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- PATIENTS AND METHODS
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At present there are several definitive surgical options for managing clinically localized prostate cancer, including radical retropubic prostatectomy (RRP), laparoscopic RP (LRP), and robot-assisted RP (RARP) [1–12]. Given the novelty and interest in minimally invasive/minimal access options, studies comparing the laparoscopic approaches to RRP have been published [5,7,12–14]. Collectively, these reports have improved our understanding of perioperative morbidity and quality-of-life (QoL) differences among treatment approaches. The comparative studies have also addressed early differences in oncological outcomes, yet a potential concern is the inclusion of patients with varying clinical characteristics into such treatment groups [5,7,12]. This method might bias the accuracy of oncological outcomes, not only for the laparoscopic approach but also for RRP. While a long-term follow-up will ultimately be required to determine the oncological efficacy and safety, differences in early oncological results and perioperative complications are equally important for patient counselling.
In the present medical environment patients are intimately involved in their surgical treatment decision-making and many present to the urologist with a pre-formed treatment plan. For this reason randomized clinical controlled trials comparing RARP to RRP are not logistically feasible and we must therefore rely on case-control matched comparisons. When comparing prostate cancer outcomes it is important to compare within the treatment era (i.e. before or after the PSA era). The goal of the present retrospective study was to determine the perioperative complications and early oncological results among patients treated with RARP or RRP in the same treatment period after the advent of PSA testing, thus eliminating the bias of stage and grade migration. Analysis of the outcome was facilitated by matching patients treated with RRP in a 2:1 ratio with those who had RARP, on the basis of age, preoperative serum PSA level, clinical stage, and biopsy Gleason grade.
PATIENTS AND METHODS
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- PATIENTS AND METHODS
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After approval from the Mayo Clinic Institutional Review Board, we identified the initial consecutive series of 294 patients undergoing RARP at our institution for clinically localized prostate cancer, between August 2002 and December 2005, using the Mayo Clinic Prostatectomy Registry. Our RP registry prospectively records patient data before during and after RP. A registered nurse from the Registry monitors the outcomes of all patients annually, including those who were followed up elsewhere. The nurse abstractor contacts patients who receive care elsewhere by correspondence with the patient or their primary-care physician and/or urologist. The type of surgical approach for individuals in the registry is determined by the patient. Using the same registry, a comparison the RRP group (588 men) from the same era after PSA was matched 2:1 with the RARP group for year of surgery, age, preoperative serum PSA level, clinical stage and biopsy Gleason grade. Clinical stage was determined by a DRE. All patients with a preoperative PSA level of ≥10 ng/mL or Gleason grade of >7 also had CT of the abdomen and pelvis, and total-body bone 99mTc-scintigraphy to evaluate any metastatic disease.
RARP was performed by three surgeons and RRP by 17, using modified variations of previously reported techniques [4,8]. Most RARP procedures were done by one surgeon (M.T.G.) and the RRP group included residents in training, thus the effect of initial experience was present in both cohorts. All patients had a pelvic lymphadenectomy. The operative duration was measured from time of anaesthesia induction to laryngeal extubation, and included docking of the robotic system (da Vinci Surgical, Sunnyvale, CA, USA) but not the set-up. All specimens had an immediate pathological evaluation, with a limited sampling technique using frozen sections with subsequent examination of paraffin-embedded sections the following day. All surgical margins, including the prostate base, apex, urethra, bladder neck, capsule, periprostatic soft tissues, and seminal vesicles were evaluated. All clinical and pathological data were entered prospectively into the registry during the above period. Stage and grade were assigned using the 1997 TNM system and the Gleason scheme, respectively [15,16]; the primary Gleason pattern was defined as the predominant portion in more than half of the specimen.
Immediate perioperative complications were defined as those occurring within a month of surgery; late complications were those occurring at >1 month after surgery. Follow-up visits after surgery, unless related to a perioperative complication, were typically at 3-month intervals for a year, then semi-annually for a year, and then yearly thereafter. The examinations included an assessment of serum PSA level and a DRE. When clinically indicated after surgery, other diagnostic testing was used, including CT, MRI, chest radiography, and/or bone scans.
All patients were requested to complete a non-validated standardized QoL questionnaire devised by our department at 1 year after surgery. If the patient had no urinary leakage or required only a security pad, this was defined as being continent. Potency was defined as erections satisfactory for intercourse with or without the use of phosphodiesterase-5 (PDE-5) inhibitors. Biochemical progression (i.e. PSA progression) was defined as one serum PSA level of >0.4 ng/mL. Clinical local recurrence was the development of a palpable nodule on a DRE, or pelvic lesion identified on MRI in conjunction with a detectable serum PSA level. Systemic progression was defined as a visualized abnormality on imaging that was convincing for metastatic disease. Death from prostate cancer was defined as death from metastatic prostate adenocarcinoma.
The RARP and RRP groups were compared using the rank-sum test (continuous or ordinal factors) and chi-square or Fisher’s exact test (nominal factors). Biochemical progression-free survival (PFS) was estimated using the Kaplan-Meier method, and in all tests P < 0.05 was taken to indicate significance.
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The clinical characteristics and year of surgery (matching factors) are shown for patients treated in the comparative study (Table 1). Data on pathological stage, pathological Gleason grade, DNA, margin positivity, the location of positive margins, and treatment characteristics for all patients are also shown in Table 1. While overall differences in margin positivity were not significant among treatment approaches, apical positive margins were more common with the RRP technique (4.4% vs 9.5%, P = 0.008). The total hospital stay was significantly shorter in the RARP group (P = 0.004).
Table 1. The clinical characteristics of 294 patients who had RARP and 588 who had RRP, and the pathological and treatment characteristics, assessed in the matched comparison analysis
|No. of patients||294||588|| |
|Year of surgery, n (%)|| || || |
| 2002|| 2 (0.7)|| 12 (2.0)|| |
| 2003|| 51 (17.3)||112 (19.0)|| |
| 2004||112 (38.1)||223 (37.9)|| |
| 2005||129 (43.9)||241 (41.0)|| |
|Median (range):|| || || |
| age at surgery, years|| 61.0 (38.0–76.0)|| 61.0 (41.0–77.0)|| |
| pre-op PSA level, µg/mL|| 4.9 (0.5–33.5)|| 5.0 (0.6–39.7)|| |
|Clinical TNM stage, n (%)|| || || |
| T1a or T1b|| 0|| 4 (0.7)|| |
| T1c||214 (72.8)||418 (71.1)|| |
| T2a|| 75 (25.5)||130 (22.1)|| |
| T2b|| 4 (1.4)|| 28 (4.8)|| |
| T3 or T4|| 1 (0.3)|| 8 (1.4)|| |
|Biopsy Gleason grade, n (%)|| || || |
| <6|| 2 (0.7)|| 0|| |
| 6||212 (72.1)||441 (75.0)|| |
| 7|| 70 (23.8)||133 (22.6)|| |
| ≥8|| 10 (3.4)|| 14 (2.3)|| |
|No. of patients||293||588|| |
|Pathological TNM stage|| || ||0.343|
| T2aN0||105 (35.8)||206 (35.0)|| |
| T2bN0||159 (54.3)||315 (53.6)|| |
| T3aN0|| 15 (5.1)|| 35 (6.0)|| |
| T3b4 N0|| 14 (4.8)|| 24 (4.1)|| |
| TxN+|| 0|| 8 (1.4)|| |
|Pathological Gleason grade|| || ||0.792|
| 6||192 (65.5)||391 (66.5)|| |
| 7|| 87 (29.7)||167 (28.4)|| |
| ≥8|| 14 (4.8)|| 30 (5.1)|| |
|Positive surgical margin|| 46 (15.6)||100 (17.0)||0.608|
| apex|| 13 (4.4)|| 56 (9.5)||0.008|
| base|| 4 (1.4)|| 10 (1.7)||1.000|
| urethra|| 5 (1.7)|| 4 (0.7)||0.168|
| anterior|| 1 (0.3)|| 5 (0.9)||0.670|
| posterior|| 27 (9.2)|| 49 (8.3)||0.703|
|Nerve-sparing procedure|| || ||0.017|
| no|| 53 (9.0)|| 53 (18.0)|| |
| full||509 (86.6)||221 (75.1)|| |
| partial|| 26 (4.4)|| 20 (6.8)|| |
|Days in hospital|| || || 0.004|
| 1|| 86 (29.3)||114 (19.4)|| |
| 2||176 (59.9)||400 (68.0)|| |
| 3–6|| 31 (10.5)|| 65 (11.0)|| |
| ≥7|| 1 (0.3)|| 9 (1.6)|| |
|Adjuvant hormones†|| 2 (0.7)|| 39 (6.6)||<0.001|
|Adjuvant radiation†|| 3 (1.0)|| 6 (1.0)|| 1.000|
There was a significant difference in median operative duration between the RARP and RRP groups (236 vs 204 min; P < 0.001). By the last 100 RARP cases there was no significant difference in median operative duration between the groups (211 vs 228 min; P = 0.14). Table 2 shows the operative duration and highlights the effect of experience for RARP compared to RRP.
Table 2. Comparison of operative times (induction of anaesthesia to extubation) of the RARP and RRP groups
|Period||Median (25–75th percentile) duration, min||P|
|All||294||236 (204–285)||588||204 (162–268)||<0.001|
|Early|| 94||295 (248–357)||188||190 (158–245)||<0.001|
|Middle||100||235 (201–268)||200||206 (162–268)||0.004|
|Late||100||211 (186–236)||200||228 (169–288)||0.140|
The incidence of perioperative complications (Table 3) was not significantly different between the RARP and RRP groups (8.0% vs 4.8%, P = 0.064). Of the early complications, incisional hernia was more common in the RARP group (1.0% vs none, P = 0.038). The need for peri-or intraoperative blood transfusion was significantly higher in the RRP group, at 13.1% (77) than in the RARP group, at 5.1% (15; P < 0.001). Conversely, early wound complications (not confirmed by culture) were more common in the RRP group (0.7% vs 3.7%, P = 0.010). Extravasation of contrast medium at cystography was more common in the RARP group (9.1% vs 2.5%, P < 0.001). Late complications are also listed in Table 3; there were significantly fewer bladder neck contractures in the RARP than in the RRP group (1.2% vs 4.6%, P= 0.018). At the 1-year follow-up there was no significant difference in continence (RARP 91.8%, RRP 93.7%, P = 0.344) or potency (RARP 70.0%, RRP 62.8%, P = 0.081) rates between the groups.
Table 3. Early perioperative and late complications associated with RARP and RRP, based on patients treated in the matched comparison study
|Early|| || || |
|No. with early (1-month) follow-up||286||564|| |
|Any||23 (8)||27 (4.8)||0.064|
| Bladder neck contracture||0 (0)||1 (0.2)||0.476|
| Haemorrhage/haematoma||10 (3.5)||10 (1.8)||0.150|
| Hernia||3 (1)||0 (0)||0.038|
| Renal failure||0 (0)||1 (0.2)||0.476|
| Sepsis||0 (0)||1 (0.2)||0.476|
| Stricture||2 (0.7)||3 (0.5)||0.763|
| Ureteric obstruction||0 (0)||1 (0.2)||0.476|
| Urinary retention*||8 (2.8)||7 (1.2)||0.104|
| UTI||3 (1)||6 (1.1)||0.984|
|Other|| || || |
| Deep vein thrombosis||1 (0.3)||7 (1.2)||0.203|
| Drug reaction||2 (0.7)||7 (1.2)||0.466|
| Ileus||5 (1.7)|| 10 (1.8)||0.982|
| Lymphocele||2 (0.7)||4 (0.7)||0.987|
| Lymphoedema||0 (0)||1 (0.2)||0.476|
| Myocardial infarction||0||0|| |
| Pulmonary embolism||1 (0.3)||4 (0.7)||0.517|
| Respiratory failure||2 (0.7)||3 (0.5)||0.763|
| Requiring transfusion||15 (5.1)||77 (13.1)||<0.001|
| Stroke||3 (1)||3 (0.5)||0.395|
|Late|| || || |
|No. with 1-year follow-up||248||492|| |
| Abdominal abscess||0 (0)||2 (0.4)||0.554|
| Bladder neck contracture||3 (1.2)||23 (4.6)||0.018|
| Deep vein thrombosis||1 (0.4)||6 (1.2)||0.434|
| Hernia||10 (4.0)||14 (2.8)||0.387|
| Lymphocele||1 (0.4)||5 (1.0)||0.670|
| Lymphoedema||0||0|| |
| Pulmonary embolism||0 (0.0)||5 (1.0)||0.175|
| Urethral stricture||8 (3.2)||6 (1.2)||0.083|
|Continence at 1 year†|| || ||0.344|
| N||252||496|| |
| With continence||224 (91.8)||446 (93.7)|| |
| No pads||199 (81.6)||419 (88.0)|| |
| Security pad only||25 (10.3)||27 (5.7)|| |
| Without continence||20 (8.2)||30 (6.3)|| |
| 1–2 pads/day||17 (7.0)||23 (4.8)|| |
| 3 pads/day||3 (1.2)||7 (1.5)|| |
| Previous incontinence||1||6|| |
| Unknown||7||14|| |
|Potency at 1 year‡|| || ||0.081|
| Impotent||61 (30)||155 (37.2)|| |
| Potent||142 (70)||262 (62.8)|| |
| Impotent previously||32||49|| |
| Unknown||17||31|| |
The median follow-up was 1.3 years, with disease progression events for both groups listed in Table 4. During the follow-up there were no deaths related to prostate cancer. The 3-year biochemical PFS was not significantly different between the groups (RARP 92.4%, RRP 92.2%; P = 0.69, Fig. 1).
Table 4. Clinical local recurrence, biochemical progression, and death from disease for patients treated with RARP and RRP for localized prostate cancer. The mean (sem) 3-year Kaplan-Meier PFS (% free of PSA progression) was 92.4 (2.3)% for RARP and 92.2 (1.8)% for RRP
|Variable||RARP, n||RRP, n|
|Clinical local recurrence||3||5|
|Death from prostate cancer||0||0|
|Death from any cause||4||4|
|Median (25–75 percentile)|
|follow-up, years||1.3 (1.2–2.2)||1.3 (1.2–2.4)|
- Top of page
- PATIENTS AND METHODS
- CONFLICT OF INTEREST
In the present study, patients were matched 2:1 to RRP or RARP for age, preoperative serum PSA level, surgical period, clinical stage and biopsy Gleason grade. Using this design, we found at that the early follow-up oncological outcomes, specifically the overall positive surgical margin rates, were not significantly different between the RARP- and RRP-treated patients. Furthermore, there was no significant difference in risk of disease progression between RARP and RRP. Overall early perioperative complications were not significantly different between the groups, but there was a higher rate of wound hernias in the RARP group. Although wound herniation might be a result of surgical technique, these differences could also be related to the accumulating experience for the RARP procedure, which has been estimated to be 10–20 cases [15,17]. While the late development of bladder neck contracture was more common after RRP there was no difference in continence between the groups at 1 year after surgery. Also, there was no difference in self-reported potency rates between the RARP and RRP groups at the 1-year follow-up.
Interest in limited-access RP techniques has increased, amplifying the need for the accurate reporting of associated perioperative complications and early oncological outcomes. Patients seeking treatment for adenocarcinoma of the prostate are extensively counselled about the many treatment options available, and often have conducted extensive independent research on this subject. They not only present seeking a specific treatment, but often a specific surgeon. For these reasons randomized clinical controlled trials comparing RRP to RARP would be difficult, if not impossible. We are therefore limited to retrospective comparative evaluations. Studies with level II evidence comparing RRP and RARP are impossible if patients are in treatment cohorts with variable clinical and pathological characteristics. At some institutions RRP is being abandoned or relegated to only those patients with the most unfavourable clinical features. This trend, from a standpoint of accurate reporting, hinders the development of comparative studies between RRP and laparoscopic alternatives. Also, data from any modern RP series (open, laparoscopic, robotic) cannot be compared to historical RRP controls, given the favourable stage migration witnessed in the era of PSA screening and the impact on disease progression [18,19]. Furthermore, with the mounting interest in laparoscopic techniques, the opportunity to conduct comparative studies for prostate cancer treatments is dwindling. At our institution, we remain strongly rooted in RRP, based on long-term oncological results, but have also embraced RARP. The volume of surgery and the involvement of many surgeons at our centre allow an analysis of matched pairs, a technique invaluable for comparing outcomes of RARP to RRP.
Although QoL is a significant consideration, oncological control is the paramount goal of RP. Interestingly, despite a recognized effect of experience in the RARP group. oncological outcomes were similar to those in the RRP group. In the present study margin positivity rates were equivalent between RARP and RRP (15.6% vs 17.0%) and are comparable to results reported previously for RARP [5,7,11,12]. However, in a subset analysis the apical positive margin rate was higher in the RRP than the RARP group (9.5% vs 4.4%). Various factors influence margin positivity, including surgical technique and specimen handling. In many cases we believe that margin positivity reflects tumour biology more than technique, and that this factor is a poor surrogate for cancer control. Some have also used new specimen-handling strategies that might influence the results of RARP. Menon et al. reported taking an apical biopsy with an immediate pathology review to assess the apical margin status, so that further resection could be done if necessary. Visualization might account for our lower apical margin rate in the RARP group in the subset analysis. However, with the introduction of ×4.3 optical loupes, visualization at the time of RRP might approach that of RARP and decrease the rate of positive apical margins. Magera et al. reported a 75% decrease in the risk of apical positive margins when ×4.3 optical loupe magnification is used compared to ×2.5. In the present study, the use of ×4.3 optical loupes was limited to only one surgeon in the RRP group and therefore could account for the difference in apical margin rates between the RARP and RRP groups.
Despite a higher percentage of RRP patients receiving hormone deprivation therapy within 90 days of their surgical procedure, early PSA and clinical progression data for RARP and RRP patients in the present study were not significantly different. We recognize that because of the nature of prostate cancer recurrence, a longer follow-up is still required. These observations have also been identified by other investigators in unmatched comparisons [5,7,12].
The transfusion rates were higher for RRP than RARP; at our institution, blood transfusions are not given on the basis of a standardized protocol. Indeed, the practice patterns of some surgeons can vary widely, as well as the absolute indications for a blood transfusion. For example, some surgeons use predetermined haemoglobin levels alone to determine the need for blood transfusion. Other surgeons transfuse patients when they are symptomatic. In essence, a comparison of these surgeons would be biased largely by practice patterns. Therefore, the difference in transfusion rates between RRP and RARP in the present study does not solely reflect surgical technique.
Length of hospital stay was another variable measured in the present study; patients in the RARP group had a significantly shorter hospital stay than those in the RRP group. These results might indicate that the discharge time is less after RARP than RRP, but the length of hospitalization might also reflect individual surgeons’ practice patterns. A recent study showed that the length of hospitalization can be similar between RRP and RARP patients when using defined patient-treatment pathways. Of further interest, the length of hospital stay did not predict readmission rates .
In the present study extravasation at cystography was more common after RARP. This is an interesting result, because RARP is thought to increase the precision of the anastomosis. This result probably represents the accumulation of experience for making a running anastomosis compared with an interrupted anastomosis used for RRP. In addition, the protocol for taking a cystogram is not standardized at our institution. While most RARP patients had a cystogram, not all RRP patients had cystography, so the true rate of extravasation after RRP is unknown. We also identified more postoperative wound complications after RRP than RARP. These were not culture-confirmed complications and therefore seromas cannot be separated from true wound infections. For this reason we think that wound infection rates cannot be reported reliably.
There were some limitations to the present study. First, the study was retrospective but used a RP database of prospectively followed patients. Second, the statistical power must always be considered in negative studies. With a presumed baseline rate of complications of 1%, the present study had 80% power to detect a 3.2% point increase to 4.2%. Thus, if the baseline rate of complications was ≤1% then the study might not have enough patients to detect small differences between the treatments. Third, the QoL questionnaire completed by patients has not been validated and was devised by our department . Nonetheless, the criteria used for both study cohorts were equivalent and differences in QoL outcomes were comparable.
In conclusion, there were no significant differences in overall complications between the RARP and RRP groups. Wound hernias were more common after RARP and the late development of bladder neck contractures were more common after RRP. However, at the 1-year follow-up there was no difference in self-reported continence or potency rates between the groups. Oncological efficacy in terms of margin positivity was not significantly different between the groups. Likewise, at the early follow-up, differences in biochemical PFS among patients in this matched comparison were not significant.