4Clinical effectiveness of robotic compared with laparoscopic techniques

Publication Details

Quantity and quality of evidence

Number of studies identified

The searches identified 2722 potentially relevant titles and abstracts (Figure 6), from which 914 reports were selected for full-text eligibility screening. Of these, 58 reports (54 studies) were included and 856 reports were excluded with reasons for exclusion detailed in Figure 6. We attempted to obtain further details for 69 of the 80 (86%) reports that were excluded because of lack of clear information on the number of patients for each baseline clinical stage and which had contact details available. Nineteen replies were obtained. Only one of these 19 reports89 was subsequently deemed eligible for inclusion, but confirmation of this was received too late for it to be included in the review. Appendices 5 and 6 give the bibliographic details of the included and excluded studies respectively.

FIGURE 6. Flow chart of the number of potentially relevant reports of identified studies and the numbers subsequently included and excluded from the clinical effectiveness review.

FIGURE 6

Flow chart of the number of potentially relevant reports of identified studies and the numbers subsequently included and excluded from the clinical effectiveness review.

Number and type of included studies

The searches identified one RCT of laparoscopic versus open radical prostatectomy90 and 57 non-randomised comparative reports of 53 studies from 40 different clinical institutions: eight robotic versus laparoscopic prostatectomy;9198 four robotic versus laparoscopic versus open prostatectomy [three primary,99101 one secondary102 (earlier report of the same study but containing unique data)]; 18 robotic versus open prostatectomy (16 primary,103118 two secondary119,120) and 27 laparoscopic versus open prostatectomy (26 primary,121146 and one secondary147). There were three conference abstracts: two comparing robotic versus laparoscopic prostatectomy94,97 and one comparing robotic versus laparoscopic versus open prostatectomy.102

Four studies were considered to include potential patient overlap: the study conducted by Menon and colleagues95 was a comparison of 40 laparoscopic and 40 robotic prostatectomies performed between 23 October 2000 and 22 October 2001; Tewari and colleagues116 report an extension of this work but compared 100 open and 200 robot operations between October 1999 and December 2002. As these studies included different comparators, they were treated as separate studies but the potential for overlap of robotic prostatectomy patients was noted. Similarly, Joseph and colleagues94 report a comparison including 800 laparoscopic cases from the Henri Mondor hospital, France, and 745 robotic cases from the University of Rochester, USA, between 2002 and 2006. An earlier publication93 analysed the last 50 cases from a series of 70 laparoscopic and 200 robotic cases from the University of Rochester (dates not given). The studies were treated as separate. Similar affiliated institution details of first authors were noted for seven studies: those by Anastasiadis122 and Salomon,140 Ficarra106 and Fracalanza,107 and Greco,129 Jurczok131 and Fornara.127 These studies report overlapping treatment dates and similar procedures but it is unclear whether or not they include patient overlap as details of the institutions where the men were treated are not clearly given within the reported text. Similarly, we noted similar author institution details for another seven studies: those by Malcolm,110 Ball99 and Soderdahl,142 Trabulsi98 and Brown,125 and Loeb109 and Wagner146 although these involved different comparison groups and were treated as separate studies.

The 57 non-randomised comparative reports (of 53 studies) included 28 prospective and 17 retrospective reports. Three studies92,112,114 included a mixture of prospective and retrospective data and eight96,97,100,119,123,132,134,138 did not report the method of data collection. The method of data collection was uncertain in the study by Kim and colleagues132 because of a limited translation of the full-text version. Table 4 provides further details of the number and type of included studies.

TABLE 4. Number and type of included studies.

TABLE 4

Number and type of included studies.

The RCT conducted by Guazzoni and colleagues90 comparing laparoscopic with open prostatectomy was set in Italy. Half of the included non-randomised studies were conducted in the USA (28/57, 49%). The remaining studies were conducted in France,91,9496,101,122,140 Italy,106,107,114,123,129,134 Germany,127,131,137 Japan,135,136,144 Canada;121,130 there was one study from each of Australia,105 Austria,139 Brazil,141 Chile,133 Croatia,143 Republic of Korea,132 Spain,138 Sweden104 and Taiwan, Province of China.113 Of the non-randomised comparative studies comparing robotic with laparoscopic radical prostatectomy, three primary full-text studies92,93,98 and one conference abstract97 were set in the USA, one conference abstract was set in both the USA and France94 and three studies were set in France.91,95,96 Of the non-randomised comparative studies comparing robotic, laparoscopic and open radical prostatectomy, two primary studies99,100 and one secondary report102 were set in the USA and one study was set in France.101 Of the non-randomised comparative studies comparing robotic and open radical prostatectomy, 10 primary studies103,108112,115118 and two secondary reports119,120 were set in the USA, one study was set in Australia,105 three primary studies106,107,114 were set in Italy, one study was set in Sweden104 and one was set in Taiwan, Province of China.113 Of the non-randomised comparative studies comparing laparoscopic and open radical prostatectomy, seven primary studies124126,128,142,145,146 and one secondary report147 were set in the USA, three primary studies127,131,137 were set in Germany, three primary studies135,136,144 were set in Japan, three primary studies123,129,134 were set in Italy, two primary studies122,140 were set in France and one study each was set in Austria,139 Brazil,141 Canada,121 Chile,133 Croatia,143 Republic of Korea132 and Spain.138

The four full-text publications that required translation paired with their original language were Fornara and Zacharias127 (German), Kim132 (Korean), Soric143 (Croatian) and Raventos Busquets and colleagues138 (Spanish).

Characteristics of patients

The 58 reports included 21,126 men at enrolment. Excluding secondary reports and following exclusions because of ineligibility or participant dropout, the final study analyses included 19,064 men, of whom 6768 underwent robotic radical prostatectomy, 4952 underwent laparoscopic radical prostatectomy and 7344 underwent open radical prostatectomy. The demographic and disease characteristics of these included men are summarised in Table 5.

TABLE 5. Summary description of the individual patient characteristics for the included studies, where data were combinable, from the information reported by the study authors.

TABLE 5

Summary description of the individual patient characteristics for the included studies, where data were combinable, from the information reported by the study authors.

All studies reported age with a median (interquartile range) of 62 (60–64) years and a total range of 35–84 years.

Baseline clinical tumour staging data were reported for all studies except that conducted by Bolenz and colleagues;100 however, clinical staging data for this study were available from an earlier report in abstract form.102 Eight reports107,111,120,126,139,141,143,147 did not report specific baseline clinical stage, simply reporting their inclusion criterion as ‘≤ cT1–T2’, and one109 did not report clinical stage by procedure. The baseline clinical tumour staging was similar between the laparoscopic and robotic radical prostatectomy patients with 68% and 69%, respectively, categorised as T1.

Less than half of the included reports (23/58, 40%)91,98,99,101,103,105108,110,115,117121,125,128,135,136,142,145,146 gave detailed biopsy Gleason scores for men undergoing prostatectomy in the format we required: numbers of men categorised as Gleason score ≤ 6, 7 or ≥ 8. Seven studies90,95,97,111,126,139,141 and one secondary report147 did not report biopsy Gleason grades or score. Over one-third of the included reports (21/58, 36%) reported either mean9395,113,122124,129,130,132,139,140,143,144 or median104,114,127,131,133,134,137 scores. The remaining reports presented details using different scoring formats90,92,102,138,141 or did not present separately by procedure.100 Two-thirds of men undergoing both laparoscopic and robotic radical prostatectomy had a Gleason score ≤ 6.

Fifty reports90,91,93101,103109,112119,122125,127146 gave preoperative PSA values, with the majority (38/50, 76%) reporting mean PSA for each group of men. Nine studies106108,131,134,141,142,144,145 reported median group PSA values, whereas two studies135,136 reported mean and median PSA and one study119 reported PSA range only. Combining the median and mean PSA values across all of the studies demonstrated slightly lower levels of preoperative PSA in the robotic than in the laparoscopic procedures: 6.3 ng/ml and 7.2 ng/ml respectively. Three studies92,121,126 reported the number of men in each group falling into varying ranges of PSA values but as the ranges were inconsistent we were unable to include these data in the summary.

The postoperative Gleason sum score following pathological examination of the prostate was similar between the robotic and laparoscopic patients with 50% of the men in both groups with combinable Gleason information having a Gleason score ≤ 6. Pathological staging assigned following consideration of the operative finding during surgery and pathological examination of the removed prostate was similar between the robotic and laparoscopic patients with 78% of the men with combinable staging information in both groups categorised as pT2. There was a trend towards worse disease characteristics in men undergoing open prostatectomy with 55% having a post-prostatectomy Gleason score > 6 and 30% categorised as pT2 or higher.

Twenty-nine primary reports9093,96,99,100,106,108,110113,118,122,123,125,126,128,129,132,135137,139,142,144146 and two secondary reports102,119 reported the use of nerve-sparing techniques.

Overview of types of outcomes reported

The numbers and types of included studies reporting our main considered outcomes are summarised below.

Efficacy

Thirty-nine studies (67%)90,9498,101,103,105109,112116,118,122,123,125127,129134,137141,143146 reported data on the rate of positive surgical margins in the excised prostate specimen.

Thirteen studies (22%)95,101,103,108,109,112,113,115,116,123,133,137,140 reported the rate of biochemical recurrence, but the time points at which this was censored, the definition of biochemical recurrence and the threshold values of PSA used varied between studies.

The need for and outcome of further treatment for prostate cancer recurrence was reported by one study. Dahl and colleagues126 reported information on the numbers of men requiring further cancer treatment consisting of salvage external beam radiation therapy, androgen deprivation therapy or both for cohorts of men undergoing laparoscopic or open prostatectomy.

Eight studies90,111,116,130,135137,139 reported quality-of-life data using validated measures.

Safety

The majority of reports (45/58, 78%) included data on perioperative adverse events.

Thirteen primary reports93,94,99,103,109,110,130,135,136,141,142,144,145 and one secondary report147 did not report perioperative safety outcomes.

Four studies104,105,126,140 reported deaths within 30 days postoperatively because of surgical complications.

Postoperative incontinence and sexual dysfunction

Twenty-one studies (36%)91,93,97,99,106,108,110,113,114,116,123,126,128130,133,135137,142,146 provided data on urinary incontinence postoperatively. Three other studies112,122,139 reported continence data in a form that could not be converted to the numbers of incontinent men, which was our required format for meta-analysis. Two studies also reported data that we were unable to use because of presentation in graph format rather than numbers of incontinent men105 or because of presentation of immature data.95 The study conducted by Carlsson and colleagues104 reported the number of patients requiring additional surgery for urinary incontinence between 30 days and 15 months after radical prostatectomy.

Nineteen studies (33%)93,99,106,108,110,112114,116,122,123,126,128,129,133,135,136,142,146 provided data on sexual function following prostatectomy.

Risk of bias

Overall assessment of risk of bias

Forty-eight reports from 28 individual author-affiliated institutes were assessed for risk of bias. The secondary reports by Dahl and colleagues147 and Chan and colleagues119 contained unique outcomes not included in the associated primary studies103,126 and we therefore conducted risk of bias assessment for both reports. Twenty-four reports (50%)92,93,95,96,98,104108,112,113,115,116,124,126,130,134,136,139,142,144,146,147 were judged to be at high overall risk of bias, 13 (27%)90,99101,103,117,118,122,128,129,137,141,145 were low risk and 11 (23%)109,111,114,119,121,123,125,131,135,140 were judged unclear. Analysis of inter-rater agreement for overall assessment of risk of bias gave a kappa = 0.34 and a weighted kappa = 0.35, indicating moderate agreement.

Only the RCT conducted by Guazzoni and colleagues90 was judged to be at low risk of bias for sequence generation and the study by Touijer and colleagues145 was judged to be at low risk for allocation concealment. All other studies were high risk or unclear for these two key domains.

Risk of bias for reported outcomes

The risk of bias assessments for our chosen main outcomes of efficacy (predominantly surgical margins status), urinary incontinence and erectile dysfunction and perioperative adverse events are summarised in Figures 7–10 respectively.

FIGURE 7. Summary of risk of bias assessment for reports of efficacy (n =37).

FIGURE 7

Summary of risk of bias assessment for reports of efficacy (n =37).

FIGURE 8. Summary of risk of bias assessment for reports of urinary dysfunction (n =23).

FIGURE 8

Summary of risk of bias assessment for reports of urinary dysfunction (n =23).

FIGURE 9. Summary of risk of bias assessment for reports of erectile dysfunction (n =20).

FIGURE 9

Summary of risk of bias assessment for reports of erectile dysfunction (n =20).

FIGURE 10. Summary of risk of bias assessment for reports of perioperative safety (n = 35).

FIGURE 10

Summary of risk of bias assessment for reports of perioperative safety (n = 35).

Efficacy

Thirty-seven reports90,93,95,96,98,101,103,105109,112118,122126,128131,134,137,139141,144147 were assessed for risk of bias for efficacy outcomes. Of these, 30 (81%)90,95,96,98,101,103,106,108,113118,122126,128,129,131,137,139141,144147 were considered to be at low risk of bias for confounding factors.

Urinary dysfunction

Twenty-three studies93,95,99,105,106,108,110,112114,116,122,123,126,128130,135137,139,142,146 were assessed for risk of bias for reporting of urinary incontinence outcomes. Of these, 10 (43%)99,108,110,114,116,122,126,128,129,146 were considered to be at low risk of bias for confounding factors.

Erectile dysfunction

Twenty studies93,95,99,106,108,110,112114,116,122,123,126,128,129,135137,142,146 were assessed for risk of bias for reporting of erectile dysfunction. Of these, nine studies (39%)99,110,114,122,126,128,129,135,137 were considered to be at low risk of bias for confounding.

Perioperative safety

Thirty-five studies90,92,93,95,96,98,100,101,104108,111117,119,121126,128,129,131,134,137,139,140,146 were assessed for risk of bias for reporting of perioperative adverse events. Of these, 11 (31%) were judged to be at low risk of bias for confounding factors.90,96,100,106,114,116,122,124126,131

Assessment of effectiveness

Data concerning outcomes included in the meta-analysis are detailed in Tables 6–16. A detailed description of all outcomes abstracted from the included studies is given in tables contained in Appendix 9.

Positive margins

Meta-analysis of data from the 37 included studies90,9498,101,103,105109,112116,118,122,123,125,127,129134,137,139141,143,144,146,147 that reported positive surgical margin rates (Table 6) showed a statistically significant improvement for robotic compared with laparoscopic prostatectomy (OR 0.69; 95% CrI 0.51 to 0.96; probability outcome favours robotic prostatectomy = 0.987). The probability of a positive margin predicted by the mixed-treatment comparison model was 17.0% following robotic prostatectomy compared with 23.6% following laparoscopic prostatectomy. Restriction of the meta-analysis to studies at low risk of bias did not change the direction of effect but did decrease the precision of the effect size (OR 0.73; 95% CrI 0.29 to 1.75), with the probability that the event rate was lower for robotic prostatectomy being no longer statistically significant (p = 0.782).

TABLE 6. Positive margins.

TABLE 6

Positive margins.

Pathological examination of the prostate

Details of the methods described for the handling, processing and pathologist reporting of radical prostatectomy specimens were given in 24 included study reports90,94,96,98,101,103,105,106,109,112, 114,116,118,122,123,134,137141,144 and are summarised in Table 7. In 10 (42%) of these studies reference was made to a published standardised protocol for examination of radical prostatectomy specimens: four studies gave one of three alternative references for the Stanford protocols148150 and one122 specified the Stanford protocol without citing a relevant reference; the remaining studies referenced other protocols published from various centres.82,151153

TABLE 7. Description of pathology methods used to examine the removed prostate for cancer foci.

TABLE 7

Description of pathology methods used to examine the removed prostate for cancer foci.

Concerning established key features of quality-assured pathological examination, 19 (79%) studies described preliminary dyeing of the surface of the prostate to accurately identify the location of the surgical margin. The accepted definition of a positive margin in terms of tumour cells touching or in contact with the dyed prostate surface was specified by 18 (75%) studies; alternative descriptions used were ‘an extension of tumour at the surface of incision’141 and ‘a malignant margin is considered a positive margin’,138 but these studies did not comment on whether or not the specimen was dyed before sectioning. One study defined margin positivity following robotic prostatectomy as ‘cancer seen in the intra-operative distal biopsies’116 whereas a further study reported use of ‘frozen section to control for negative margins’.139 Concerning the methods used to prepare microscope slides (sections) for examination of the prostate gland, the recommended technique of embedding the whole gland for sectioning was specified by nine (38%) studies98,105,106,109,118,123,134,137,140 whereas one (4%) specified systematic partial sampling103 and the sampling method was not specified or unclear in the remaining 14 (58%) studies.90,94,96,101,112,114,116,122,138,141,144,145,147 Section thickness was specified within the recommended range of 2–6 mm in 11 (46%) studies.

The recommended technique of examining sagittal sections from both the apical and the basal slices of the prostate was specified by six (25%) studies.98,103,105,123,134,144 Of the remainder, one study147 used radial sections, two studies137,140 used sagittal sections for the apex only and two studies137,140 used shave margins for both apex and base. No information was given or practice was unclear in the remaining 13 (54%) studies.90,94,96,101,106,112,114,116,118,122,138,139,141

The site of positive margin was specified in six (24%) studies;98,118,134,141,144,147 in four studies118,134,141,147 locations were defined, with some variation in terminology, as apex, base or bladder neck, lateral or posterolateral and multiple and in two further studies98,144 as apex, base, anterior or posterior and apex, base or other. No study gave the extent in millimetres of positive margins in the results.

Given that no studies reported the same methodology for ascertainment of positive margin status it was not possible to undertake a meta-analysis restricted to studies using appropriate methodology.

In summary, these studies showed variation in the pathology protocols employed, which may have affected the determination of positive margin status and thereby increased the risk of bias in the results.

Biochemical recurrence

Biochemical recurrence rates up to 1 year following radical prostatectomy were reported in six studies (Table 8).108,113,115,123,133,137 There was no evidence of a difference in the rates of biochemical recurrence calculated by the mixed-treatment comparison model between robotic and laparoscopic prostatectomy (OR 0.89; 95% CrI 0.24 to 3.34; probability outcome favours robotic prostatectomy = 0.588). Restriction of the meta-analysis to only the studies at low risk of bias was not possible because all studies were at high risk.

TABLE 8. Biochemical recurrence within 12 months.

TABLE 8

Biochemical recurrence within 12 months.

Urinary incontinence

The 22 studies that reported urinary incontinence used a variety of measures at different time points. Measures included observed urinary leakage,93 pad use,91,97,108,112114,116,122,128,129,137,139,146 fluid volume voiding diary130 and validated questionnaire scores [University of California Los Angeles – Prostate Cancer Index (UCLA-PCI)99,110,135,136,142 and International Consultation of Incontinence Questionnaire (ICIQ-UI)106]. Artibani and colleagues123 measured both urinary leakage and pad use. The study conducted by Lama and colleagues133 did not give a definition of incontinence. The results from the 10 studies106,108,113,114,126,128130,133,146 that reported urinary incontinence at a standard time point of 12 months following prostatectomy are given in Table 9. There was no evidence of a difference in the rates of urinary incontinence between robotic and laparoscopic prostatectomy (OR 0.55; 95% CrI 0.09 to 2.84; probability outcome favours robotic prostatectomy = 0.783). Restriction of the meta-analysis to only the studies at low risk of bias was not possible because all studies were at high risk.

TABLE 9. Urinary incontinence at 12 months.

TABLE 9

Urinary incontinence at 12 months.

The study conducted by Carlsson and colleages104 reported 7/1253 (0.6%) patients requiring further postoperative surgery for incontinence between 30 days and 15 months after their initial robotic operation compared with 11/485 (2.2%) requiring further postoperative surgery for incontinence after undergoing an open radical prostatectomy.

Erectile dysfunction

As described in Overview of type of outcomes reported, a total of 19 studies provided data on sexual function. The time point following surgery when the outcome was assessed and the measure used to quantify the outcome varied between studies. Erectile dysfunction was variously defined as the inability to achieve and maintain a spontaneous or drug-assisted erection suitable for sexual intercourse93,108,113,114,116,122,123,126,129 or by validated symptom questionnaire scores [UCLA-PCI,99,110,135,136,142 IIEF-5106,128 Expanded Prostate Cancer Index Composite, sexual function subscale (EPIC-SFSS)146 and Sexual Health Inventory for Men (SHIM)112]. The study conducted by Lama and colleagues133 did not report a definition of erectile dysfunction. Given the diversity of definitions and types of data (continuous and dichotomous) it was not possible to collate data from individual studies into a form suited to meta-analysis. Of the two studies directly comparing robotic and laparoscopic prostatectomy that reported erectile dysfunction, one99 showed earlier recovery of sexual function following the robotic prostatectomy procedure, with 35% compared with 21% returning to baseline functioning at 3 months post surgery and 43% compared with 25% returning to baseline functioning at 6 months, and the other93 favoured laparoscopic prostatectomy (46% required drug aid vs 36% at 3 months in the robotic and laparoscopic groups, respectively).

Quality of life

Quality of life following prostatectomy as measured by validated patient-reported questionnaires was reported in 10 studies: European Quality of Life-5 Dimensions (EQ-5D) visual analogue scale (VAS); 90,116,139 Short Form questionnaire-36 items (SF-36);135,136 Short Form questionnaire-12 items (SF-12);111 European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30);137 the quality-of-life item contained within the International Prostate Symptom Score (I-PSS);130 the International Continence Society (ICS)91 and the Expanded Prostate Cancer Index Composite urinary incontinence and sexual function subscales (EPIC-UISS-SFSS).146 Full details are given in Appendix 9. Quality-of-life measurements following robotic prostatectomy were reported by two studies111,116 with a maximum observation period of 6 weeks. The data were insufficient to enable us to assess any difference in quality of life following robotic or laparoscopic prostatectomy. Three studies135137 reported that preoperative physical functioning level was not achieved in all patients by 6 months postoperatively but the clinical significance of the differences was unclear.

Pain

There were no direct comparative studies of robotic and laparoscopic procedures reporting pain. It was therefore not possible to report any difference in pain between the procedures either postoperatively or in the long term.

Need for further cancer treatment

Dahl and colleagues126 was the only report that included information on the numbers of men requiring further treatment for cancer persistence or recurrence, with rates of 5/104 (5%) for laparoscopic prostatectomy and 2/102 (2%) for open prostatectomy.

Death

Four studies104,105,126,140 reported deaths resulting from complications in the 30-day postoperative period. These included two fatal cardiac arrests104,126 and one cerebrovascular accident105 following open prostatectomy. Salomon and colleagues140 also reported one death due to pulmonary embolism following laparoscopic prostatectomy. Five studies92,95,96,137,154 involving 1600 men specifically reported no postoperative deaths. Drouin and colleagues101 reported one death due to prostate cancer 5 years after open prostatectomy and four deaths due to cardiovascular complications without specifying which procedure these men had received. Krambeck and colleagues108 reported all-cause mortality rates of 4/248 (1.6%) for men undergoing robotic prostatectomy and 4/492 (0.8%) after open prostatectomy at a median follow-up time of 1.3 years.

Perioperative adverse events

Data on the perioperative adverse events of blood transfusion, anastomotic leak, bladder neck contracture, wound infection, organ injury, ileus, deep-vein thrombosis and pulmonary embolism are presented in Tables 10–17. Abstracted data concerning other specific adverse events not included in the meta-analysis are detailed in Appendix 10. All adverse events were additionally categorised according to the Clavien–Dindo system and the data meta-analysed according to Clavien–Dindo score (see Tables 59–70).

Blood transfusion

Meta-analysis of data from the 30 studies9092,9496,100,101,104108,112,113,116,119123,125,127129,132134,137,140 that reported blood transfusion rates (Table 10) showed a relative reduced need for blood transfusion with robotic prostatectomy compared with laparoscopic prostatectomy (OR 0.71; 95% CrI 0.31 to 1.62) but this was not statistically significant (probability outcome favours robotic prostatectomy = 0.780). The predicted rate of blood transfusion in the mixed-treatment comparison model was 3.5% for robotic prostatectomy and 5% for laparoscopic prostatectomy. Restriction of the meta-analysis to the studies at low risk of bias changed the direction of effect to favour the laparoscopic procedure but precision was reduced (OR 1.45; 95% CrI 0.38 to 6.21; probability that outcome favours laparoscopic prostatectomy = 0.257).

TABLE 10. Blood transfusion.

TABLE 10

Blood transfusion.

Bladder neck contracture

Meta-analysis of data from the 13 studies92,104,106,108,112,113,124126,128,133,139,146 reporting bladder neck contracture (Table 11) showed a reduced rate for men undergoing robotic prostatectomy but this was not statistically significant (probability outcome favours robotic prostatectomy = 0.805). The predicted event probability in the mixed-treatment comparison model was 1% for robotic and 2.2% for laparoscopic prostatectomy. Restriction of the meta-analysis to only the studies at low risk of bias was not possible because all studies were categorised as high risk.

TABLE 11. Bladder neck contracture.

TABLE 11

Bladder neck contracture.

Anastomotic leak

Meta-analysis of data from 14 studies90,94,96,97,101,104,112,113,125,126,128,134,139,140 that reported anastomotic leak (Table 12) showed a statistically significant reduced rate of anastomotic leaks in men following robotic prostatectomy (OR 0.21; 95% CrI 0.05 to 0.76; probability outcome favours robotic prostatectomy = 0.990). Predicted probability of this event in the model was 1.0% following robotic and 4.4% following laparoscopic prostatectomy. Restriction of the meta-analysis to only studies at low risk of bias was not possible because the zero event rate in the robotic studies produced unstable model convergence.

TABLE 12. Anastomotic leak.

TABLE 12

Anastomotic leak.

Wound or urinary infection

Meta-analysis of data from 12 studies92,96,101,104,108,116,123,125128,140 that reported infection rates (Table 13) showed a reduction in the rate of this event after robotic prostatectomy compared with laparoscopic prostatectomy but this was not statistically significant (probability outcome favours robotic prostatectomy = 0.662). The probability of an infection predicted by the model was 0.8% following robotic prostatectomy and 1.1% for laparoscopic prostatectomy. Restriction of the meta-analysis to only the studies at low risk of bias changed the direction of effect but precision was reduced.

TABLE 13. Infection.

TABLE 13

Infection.

Organ injury

In descending order of frequency the reported injuries affected the rectum, ureter and bowel. Meta-analysis of data from the 17 studies93,101,104106,113,116,123125,127129,133,134,139,140 that reported organ injuries (Table 14) showed a reduction in the event rate following the robotic procedure that was statistically significant (OR 0.16; 95% CrI 0.03 to 0.76; probability outcome favours robotic prostatectomy = 0.987). The event probability predicted by the model was 0.4% for robotic prostatectomy and 2.9% for laparoscopic prostatectomy. Restriction of the meta-analysis to only the studies at low risk of bias maintained the direction and magnitude of effect.

TABLE 14. Organ injury.

TABLE 14

Organ injury.

Ileus

Meta-analysis of data from 12 studies92,95,106,108,112,116,123,125,128,134,139,140 that reported ileus (slowness of recovery of bowel function) rates (Table 15) showed a reduction in the event rate following the robotic procedure that was not statistically significant (OR 0.46; 95% CrI 0.12 to1.51; probability outcome favours robotic prostatectomy = 0.920). The predicted probability of ileus was 1.1% with the robotic procedure and 2.4% with the laparoscopic procedure. This difference should be treated with caution given that one study92 contributed one-third of all data. Restriction of the meta-analysis to only the studies at low risk of bias was not possible because all studies were categorised as high risk.

TABLE 15. Ileus.

TABLE 15

Ileus.

Deep-vein thrombosis

Meta-analysis of data from eight studies that reported deep-vein thrombosis rates (Table 16) showed an increased risk following the robotic procedure that was not statistically significant (OR 2.67; 95% CrI 0.26 to 50.3; probability outcome favours robotic prostatectomy = 0.193). The predicted probability of a deep-vein thrombosis was 0.6% with the robotic procedure and 0.2% with the laparoscopic procedure. Restriction of the meta-analysis to only the studies at low risk of bias was not possible because all studies were categorised as high risk.

TABLE 16. Deep-vein thrombosis.

TABLE 16

Deep-vein thrombosis.

Pulmonary embolism

Because of the low event rate and the small number of studies reporting this outcome (Table 17) meta-analysis was not possible. Using crude combining of events across all studies, the percentage of men suffering pulmonary emboli was 2/1634 (0.1%) for robotic prostatectomy and 2/392 (0.5%) for laparoscopic prostatectomy.

TABLE 17. Pulmonary embolism.

TABLE 17

Pulmonary embolism.

Clavien–Dindo scores

The predicted event rates based on the meta-analysis statistical models for each Clavien–Dindo category are shown in Table 18. The individual study data contributing to each meta-analysis are given in Appendix 9. The OR for each Clavien–Dindo score was in favour of the robotic procedure but only that for Clavien IIIb, adverse event requiring intervention under general anaesthesia, was statistically significant (Figure 11).

TABLE 18. Predicted rates of event for each Clavien–Dindo score.

TABLE 18

Predicted rates of event for each Clavien–Dindo score.

FIGURE 11. Odds ratio and 95% CrI by Clavien–Dindo score.

FIGURE 11

Odds ratio and 95% CrI by Clavien–Dindo score.

Descriptors of care

Equipment failure

Two studies reported equipment failure affecting the performance of the prostatectomy equipment. Menon and colleagues95 reported eight initial problems with the voice recognition system of the voice-controlled AESOP camera holder (Computer Motion, Goleta, CA, USA) during laparoscopic prostatectomy while Hu and colleagues92 reported two cases of equipment malfunction during robotic prostatectomy.

Conversion to open surgery

Meta-analysis of data from the 17 studies that reported rates of conversion from robotic or laparoscopic to open prostatectomy surgery (Table 19) showed lower rates for robotic prostatectomy but the difference was not statistically significant (OR 0.28; 95% CrI 0.03 to 2.00; probability outcome favours robotic prostatectomy = 0.893). The rate of conversion to open surgery predicted by the model was 0.3% with the robotic procedure and 0.9% with the laparoscopic procedure. Restriction of the meta-analysis to only the studies at low risk of bias was not possible because all studies were categorised as high risk.

TABLE 19. Conversion to open surgery.

TABLE 19

Conversion to open surgery.

Operation time

The criteria used to define and measure operation time varied considerably between studies and are detailed in Appendix 9. To attempt to minimise the effect of substantive variation between studies, meta-analysis was restricted to eight studies that directly compared robotic and laparoscopic operation times (Table 20). The pooled estimate demonstrated a statistically significant reduction in operation time of −12.4 minutes (95% CrI −16.5 minutes to −8.1 minutes) in favour of robotic prostatectomy. This difference should be treated with caution given uncertainty in whether robot docking time before commencing the surgery was included in the measured operation time in all studies.

TABLE 20. Operation time in minutes – directly comparative studies only.

TABLE 20

Operation time in minutes – directly comparative studies only.

Duration of catheterisation

Postoperative catheterisation policies varied considerably across the 23 studies90,91,94,96,101,105,106,113,114,116,122124,127,129,131134,137,139,140,143 that included relevant details and no meta-analysis was possible given the diversity of type of summary outcome measures reported. Of the four directly comparative studies of robotic and laparoscopic procedures, two94,96 reported a shorter duration of catheterisation in men undergoing laparoscopic prostatectomy and two91,101 reported a shorter duration of catheterisation for robotic prostatectomy. Only the report by Gosseine and colleagues92 showed that the difference in duration of catheterisation was statistically significant, being 1.5 days shorter for robotic prostatectomy (p = 0.01).

Length of hospital stay

Length of hospital stay varied considerably across the 28 studies91,96,97,102,105108,112114,116,119,121,123128, 131134,137140,143 that gave this information and no meta-analysis was possible given the diversity of type of summary outcome measures reported. Of the four studies directly comparing robotic and laparoscopic prostatectomy,91,96,97,102 two reported a 1-day shorter length of stay for laparoscopic prostatectomy and two reported a 1-day shorter length of stay for robotic prostatectomy; none demonstrated any statistical significance.

Assessment of the learning curve

The variables of numbers of surgeons acting as lead operator, the number of procedures conducted by each surgeon prior to study commencement, the number of procedures carried out by each surgeon during the study and reported outcomes used to assess learning were abstracted from each included study (see Appendix 9). In general, the extent of reporting of relevant data on these variables was limited and data were often not given in a clear form suited to meta-analysis. The number of surgeons performing the surgery on men included in each study for both procedures was reported in 43/58 (74%) studies (see Appendix 9). Of these, nine90,91,97,105,109,112,113,128,134 were single-surgeon studies. Studies that provided information on surgeons' previous experience did so in a number of different ways including using categories such as ‘experienced’, ‘fellowship trained’ or ‘performed radical retropubic prostatectomies for 15 years prior to study’.

We focused on the rate of positive surgical margins as the key outcome to assess the effect of increasing surgeon experience to maintain consistency with the findings of the systematic review and the importance of this outcome to the economic modelling (see Chapter 5). The proportion of positive surgical margins for robotic and laparoscopic radical prostatectomy was plotted against the number of procedures carried out by the participating surgeons in each included study (Figure 12). Regression modelling illustrated that there was no evidence of trends across increasing experience (the dashed line is the predicted linear relationship for laparoscopic studies and the solid line is the predicted linear relationship for robotic studies), with R2 < 0.02%, demonstrating no statistical significance.

FIGURE 12. Proportion of positive surgical margins with increasing experience in included studies.

FIGURE 12

Proportion of positive surgical margins with increasing experience in included studies.

No data on parameters of the ‘shape’ of the learning curve, such as rates of positive margins for set number of cases performed, were identified in the included comparative studies. The inclusion criteria were therefore extended to include case series of laparoscopic and robotic radical prostatectomy that included more than 200 men. This specific extended search identified six robotic case series and four laparoscopic case series (Table 21). Two studies155,156 reported only a mathematical shape to the learning curve, thereby precluding any formal modelling of the learning curve parameters (starting point, rate of learning and asymptote). All studies reported a decrease in positive surgical margin rate with increasing surgeon experience except for that by Eden and colleagues157 who reported a consistently low rate throughout the series of men undergoing laparoscopic prostatectomy. The positive margin rate data plotted against the first and last reported level of experience for each case series are shown in Figure 13. There was some evidence that a non-linear (logarithmic) relationship with increasing experience fitted the data better than a linear relationship; however, this was not statistically significant (log-experience −0.02; 95% CI −0.043 to 0.003; p = 0.08). This equated to an average surgical margin rate of 25.6% at case one, reducing to 14.5% by 250 cases and 11.7% by 1000 cases. The data provided no evidence that learning contributed differently to positive margin rates between the two procedures (mean difference in level −0.02; 95% CI −0.16 to 0.12; p = 0.755).

TABLE 21. Summary of learning curve measures in case series.

TABLE 21

Summary of learning curve measures in case series.

FIGURE 13. Proportion of positive surgical margins with increasing experience in case series.

FIGURE 13

Proportion of positive surgical margins with increasing experience in case series.

To summarise the results, the two approaches to assessing whether or not surgeon learning affected the rate of positive margins gave conflicting findings. Across the studies included in the meta-analyses of positive margin rates, there was no evidence that experience contributed as a significant confounder to the results, whereas the larger case series suggested a reduction over time in positive margin rates. There was no empirical evidence, however, that the rate of learning differed between the two surgical procedures. Caution is therefore required in the interpretation of these findings.

Summary and conclusions of the evidence of comparative effectiveness

This review considered data from 19,064 patients across one RCT and 53 non-randomised comparative studies with very few studies considered at low risk of bias. Results should be interpreted cautiously to reflect the poor quality of the evidence base and the variation in definitions of outcomes. It was noteworthy that, when meta-analyses were restricted to studies assessed to be at low risk of bias, the effect sizes tended to move from favouring robotic prostatectomy towards no difference. There were limited published data on long-term efficacy of robotic and laparoscopic radical prostatectomy in reducing morbidity and no data comparing mortality from prostate cancer. We found no evidence for any difference in patient-reported outcomes. There was strong statistical evidence that positive surgical margin rates, a proxy measure for cancer control, may be reduced by the use of robotic radical prostatectomy; however, it was unclear in the literature how these differences impact on cancer recurrence and long-term efficacy outcomes and restricting the analysis to low risk of bias studies showed no statistical evidence of a difference. This finding should therefore be interpreted with caution. In addition, the studies showed variation in the pathology protocols employed, which may have biased the determination of positive margin status and prevented accurate comparison between studies. Improvement in reporting pathology findings is necessary if evidence syntheses across studies are to be undertaken. The recent ISUP Consensus Conference72 aims to promote consistency in the handling and reporting of radical prostatectomy specimens and provide detailed guidelines that are feasible for most practising pathologists to implement and may be a major advance towards providing more comparable data in the published literature.

There was a general trend for robotic surgery to have fewer perioperative adverse events, apart from rarely reported deep-vein thrombosis, and the differences reached statistical significance for anastomotic leak and organ injury in particular, and those classified as Clavien IIIb in general. There were limited data on the important longer-term functional adverse effects of urinary incontinence and erectile dysfunction. The available data suggested no evidence of a difference in the proportion of men suffering urinary incontinence at 12 months. There were insufficient data to draw any conclusions on the likely size of any differential effect on rates of erectile dysfunction.

There was conflicting evidence on the impact of the learning curve for both procedures. There was no evidence that experience contributed as a significant confounder to the meta-analysis results, but case series data suggested a reduction over time in positive margin rates. There was, however, no empirical evidence that the rate of learning as expressed by changes in positive margin rates differed between the two surgical procedures and therefore little support for including the learning curve relationship in the base-case economic model.

Clinical effect size

A summary of the clinical effect sizes for all outcomes derived from the meta-analyses for which data were available is given in Figure 14. This should be interpreted in light of the comments made earlier in the chapter.

FIGURE 14. Summary of the clinical effect sizes (ORs and 95% CrIs) from meta-analyses.

FIGURE 14

Summary of the clinical effect sizes (ORs and 95% CrIs) from meta-analyses. To improve visual display the upper CrI has been truncated to 5.0. Low RoB denotes estimate from low risk of bias studies only.