PROSPECTIVE ANALYSIS OF THE BIOCHEMICAL RECURRENCE OF PROSTATE CARCINOMA AFTER PRESERVATION OF THE BLADDER NECK IN RADICAL PROSTATECTOMY
LUCIANO J. NESRALLAH, MIGUEL SROUGI, ADRIANO NESRALLAH, KATIA R. M. LEITE
Division of Urology, Paulista School of Medicine, Federal University of São Paulo, (UNIFESP), São Paulo, SP, Brazil
ABSTRACT
Objectives:
The preservation of the bladder neck in radical prostatectomy has been
supported in literature as an important step in the urinary continence
maintenance. In this prospective study a comparison was made of the urinary
continence rates and neoplasm control based on preservation or resection
of the bladder neck.
Material and Methods: Patients with stage
T1c – T2c prostate adenocarcinoma treated by radical prostatectomy,
were randomized during the surgery, by drawing, either for the bladder
neck preservation or for resection. The continence was evaluated in an
interview 2 days after the Foley catheter removal and in the second and
sixth months after the surgery. The same pathologist examined the surgical
margins systematically. The neoplasm control was assessed by prostate
specific antigen (PSA) dosage in the second month after the surgery and
later, semiannually.
Results: An interim analysis of the first
70 patients, showed a high incidence of exclusively involvement of the
bladder neck surgical margin in the preservation group and, due to this
finding, the study was closed prematurely. Each group was assigned 35
patients but the bladder neck could not be preserved in 4 and 1 died,
leaving 31 in the preservation group and 38 in the resection group. There
was no statistical difference between the 2 groups as to the early or
late urinary incontinence rates. Two days after the catheter removal and
in the second and sixth months after the surgery the respective rates
were: 21%, 13% e 5% in the bladder neck resection group and 32%, 13% e
3% in the bladder neck preservation group. The PSA dosage showed a biochemical
recurrence of the neoplasm (> 0.3 ng/ml) in six of the 30 (20%) patients
submitted to bladder neck preservation and in five of the 33 (15.15%)
patients submitted to bladder neck resection, after a median of 27 months
of follow-up (25 to 30 months). The difference between the two groups
was not statistically significant (p = 0.74).
Conclusions: The bladder neck preservation
in radical prostatectomy does not improve the postoperative continence
rates, shows a tendency to produce more positive surgical margins at the
bladder neck level, but the neoplasm evolution is not different when compared
to patients submitted to bladder neck resection.
Key words:
prostate; prostatic neoplasia; prostatectomy; urinary incontinence
Braz J Urol, 27: 447-453, 2001
INTRODUÇÃO
The
increase of prostate cancer detection in initial stages (T1 – T2)
resulted in a significant increase in the number of radical prostatectomies.
Having as objective the decrease of morbidity related to the surgical
procedure, many researchers are studying procedures to refine the prostatectomy
technique, but always with the concern of not compromising the neoplasm
cure.
The
radical prostatectomy is a procedure associated to undesirable outcome
such as sexual impotence and urinary incontinence. The pioneering studies
of Walsh et al.(1) described precisely the pelvic anatomy of man and allowed
for a surgery performed with smaller risks of sexual impotence and urinary
incontinence, more acceptable by the patients. The surgical technique
described by Walsh includes the bladder neck resection with the prostate
and the seminal vesicles. The author reports that 91% of the treated patients
remain continent and do not use any urinary pad (2).
Moderate
or pronounced urinary incontinence is seen in 2% to 40% (3-6) of the patients
submitted to radical prostatectomy. The lower rates are seen in those
operated by teams that have greater experience with the surgical technique.
The mechanism of continence after prostatectomy has been studied and there
are two functionally independent anatomical structures involved in this
mechanism: the external or distal sphincter and the internal or proximal
sphincter, in the bladder neck.
Several
attempts to improve continence rates after radical prostatectomy, sparing
these anatomical structures have been reported: bladder neck preservation
(7,8); bladder neck tubularization (9,10); puboprostatic ligaments sparing
(11) and careful dissection of the urethra sparing the striated sphincter
(12).
The
bladder neck preservation has been supported as an important maneuver
in the urinary continence maintenance, without compromising the patients
cure rate (7,8).
This
randomized, controlled, double-blind study of patients with a localized
prostate cancer diagnosis was performed to evaluate prospectively the
results of the bladder neck preservation in radical prostatectomies in
what concerns the urinary continence rates, tumor free surgical margins
and the neoplasm control.
MATERIAL AND METHODS
Participants:
All the patients with clinical diagnosis of prostate adenocarcinoma T1
and T2 who were candidates to radical prostatectomy in this institution,
from May to October 1998, participated in this study. Patients with a
previous history of prostate transurethral resection and those with neurogenic
dysfunction of the lower urinary tract were excluded. Two patients stage
T3a who were considered borderline between T2 and T3 were included. All
patients were clinically staged using the TNM classification (13). For
this purpose, the patients were analyzed through digital rectal exam,
prostate specific antigen and total and prostate acid phosphatases dosages
in the serum, bone scan, computerized tomography of the abdomen and chest
X-ray. At the end of the evaluation, forty patients had the disease stage
T1c (57%), thirteen, stage T2a (18%), eight, stage T2b (12%), seven, stage
T2c (10%) and two patients, stage T3a (3%).
The
study was planned to have with 120 patients with prostate adenocarcinoma,
stages T1 – T3a. This to have a power of 80% in the detection of
a difference of 15% in the urinary incontinence rates between the groups;
but, at the end, 70 patients were evaluated and included in the study
due to ethical reasons. The interim analysis of the results showed a high
frequency of positive margins exclusively at the bladder neck level in
the bladder neck preservation group and the study was interrupted.
Surgery:
All patients were submitted to radical prostatectomy by the same surgeon
(MS), according to a technique previously published (14), preserving the
maximum of the distal sphincter complex. Drawing, during the surgery made
the decision of preserving or resecting the bladder neck. The bladder
neck preservation technique was described by Malizia et al. (7) and the
bladder neck resection technique was described by Walsh et al. (1).
Histopathological
study: All specimens were prepared and analyzed by the same pathologist
(KRL). The surgical specimens were fixed in 10% buffered formaldehyde,
for a period of four to sixteen hours. The whole gland was analyzed histologically
according to methods previously described (15). The whole gland was included
in the exam after its margins were stained with India ink.
For
the histologic study the specimens were treated as usual with dehydration
in alcohol and clarification in xylol, followed by inclusion in paraffin.
Cuts of 4 a 6 mm were stained with hematoxylin and eosin and analyzed
in a light microscope.
The
histopathological study of the surgical specimen included the assessment
of the Gleason score (16), tumor volume (17) and surgical margins. Margins
were considered positive when infiltrate tumor was found in the thin cuts
in the prostate apex and in the bladder neck as well as when the tumor
was interrupted at the borders stained with India ink.
Criteria
for evaluation: After the Foley catheter removal, on the fourteenth postoperative
day, the patients of both groups were evaluated as to urinary continence
in the following periods: 48 hours, two months and six months. Urinary
incontinence was defined as the need to use more than one pad per day.
Besides, immediate postoperative complications (up to the thirstiest postoperative
day) and delayed (between the first and the sixth postoperative months)
were recorded, including urinary fistulas and bladder neck strictures.
The same researcher (LJN) interviewed the patients, and he had no knowledge
about the type of procedure that the patient had had.
To
assess the surgery efficiency in what concerns the tumor removal, the
incidences of positive margins in both groups were compared, emphasizing
the study of the bladder neck.
The
neoplasm postoperative control was performed by dosage of specific prostate
antigen, total and prostate acid phosphatases in the serum and digital
rectal exam in the second month and at every six months after the first
dosage as well as yearly bone scan and chest radiography.
Statistical
analysis: To analyze the characteristics of both groups the Chi-square
test was used to compare age, stage, PSA and Gleason score. The Fisher
exact test was used to compare the results of continence at two and six
months, in the histopathological analysis and in the neoplasm biochemical
recurrence analysis. The Chi-square test was used to analyze the results
of continence in 48 hours. To reject the hypothesis of nullity the critical
level alpha = 5% (p = 0.05) was considered.
RESULTS
Patients
characteristics: The age of the patients ranged from 46 to 74 years (median
= 62.5), 68 were Caucasian and two, Asiatic. Thirty-five patients were
initially allocated to the bladder neck preservation group and the other
35 were submitted to bladder neck resection. In four of the 35 patients
of the preservation group it was not possible to spare the neck because
the median lobe was enlarged. These patients were included in the bladder
neck resection group, then with 39 patients. One patient died in the thirteenth
postoperative day due to a pulmonary embolism. The final groups had 38
patients in the bladder neck resection group and 31 in the bladder neck
preservation group. Both groups were comparable as to age, stage, PSA
and Gleason score (Table-1).
Urinary
continence: Among the 38 patients submitted to bladder neck resection,
eight (21%) reported urinary incontinence 48 hours after the Foley catheter
removal, 5 (13%) after two months and 2 (5%) after 6 months. Among the
patients who had the bladder neck spared, urinary incontinence was seen
in 31 patients (33%) after 48 hours, four (13%) after two months and one
(3%) after 6 months. As to urinary incontinence there was no statistically
significant difference between the two groups at any time.
Surgical
Margins: The pathological evaluation of the surgical specimens showed
positive margins at the bladder neck level in six of the 70 patients (8%),
with involvement by the neoplasm only in the bladder neck in three of
the 31 patients (10%) in whom these structures were spared. In none of
the patients submitted to bladder neck resection was bladder neck involvement
seen. Positive surgical margins were seen in other sites and bladder neck
in one patient of the preservation group and in two patients of the resection
group. Although there was a greater incidence of positive margins only
in the preservation group bladder neck, the figures showed no statistically
significant difference (p = 0.082).
Biochemical
recurrence: The specific prostate antigen dosage showed biochemical recurrence
of the neoplasm (> 0.3 ng/ml) in 6 (20%) of the 30 patients submitted
to bladder neck preservation and in 5 (15.15%) of the 33 submitted to
bladder neck resection (Table-2), after a median of 27 months of follow-up
(25 to 30 months). The difference between the 2 groups was not statistically
significant (p = 0.74). Adjuvant androgen suppressive therapy was introduced
for 3 of the 30 patients of the preservation group and for three of the
33 patients submitted to bladder neck resection because they showed a
high-risk histopathological study (Gleason > 8 or involvement of the
seminal vesicle by the neoplasm). Raised PSA was seen in all patients
with involvement of the surgical margin at the bladder neck level.
DISCUSSION
Although
in this study no urinary continence improvement was seen with the e bladder
neck preservation, other authors have shown that sparing the bladder neck
during radical prostatectomy, improves urinary continence in the postoperative.
Malizia et al. (7) reported 100% of early urinary continence and adequate
surgical margins in 20 patients submitted to radical prostatectomy with
bladder neck preservation. Shelfo et al. (8) studied retrospectively 365
patients submitted to the same technique, and have found 88% of urinary
continence. Even though they have found 32% of involved surgical margins,
they emphasized that the bladder was the only site involved in just 0.5%
of the cases. They concluded that the bladder neck sparing in prostatectomy
does not alter the chances of cure and improves the urinary continence
rates when compared to historical controls. In a prospective and sequential
study, Lowe (18) performed prostatectomy with bladder neck resection in
99 patients in the first year and, in the next year, 91 patients had the
bladder neck preserved. There was total continence after one month and
one year, respectively, in 11.2% and 86.3% in the resection group and
in 23.3% and 89.4% in the preservation group. According to him, the bladder
neck sparing could not be carried out in 15% of the planned cases due
to technical difficulties. He concluded that urinary continence returns
faster in the patients with bladder neck preservation but this difference
disappears nine months after the surgery. Gaker et al.(19) have seen more
favorable rates of early continence in the bladder neck preservation and
they state that this maneuver prevents the anastomotic strictures that
would compromise the continence.
On
the other hand, Licht et al. (20) evaluated, prospectively, 206 patients
submitted to radical prostatectomy with bladder neck preservation and
concluded that there is no improvement in urinary continence with the
preservation, yet this maneuver is associated to a smaller chance of the
vesico-urethral anastomosis stricture. They found 7% of positive margins
in the bladder neck and this fact is related to great volume tumors and
extra-prostate involvement.
Recently,
Kaye et al. (21) evaluated the bladder neck preservation technique associated
to three types of prostate apex dissection: “sphincter damaging”
(ligature and section of the dorsal vein complex); “sphincter repairing”
(the venous complex as part of the striated sphincter is incorporated
in the anastomoses); and “sphincter preserving” Myers technique
(22). The continence rates were of 90%, 93% and 97% and the average time
for its recovery was of 100, 52 and 30 days with the first, second and
third techniques, respectively, thus proving the importance of the external
sphincter preservation in the early return of continence.
In
this study all patients were operated preserving at most the integrity
of the distal sphincter complex. Continence was obtained 48 hours after
the Foley catheter removal in 67% of the patients with bladder neck preservation
and in 79% of the patients who had resection. After 2 months both groups
presented continence rates of 87%, without any statistical difference
between the 2 groups. This showed that the urinary continence after radical
prostatectomy depends on the distal sphincter mechanism.
During
this study an interim analysis showed involvement of the surgical margin
exclusively at the bladder neck level in 10% of the patients submitted
to this structure sparing and in none of the cases where the bladder neck
was resected. Epstein et al. (23) assessed the clinical impact of positive
surgical margin after prostatectomy. In 47% of the cases with positive
margins there was a progression of the disease while in the patients with
negative margins, progression was seen in 18% of the cases. This fact
led to the interruption of the study, as no greater continence rate was
seen with the bladder neck preservation and at the same time there was
a greater incidence of positive margins exclusively in the bladder neck
in this group. In a previous study, we compared bladder neck preservation
and resection in a randomized trial, looking at continence rates and surgical
cancer controls (24). It must be emphasized that in this previous study
(24), we found that a difference of positive surgical margins at the bladder
neck level did not reach statistical significance, but the value of “p”
was near to the significance level (p = 0.082). This number suggests that
the bladder neck preservation technique has a tendency to produce more
positive margins at the bladder neck level and this tendency might reach
a statistical significance if a greater number of patients were to be
studied in each group. Due to ethical reasons this hypothesis could not
be explored.
The
delayed postoperative analysis (27 months) of the experimental groups
showed that all the patients who had positive margins in the bladder neck
evolved with increase of PSA, proving that a positive surgical margin
is followed by high rates of neoplasm recurrence. On the other hand, it
was seen that the increase of PSA was the equivalent in both groups (p
= 0.74), probably due to other variables of the neoplasm that act as factors
of progression, besides the involvement of the bladder neck.
CONCLUSION
The bladder neck preservation in radical prostatectomies does not improve the postoperative continence rates, tends to produce more positive surgical margins at the bladder neck level, but the neoplasm evolution shows no difference when compared to patients submitted to bladder neck resection.
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______________________
Received: March 23, 2001
Accepted after revision: July 26, 2001
_______________________
Correspondence address:
Dr. Luciano Nesrallah
Rua Peixoto Gomide, 515 / 73
São Paulo, SP, 01409-001, Brazil
Fax: + + (55) (11) 3266-3695
E-mail: ljnesra@uol.com.br