© 2007 Foundation for Promotion of Cancer Research
Antegrade Radical Retropubic Prostatectomy with Preliminary Ligation of Vascular Pedicles in 614 Consecutive Patients
1 Department of Urology
2 Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
For reprints and all correspondence: Satoru Kawakami, Department of Urology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-Ku, Tokyo 113-8519, Japan. E-mail: s-kawakami{at}tmd.ac.jp
Received October 3, 2006; accepted February 24, 2007
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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Background: We present our procedure of antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles and assess the time trends of patient characteristics, surgical and oncological outcome in 614 consecutive patients in a single institution over a 12-year period.
Methods: From April 1994 to December 2005, 614 consecutive Japanese patients with cT1-3N0M0 prostate cancer underwent antegrade radical prostatectomy with preliminary ligation of vascular pedicles (dorsal vein complex and prostatic pedicles) prior to the tumor manipulation. Biochemical progression is defined as prostate-specific antigen value over 0.2 ng/ml or the initiation of therapy after surgery. Biochemical progression-free, cancer-specific and overall survival curves were calculated by the Kaplan–Meier method.
Results: During the study period pre-operative PSA, clinical T stage, duration of surgery, amount of estimated blood loss have decreased. Pathological stage showed a significant downward migration and the rate of positive surgical margin has also decreased. At a mean follow-up of 48 months, 21 men were dead including eight who died of prostate cancer. Overall and cancer-specific survival rates were 97/99% at 5 years and 89/95% at 10 years, respectively. Neoadjuvant hormonal treatment had no beneficial impact on oncological outcome of patients regardless of clinical stage. In 370 patients treated surgically alone, cancer-specific and biochemical progression-free survival rates were 99.6/80.5% at 5 years and 97.9/73.3% at 10 years for patients with clinical T1/2 disease and 95.5/41.9% at 5 years and 87.5/41.9% at 10 years for those with T3 disease, respectively. In the 370 patients biochemical progression-free survival has been significantly improved over the 12-year period (P < 0.0001).
Conclusions: Antegrade radical prostatectomy with preliminary ligation of vascular pedicles can be performed with excellent oncological outcome.
Key Words: prostate cancer • radical prostatectomy • survival • trends • PSA
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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The advent of anatomical retropubic radical prostatectomy by Walsh (1) has facilitated our understanding of surgical anatomy around the prostate and the majority of contemporary open radical prostatectomy is performed in a retrograde manner (2). It should be noted, however, that retrograde approach is not the sole way to remove the prostate. Nearly half century ago, Campbell proposed an antegrade approach in radical prostatectomy with a principle of preliminary ligation of the vascular pedicles (3). Recently, laparoscopic radical prostatectomy further provides surgeons detailed anatomical information by magnified view of the surgical field (4). Nowadays increasing number of radical prostatectomy is performed in a robot-assisted manner mostly with antegrade approach (5).
In the current study, we present a modified antegrade retropubic radical prostatectomy (aRRP) in which transection of the dorsal vein complex (DVC) and then of the lateral prostatic pedicles is performed prior to the manipulation of the tumor. We also assess the time trends of patient characteristics, surgical outcome and oncological outcome of the procedure in a single institution over a 12-year period.
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PATIENTS AND METHODS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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Patients
The study population was a consecutive 614 Japanese patients with clinically localized (cT1/2N0M0) or locally advanced (cT3N0M0) adenocarcinoma of the prostate treated with aRRP and limited pelvic lymph node dissection at our facility between April 1994 and December 2005. Indications for surgery included absence of clinically detectable metastatic lesion, absence of serious co-morbidity and more than 10 years of life expectancy. Clinical stage was assigned pre-operatively with the 2002 International Union Against Cancer TNM system (6). All patients underwent a digital rectal examination and transrectal ultrasonography. About a half of the patients after 1999 also received pre-operative MRI study. Impalpable and invisible cancer either on ultrasonography or MRI was classified as T1c, while palpable and/or visible cancers were subclassified, including T2a, T2b, T2c, T3a or T3b, with digital rectal examination and imaging results. The presence of metastasis was excluded with contrast-enhanced pelvic CT scans and radioisotope bone scans. Gleason score in the diagnostic biopsy specimen was assigned by one pathologist (YI). Of the 614, a total 244 patients (40%) received neoadjuvant treatment including combined androgen blockade in 214, LH–RH analog monotherapy in 16, antiandrogen monotherapy in 12 and diethylstilbestrol diphosphate in two patients.
Surgical Procedures
The aRRP was performed with preliminary ligation of vascular pedicles (the DVC and the lateral prostatic pedicles) based on the same concept of our previously reported procedure in radical cystectomy (7). After limited pelvic lymphnode dissection, the endopelvic fascia was incised and the proximal part of the DVC was suture ligated with 1-0 absorbable sutures. Following sutured ligation of the DVC distally, the DVC was transected sharply. The distal stump of the DVC was oversewn with 2-0 absorbable suture. After division of the prostatic base from the bladder neck, vasa deferentia were isolated and sectioned. Upward traction of the gland exposed the Denonvillier's fascia, which then could be incised sharply exposing the anterior surface of the rectum. Sharp and blunt dissection was used to develop the plane between the anterolateral surface of the rectum and the median aspect of the neurovascular bundles (NVBs). By pushing the rectum downwards and by pulling the prostate upwards, the NVBs were resected at their origin from the pelvic plexus. At this point the main vascular pedicles of the prostate were ligated before initiating the manipulation of malignant tissue. In the case of nerve-sparing surgery, the NVBs were detached from the seminal vesicles and then form the prostatic fascia. The decision to preserve one or both NVBs was based on the size, location, serum PSA level, cancer grade on biopsy and intra-operative findings. The dissection between the posterior aspect of the Denonvillier's fascia and the anterior rectal wall was extended until the apex of the prostate was reached. After sectioning the prostatic pedicles widely, the prostate remained attached only to the urethra and its surrounding structures. With the prostate maintained under posterior traction, anterior surface of the apex and the proximal part of the membranous urethra were exposed. The high mobility of the prostate allowed the urethra to be transected without damaging the urethral sphincter while minimizing the risk of leaving prostatic tissue in situ. After dividing the recto- urethral muscle, the prostate and the seminal vesicles were removed.
Every prostatectomy specimen was analyzed by one pathologist (YI). Pathological stage was assigned according to the TNM classification with one of four mutually exclusive groups: (1) pT0/2 N0, organ-confined, (2) pT3aN0, extracapsular extension, (3) pT3bN0, seminal vesicle invasion (SVI) and (4) pT0/3N1, lymphnode involvement (LNI).
Patients were followed with PSA tests and digital rectal examination every 3 months for one year, semiannually for 2–5 years and then annually afterward. Imaging studies including CT scans, MRI and radioisotope bone scan were indicated only after biochemical or clinical disease progression. In the current study we defined adjuvant therapy as therapy given prior to the confirmation of disease progression and salvage therapy as therapy given after confirmation of disease progression. Twenty patients received adjuvant including hormone therapy in 19 and external beam radiotherapy in one patient at their discretion. All these 20 patients had adverse pathological outcome including 15 patients with LNI, four with SVI and one with positive surgical margin. Biochemical progression is defined as PSA value over 0.2 ng/ml or the initiation of adjuvant therapy.
Data Analysis
To reveal the time trends of the patient characteristics, surgical outcome and oncological outcome, we divided the 12 years into three periods; 1994–97, 1998–2001 and 2002–05 during which 62, 177 and 376 patients underwent the surgery, respectively. Clinicopathological parameters were compared according to year of surgery. Analyzed clinical factors included patient age at operation (69 years or younger versus 70 years or older), PSA (0–10.0 ng/mL versus 10.1–20.0 versus 20.1–40.0 versus 40.1 or greater), clinical T stage (cT1/2 versus cT3), biopsy Gleason score (4–6 versus 7–10) and administration of neoadjuvant hormonal treatment (yes versus no); pathological factors included Gleason score on the prostatectomy specimen (4–6 versus 7–10), pathological stage (pT0/2N0 versus pT3aN0 versus pT3bN0 versus pT0-3N1) and surgical margin status (negative versus positive). Continuous variables were expressed as median (interquartile range) unless indicated otherwise. Association was evaluated on the basis of the Fisher's exact test for nominal variables and a one-way analysis of variance (ANOVA) for continuous variables. Overall, cancer-specific and biochemical progression-free survival curves were calculated with the Kaplan–Meier method and compared using the log-rank test. All calculated P values were two-sided and P < 0.05 was considered statistically significant. All analyses were performed using JMP version 6.0.0 (SAS Institute Inc, Cary, NC, USA).
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RESULTS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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The yearly number of patients who underwent aRRP increased from 10 in 1994 to 112 in 2005. Patient characteristics were compared according to year of surgery in Table 1. Although patient age at operation and the percentage of patients who received neoadjuvant hormonal treatment did not change during the study period (P = 0.38 and P = 0.24, respectively), pre-operative PSA and the proportion of patients with clinical T3 disease have been decreased significantly (P < 0.0001 and P = 0.015, respectively). The proportion of patients with a biopsy Gleason score less than 7 has also decreased (P = 0.032).
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Duration of operation, estimated blood loss and the frequency of requirement of allogeneous blood transfusion have decreased significantly (P < 0.0001) during the study period (Table 2). There was no peri-operative death. Significant downward migration of pathological stage was observed during the study period with increase in pathologically organ-confined disease (P < 0.0001) as well as with decrease in SVI (P < 0.0001) and LNI (P < 0.0001). Rate of positive surgical margin has fallen significantly (P < 0.0001). Gleason score on prostatectomy specimen, evaluable only in patients who did not receive neoadjuvant treatment (n = 370), did not change over the study period.
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In the current study cohort, 483 men (79%) and 131 men (21%) were diagnosed as having cT1/2 and cT3 disease, respectively. Whereas, the final pathological diagnosis revealed 379 (62%) and 235 men (38%) had pathologically organ-confined and non-organ-confined disease, respectively. Since significant downstaging by the neoadjuvant hormonal treatment has been demonstrated (8), we compared clinical and pathological stage in 370 men who did not receive neoadjuvant hormonal treatment. Discordance between clinical and pathological stage (either overstaging or understaging) was observed in 127 (34%) of the 370 patients. Discordance rate decreased significantly from 53% (21/40) in the 1994–97 period and 37% (42/114) in the 1998–2001 period down to 30% (64/216) in the 2002–05 period (P < 0.0001). Among the discordant cases, under-estimation by pre-operative staging was predominant throughout the 12 years of the study period.
The follow-up period ranged from 6 to 153 months (mean 48, median 39) with 204 patients (33%) followed longer than 5 years and 20 (3.3%) longer than 10 years. As of December 2006, a total of 18 of the 614 patients (2.9%) were lost to follow-up with the median period to the last contact of 6 months. Overall cancer-specific and biochemical progression-free survival curves for the entire cohort are shown in Fig. 1A. Eight patients (1.3%) died of prostate cancer during the study period, while 13 patients (2.1%) died of other causes. Thus, prostate cancer accounted for only 38% of all deaths. At 10 years after the surgery the actuarial probability of death from any cause was 10.9% and from prostate cancer 4.6% (Fig. 1). Of the 614 patients 474 (77%) remained continuously free of disease and 140 (23%) were assigned to treatment failure. Among the 140 patients, 20 patients (14%) including 15 patients with LNI and four with SVI received adjuvant therapy at their discretion before confirmation of biochemical or clinical progression while the remaining 120 patients (86%) had evidence of biochemical progression. Evidence of progression was apparent within 1 year post-operatively in 83 (59%) and within 2 years in 107 (76%) of the 140 patients, respectively. Only seven cases (5%) progressed after 5 years. The actuarial probabilities of remaining free of biochemical progression at 5 and 10 years for the entire cohort were 74 and 67%, respectively (Fig. 1).
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There was no difference in biochemical progression-free survival rate between 345 patients with cT1/2 cancer without neoadjuvant treatment and 138 patients with cT1/2 cancer who received neoadjuvant treatment (P = 0.78), or between 25 patients with cT3 cancer without neoadjuvant treatment and 106 patients with cT3 cancer who received neoadjuvant treatment (P = 0.32).
To reveal oncological effectiveness of the aRRP, overall, cancer-specific and biochemical progression-free survival curves for the 370 patients who did not receive neoadjuvant treatment prior to the aRRP are shown in Fig. 1B. Overall, cancer-specific and biochemical progression-free survival rates at 5 and 10 years were 97/94, 99/96 and 78/72%, respectively. In these 370 patients cancer-specific and biochemical progression-free survival curves were further compared according to the clinical T stage in Fig. 2. Biochemical progression-free survival rate of patients with cT1/2 disease (80% at 5 years and 73% at 10 years) was significantly better than that of patients with cT3 disease (42% at 5 years and 42% at 10 years) (P < 0.0001), while there was no difference in cancer-specific survival rates of these patients up to 10 years follow-up (P = 0.21).
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In the 370 patients treated with aRRP without neoadjuvant treatment, biochemical progression-free survival has been significantly improved over the 12-year period (P < 0.0001) as shown in Fig. 3.
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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The marked increase in the number of procedures over the study period is mainly due to the increasing prevalence of PSA screening in Japan and reflects the nation-wide trend in Japan (9,10). Marked decrease in initial PSA and in the proportion of patients with cT3 disease during the study period have resulted in a steady increase in the proportion of patients with favorable pathological outcome and an improved oncological outcome as defined by biochemical progression-free survival shown in Fig. 3. Along with the downward stage migration, decreasing frequency of positive surgical margin over the study period might also contribute to the improvement. Walsh's group reported a similar trend in 2370 patients treated with retrograde radical prostatectomy form 1982 to 1998 (11).
The marked decreases in the duration of operation and in the amount of estimated blood loss over the study period could be attributable to the accumulated experience and training in the procedure. A decreased frequency of requirement of an allogeneous blood transfusion was achieved by the routine use of pre-operative donation of autologous blood. We observed a steady improvement in pre-operative staging accuracy. As reported by several investigators (12), adopting MRI for pre-operative staging studies early in the study period might have contributed to this trend.
Our treatment policy is to administer neoadjuvant hormonal treatment for patients with clinically non-organ-confined disease but not for those with clinically organ-confined disease. Nevertheless, there has been no significant change in the proportion of patients who have undergone neoadjuvant hormonal treatment in the current cohort. This is due to the fact that a substantial proportion of the patients with clinically organ-confined disease were referred to our facility after the commitment of neoadjuvant hormonal treatment elsewhere. In the current Japanese cohort, we confirmed that neoadjuvant hormonal treatment has no impact on oncological outcome of either patients with cT1/2 cancers or those with cT3 cancers as reported previously (13,14).
Considering that the aRRP was indicated to patients with more than 10 years of life expectancy, the overall 10 year survival rate of 89% is an acceptable outcome. In patients without neoadjuvant hormonal treatment, we demonstrated that an excellent oncological outcome can be achieved by the aRRP with 5 and 10-year cancer-specific survival rate at 99.6/97.9% for cT1/2 disease, and 95.5/87.5% even for cT3 disease, respectively. The 5 and 10-year biochemical progression-free survival rates for cT1/2 disease and cT3 disease were 80.5/73.3% and 41.9/41.9%, respectively.
Focusing on the oncological outcome of patients treated by surgery alone, we compared the current results with those reported with retrograde radical prostatectomy. In the current study, aRRP achieved 5- and 10-year biochemical progression-free survival rates of 81 and 73% for clinically organ-confined disease, respectively (Fig. 2). In 5679 patients treated with retrograde radical prostatectomy at the Mayo Clinic, Ward et al. reported 5- and 10-year biochemical progression-free survival rates of 76 and 63%, respectively, using a cut-off PSA value for biochemical progression at 0.4 ng/ml (15). In 3478 consecutive patients treated with retrograde radical prostatectomy, Catalona's group reported that 10-year biochemical progression-free survival rates for the entire cohort, cT1c, cT2a, cT2b/c were 68, 77, 69 and 59%, respectively (16). Walsh's group reported 5-, 10- and 15-year biochemical progression-free survival rates for 2370 patients treated with retrograde radical prostatectomy of 84, 74 and 65%, respectively, using a cut-off PSA value for biochemical progression at 0.2 ng/ml (11). Although comparisons must be made with caution because of differences in population and criteria for biochemical progression, oncological outcome of the aRRP can be more than comparable with those of retrograde RRP.
Our results indicated the feasibility of the aRRP procedure in regard to surgical and oncological outcomes. From the current results, the following advantages of the aRRP can be postulated. First, it can minimize the risk of apical fracture by apical dissection being performed after the full mobilization of the prostate. This notion is supported by a recent report by Serni et al. that a low incidence of positive surgical margins in high risk prostate cancer treated with a modified antegrade RRP (17). Second, it might reduce the risk of intra-operative cancer dissemination by preliminary ligation of vascular pedicles before manipulating the cancer-bearing organ.
Several limitations should be admitted in our current study. Because currently only a small fraction of patients have died of disease in our study cohort, it would require 5–10 more years to determine predictors of cancer-specific survival. Stage-specific analyses of detailed oncological outcome and risk factor for biochemical progression are now under investigation.
In conclusion, antegrade RRP with preliminary ligation of vascular pedicles can be performed with excellent oncological outcome.
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Conflict of interest statement |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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None declared.
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References |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONConflict of interest statementReferences |
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