with cancer may have no benefit with seminal vesiculectomy. All cases of distal involvement of the seminal vesicle had also proximal invasion. Therefore, a frozen section of the proximal portion of the seminal vesicle may have an adjunct usefulness. Seminal vesicle-sparing radical prostatectomy may be a surgical option to preserve pelvic innervation, maintaining urinary continence and potency in selected patients.

Nevertheless, further and larger series are necessary to confirm these results once seminal vesicle sparing is a continuing trend at the current scenario of disseminated prostate cancer screening with consequently diagnosis migration to early stage disease.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

Young

. The early diagnosis and radical cure of carcinoma of the prostate. Being a study of 40 cases and presentation of a radical operation which was carried out in four cases. 1905. J Urol, 2002; 167:939–947.

Villers

, McNeal

, Redwine

et al. Pathogenesis and biological significance of seminal vesicle invasion in prostatic adenocarcinoma. J Urol, 1990; 143:1183–1187.

Han

, Partin

, Chan

, Walsh

. An evaluation of the decreasing incidence of positive surgical margins in a large retropubic prostatectomy series. J Urol, 2004; 171:23–26.

Zlotta

, Roumeguère

, Ravery

et al. Is seminal vesicle ablation mandatory for all patients undergoing radical prostatectomy? A multivariate analysis on 1283 patients. Eur Urol, 2004; 46:42–49.

Tewari

, Takenaka

, Mtui

et al. The proximal neurovascular plate and the tri-zonal neural architecture around the prostate gland: Importance in the athermal robotic technique of nerve-sparing prostatectomy. BJU Int, 2006; 98:314–323.

Walz

, Graefen

, Huland

. Basic principles of anatomy for optimal surgical treatment of prostate cancer. World J Urol, 2007; 25:31–38.

John

, Hauri

. Seminal vesicle-sparing radical prostatectomy: A novel concept to restore early urinary continence. Urology, 2000; 55:820–824.

Katcher

, Kupelian

, Zippe

et al. Indications for excluding the seminal vesicles when treating clinically localized prostatic adenocarcinoma with radiotherapy alone. Int J Radiat Oncol Biol Phys, 1997; 37:871–876.

Sala

, Akin

, Moskowitz

et al. Endorectal MR imaging in the evaluation of seminal vesicle invasion: Diagnostic accuracy and multivariate feature analysis. Radiology, 2006; 238:929–937.

10.

Koh

, Kattan

, Scardino

et al. A nomogram to predict seminal vesicle invasion by the extent and location of cancer in systematic biopsy results. J Urol, 2003; 170:1203–1208.

11.

Dall'Oglio

, Sant'Anna

, Antunes

et al. Analysis of risk factors of involvement of seminal vesicles in patients with prostate cancer undergoing radical prostatectomy. Int Braz J Urol, 2004; 30:472–478.

12.

Gofrit

, Zorn

, Shikanov

et al.

Is seminal vesiculectomy necessary in all patients with biopsy Gleason score 6?

J Endourol, 2009; 23:709–713.

13.

Guzzo

, Vira

, Wang

et al. Preoperative parameters, including percent positive biopsy, in predicting seminal vesicle involvement in patients with prostate cancer. J Urol, 2006; 175:518–522.

14.

Secin

, Bianco

, Cronin

et al. Is it necessary to remove the seminal vesicles completely at radical prostatectomy? Decision curve analysis of European Society of Urologic Oncology criteria. J Urol, 2009; 181:609–614.

15.

Albers

, Schäfers

, Löhmer

, de Geeter

. Seminal vesicle-sparing perineal radical prostatectomy improves early functional results in patients with low-risk prostate cancer. BJU Int, 2007; 100:1050–1054.

16.

Sanda

, Dunn

, Wei

et al. Seminal vesicle sparing technique is associated with improved sexual HRQOL outcome after radical prostatectomy. J Urol, 2002; 167Abstract 606.

17.

John

, Hauri

, Maake

. The effect of seminal vesicle-sparing radical prostatectomy on serum prostate-specific antigen level. BJU Int, 2003; 92:920–923.

18.

Korman

, Watson

, Civantos

et al.

Radical prostatectomy: Is complete resection of the seminal vesicles really necessary?

J Urol, 1996; 156:1081–1083.

19.

Billis

, Teixeira

, Stelini

et al.

Seminal vesicle invasion in radical prostatectomies: Which is the most common route of invasion?

Int Urol Nephrol, 2007; 39:1097–1102.

20.

D'Amico

, Whittington

, Kaplan

. Equivalent 5-year bNED in select prostate cancer patients managed with surgery or radiation therapy despite exclusion of the seminal vesicles from the CTV. Int J Radiat Oncol Biol Phys, 1997; 39:335–340.