Tag Archive for: open radical prostatectomy

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It’s not about the machine, stupid

Robotic surgery trial exposes limitations of randomised study design

 

Here it is, the highly anticipated randomised controlled trial of open versus robotic radical prostatectomy published today in The Lancet. Congratulations to the team at Royal Brisbane Hospital for completing this landmark study.


DM1


The early headlines around the world include everything from this one in the Australian Financial Review:

DM2b      –   to this from The Telegraph in London

DM3bAs ever, there will be intense and polarising discussion around this. One might expect that a randomised controlled trial, a true rarity in surgical practice, might settle the debate here; however, it is already clear that there will be anything BUT agreement on the findings of this study. Why is this so? Well let’s look first at what was reported today.

 

Study design and findings:

This is a prospective randomised trial of patients undergoing radical prostatectomy for localised prostate cancer. Patients were randomised to undergo either open radical prostatectomy (ORP, n=163) or robotic-assisted radical prostatectomy (RARP, n=163). All ORPs were done by one surgeon, Dr John Yaxley (JY), and all RARPs were done by Dr Geoff Coughlin (GC). The hypothesis was that patients undergoing RARP would have better functional outcomes at 12 weeks, as measured by validated patient-reported quality of life measures. Other endpoints included positive surgical margins and complications, as well as time to return to work.

So what did they find? In summary, the authors report no difference in urinary and sexual function at 12 weeks. There was also no statistical difference in positive surgical margins. RARP patients had a shorter hospital stay (1.5 vs 3.2days, p<0.0001) and less blood loss (443 vs 1338ml, P<0.001), and less pain post-operatively, yet, these benefits of minimally-invasive surgery did not translate into an earlier return to work. The average time to return to work in both arms was 6 weeks.

The authors therefore conclude by encouraging patients “to choose an experienced surgeon they trust and with whom they have a rapport, rather than choose a specific surgical approach”. Fair enough.

In summary therefore, this is a randomised controlled trial of ORP vs RARP showing no difference in the primary outcome. One might reasonably expect that we might start moth-balling these expensive machines and start picking up our old open surgery instruments. But that won’t happen, and my prediction is that this study will be severely criticized for elements of its design that explain why they failed to meet their primary endpoint.

 

Reasons why this study failed:

1.      Was this a realistic hypothesis? No it was not. For those of us who work full-time in prostate cancer, the notion that there would be a difference in sexual and urinary function at 12 weeks following ORP or RARP is fanciful. It is almost like it was set up to fail. There was no pilot study data to encourage such a hypothesis, and it remains a mystery to me why the authors thought this study might ever meet this endpoint. I hate to say “I told you so”, but this hypothesis could never have been proved with this study design.

2.      There is a gulf in surgical experience between the two arms. The lack of equipoise between the intervention arms is startling, and of itself, fully explains the failure of this study to meet its endpoints. I should state here that both surgeons in this study, JY (“Yax”) and GC (“Cogs”), are good mates of mine, and I hold them in the highest respect for undertaking this study. However, as I have discussed with them in detail, the study design which they signed up to here does not control for the massive difference in radical prostatectomy experience that exists between them.  Let’s look at this in more detail:

  1.        ORP arm: JY was more than 15 years post-Fellowship at the start of this study, and had completed over 1500 ORP before performing the first case in the trial.
  2.       RARP arm: GC was just two years post-Fellowship and had completed only 200 RARP at the start of the study.

The whole world knows that surgeon experience is the single most important determinant of outcomes following radical prostatectomy, and much data exists to support this fact. In the accompanying editorial, Lord Darzi reminds us that the learning curve for functional and oncological outcomes following RARP extends up to 700 cases. Yes 700 cases of RARP!! And GC had done 200 radical prostatectomies prior to operating on the first patient in this study. Meanwhile his vastly more experienced colleague JY, had done over 1500 cases. The authors believe that they controlled for surgeon heterogeneity based on the entry numbers detailed above, and state that it is “unlikely that a learning curve contributed substantially to the results”. This is bunkum. It just doesn’t stack up, and none of us who perform this type of surgery would accept that there is not a clinically meaningful difference in the experience of a surgeon who has performed 200 radical prostatectomies, compared with one who has performed 1500. Therein lies the fundamental weakness of this study, and the reason why it will be severely criticized. It would be the equivalent of comparing 66Gy with 78Gy of radiotherapy, or 160mg enzalutamide with 40mg – the study design is simply not comparing like with like, and the issue of surgeon heterogeneity as a confounder here is not accounted for.

3.      Trainee input is not controlled for – most surprisingly, the authors previously admitted that “various components of the operations are performed by trainee surgeons”. One would expect that with such concerns about surgeon heterogeneity, there should have been tighter control on this aspect of the interventions. It would have been reasonable within an RCT to reduce the heterogeneity as much as possible by sticking to the senior surgeons for all cases.

Having said all that, John and Geoff are to be congratulated for the excellent outcomes they have delivered to their patients in both arms of this study. These are excellent outcomes, highly credible, and represent, in my view, the best outcomes to be reported for patients undergoing RP in this country. We are all too familiar with completely unbelievable outcomes being reported for patients undergoing surgery/radiotherapy/HIFU etc around the world, and we have a responsibility to make sure patients have realistic expectations. John and Geoff have shown themselves to be at the top of the table reporting these credible outcomes today.

 

“It’s about the surgeon, stupid”

To paraphrase that classic phrase of the Clinton Presidential campaign of 1992, this study clearly demonstrates that outcomes following radical prostatectomy are about the surgeon, and not about the robot. Yet one of the co-authors, a psychologist, comments that, “at 12 weeks, these two surgical approaches yielded similar outcomes for prostate cancer patients”. Herein lies one of the classic failings of this study design, and also a failure of the investigators to fully understand the issue of surgeon heterogeneity in this study. It is not about the surgical approach, it is about the surgeon experience.

If the authors had designed a study that adequately controlled for surgeon experience, then it may have been possible for the surgical approach to be assessed with some equipoise. It is not impossible to do so, but is certainly challenging. For example a multi-centre study with multiple surgeons in each arm would have helped balance out the gulf in surgical experience in this two-surgeon study. Or at the very least, the authors should have ensured that they were comparing apples with apples by having a surgeon with in excess of 1500 RARP experience in that arm. Another approach would have been to get a surgeon with huge experience of both procedures (eg Dr Smith at Vanderbilt who has performed >3000 RARP and >3000 ORP), and to randomise patients to be operated on only by a single surgeon with such vast experience. That would have truly allowed the magnitude of the surgical approach effect to be measured, without the bias inherent in this study design.

 

Robotic surgery bridges the experience gap:

Having outlined these issues with surgeon heterogeneity and lack of equipoise, there is another angle which my colleague Dr Daniel Moon has identified in his comments in the Australian media today and which should be considered.

Although this is a negative study which failed to meet its primary endpoints, it does demonstrate that a much less experienced surgeon can actually deliver equivalent functional and oncological outcomes to a much more experienced surgeon, by adopting a robotic approach. Furthermore, his patients get the benefits of a minimally-invasive approach as detailed in the paper. This therefore demonstrates that patients can be spared the inferior outcomes that may be delivered by less experienced surgeons while on their learning curve, and the robotic approach may therefore reduce the learning curve effect.

On that note, a point to consider would be what would JY’s outcomes have been in this study if he had 13 years and 1300 cases less experience to what he had entering this study? Would the 200 case experience-Yax have been able to match the 1500 case experience-Yax?? Surely not.

And finally, just as a footnote for readers around the world about what is actually happening on the ground following this study. During the course of this study, the ORP surgeon JY transitioned to RARP, and this is what he now offers almost exclusively to his patients. Why is that? It is because he delivers better outcomes by bringing a robotic approach to the vast surgical experience that he also brings to his practice, and which is of course the most important determinant of better outcomes.

Sadly, “Yax” and “Cogs”, the two surgeons who operated in this study, have been prevented from speaking to the media or to being quoted in or commenting on this blog, but we are looking forward to hearing from them when they present this data at the Asia-Pacific Prostate Cancer Conference in Melbourne in a few weeks.

 

Declan G Murphy
Associate Editor BJUI; Urologist & Director of Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

Twitter: @declangmurphy

 

 

 

Article of the month: The race to urinary continence after RP

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by prominent members of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Inge Geraerts discussing functional outcomes after ORP and RARP.

If you only have time to read one article this week, it should be this one.

Prospective evaluation of urinary incontinence, voiding symptoms and quality of life after open and robot-assisted radical prostatectomy

Inge Geraerts*, Hendrik Van Poppel†, Nele Devoogdt*‡, Ben Van Cleynenbreugel†, Steven Joniau† and Marijke Van Kampen*‡

Departments of *Rehabilitation Science, †Urology and ‡Physical Medicine and Rehabilitation, UZ Leuven, Leuven, Belgium

Read the full article
OBJECTIVE

• To compare functional outcomes, i.e. urinary incontinence (UI), voiding symptoms and quality of life, after open (ORP) and robot-assisted radical prostatectomy (RARP).

PATIENTS AND METHODS

• Between September 2009 and July 2011, 180 consecutive patients underwent radical prostatectomy; of these, 116 underwent ORP and 64 underwent RARP. We prospectively assessed the functional outcomes of each group during the first year of follow-up.

• We measured UI on the 3 days before surgery (24-h pad test) and daily after surgery until total continence, defined as 3 consecutive days of 0 g urine leak, was achieved. Additionally, all patients were assessed before surgery and at 1, 3, 6 and 12 months after surgery using the International Prostate Symptom Score (IPSS) and the King’s Health Questionnaire (KHQ).

• All patients received pelvic floor muscle training until continence was achieved.

• Kaplan–Meier analyses and Cox regression with correction for covariates were used to compare time to continence. A Mann–Whitney U-test was used to assess IPSS and KHQ.

RESULTS

• Patients in the RARP group had a significantly lower D’Amico risk group allocation and underwent more nerve-sparing surgery. Other characteristics were similar.

• Patients in the RARP group regained continence sooner than those in the ORP group (P = 0.007). In the RARP group, the median time to continence (16 vs 46 days, P = 0.026) was significantly shorter and the median amount of first day UI (44 vs 186 g, P < 0.01) was significantly smaller than in the ORP group. After correction for all covariates, the difference remained significant (P = 0.036, hazard ratio [HR] 1.522 (1.027–2.255). In addition, younger men, men with positive surgical margins and men without preoperative incontinence achieved continence sooner.

• A comparison of time to continence between groups with a sufficient number of patients (intermediate risk and/or bilateral nerve-sparing) still showed a faster return of continence after RARP, but the effect decreased in size and was nonsignificant (HR>1.2, P> 0.05).

• Only six patients (two in the RARP and four in the ORP group) still had UI after 1 year.• Patients in the RARP group had significantly better IPSS scores at 1 (P = 0.013) and 3 (P = 0.038) months, and scored better in almost all KHQ aspects.

CONCLUSION

• In this prospective trial, patients treated with RARP tended to regain urinary continence sooner than patients treated with ORP, but in subgroup analyses statistical significance disappeared and effect size decreased dramatically, indicating that the results must be interpreted with caution.

 

Read Previous Articles of the Week

 

Editorial: Regaining continence after radical prostatectomy: RARP vs. ORP

Functional outcomes represent relevant criteria to evaluate the success of radical prostatectomy (RP) in the treatment of localised and locally advanced prostate cancer. Indeed, while the primary goal of RP remains the complete extirpation of the primary tumour, patients’ satisfaction can be negatively affected by urinary incontinence and/or erectile dysfunction after RP.

In this issue of BJUI, Geraerts et al. [1] evaluated urinary continence recovery and voiding symptoms in a well-conducted, single-centre, prospective non-randomised study comparing two contemporary series of patients who underwent either open retropubic RP (RRP) or robot-assisted RP (RARP) for clinically localised or locally advanced prostate cancer. Patients were assigned to each group according to their or their surgeon’s preference. High-risk prostate cancers were preferably treated with an open access to offer a more accurate extended lymphadenectomy. The study showed that the urinary continence recovery rate was significantly shorter in the RARP group than in the RRP group (16 vs 46 days; P = 0.008). Interestingly, the RA approach remained an independent predictor of time to urinary continence recovery on multivariable Cox regression analysis (P = 0.03; hazard ratio [HR] 1.52, 95% CI 1.03–2.26). Therefore, this study confirmed previously published results. In 2003, Tewari et al. [2] reported a shorter time to recovery of urinary continence in patients who underwent RARP (44 days) than those who received RRP (160 days). In 2008, Kim et al. [3] reported a median time to continence in RARP patients of 1.6 months, significantly lower than the 4.3 months in the RRP patients. Interestingly, Geraerts et al. [1] identified other independent predictors of time to continence, such as patient’s age >65 years (P = 0.02; HR 0.67, 95% CI 0.45–0.96) and the preoperative continence status (P = 0.004; HR 1.69, 95% CI 1.18–2.43). In all, 28% of patients who received RRP and 34% of those who underwent RARP were preoperatively defined as incontinent using a symptom-specific questionnaire [1]. These patients classifiable as ‘Cx’ according to the Survival, Continence and Potency (SCP) classification [4] represent a confounding population in the Geraerts et al. study who should be evaluated separately.

An interesting question is whether the reported difference in time to continence in favour of RARP is also significant from the clinical perspective. Urinary continence in patients who underwent RARP recovered 1 month early than those treated with traditional RRP. The King’s Health questionnaire seems to confirm a positive effect of this outcome on the patient’s quality of life (QoL). Indeed, there were better results in the RARP compared with RRP group at 1 and 3 months after RP. Moreover, at 12 months after RP, patients who underwent RRP were more physically limited (P = 0.01) and took more precautions to avoid urine loss (P = 0.01) than those who received a RARP [1]. These data seem to be in conflict with the reported overlapping 12-month urinary continence rates (96% in RRP and 97% in RARP group). Moreover, looking at the 12-month urinary continence rate, the Geraerts et al. study does not confirm the results of a recent cumulative analysis of available comparative studies showing a better 12-month urinary continence rate after RARP compared with RRP (odds ratio 1.53; P = 0.03) [1].

Interestingly, the 12-month urinary continence rate reported after RRP by Geraerts et al. is significantly higher (96%) than the values reported in the comparative studies included in the meta-analysis (88.7%) and in the most important and recent RRP non-comparative series (60–93%) [5]. This aspect appears to confirm the important role of surgeon experience. Indeed, in this Belgium series most of the open procedures were performed by an expert surgeon with experience of >3000 RRPs, and thus able to reach excellent functional outcomes for urinary continence recovery. In favour of robotic surgeons, we could consider that they were able to reach overlapping results after <200 cases.

In conclusion, the study published by Geraerts et al. [1] showed that modern RP in expert hands is able to achieve excellent results for urinary continence recovery regardless of the approach. However, pure and RA laparoscopy has pushed open surgeons to improve technical and postoperative aspects to achieve comparable outcomes. RARP can offer some advantages over traditional RRP, above all for the time to reach urinary continence. This advantage seems to have generated a better QoL profile in patients who underwent RARP at 12 months after RP.

However, the choice between the two techniques must be taken according to all the most relevant parameters including perioperative, functional (continence and potency) and oncological outcomes. Therefore, we strongly support the publication of clinical series or comparative studies reporting results according to the ‘trifecta’, ‘pentafecta’ or SCP systems [6].

Vincenzo Ficarra°, Alessandro Iannettiand Alexandre Mottrie
OLV Vattikuti Robotic Surgery Institute, Aalst, Belgium, °Department of Experimental and Clinical Medical Sciences – Urology Unit – School of Medicine, University of Udine, 
and *Department of Surgical, Oncologic and Gastrointestinal Sciences, Padua, Italy

Read the full article

References

  1. Geraerts I, Van Poppel H, Devoogdt N, Van Cleynenbreugel B, Joniau S, Van Kampen M. Prospective evaluation of urinary incontinence, voiding symptoms and quality of life after open and robot-assisted radical prostatectomyBJU Int 2013; 112:936–943
  2. Tewari A, Srivasatava A, Menon M, Members of the VIP Team. A prospective comparison of radical retropubic and robot-assisted prostatectomy: experience in one institutionBJU Int 2003; 92: 205–210
  3. Kim SC, Song C, Kim W et al. Factors determining functional outcomes after radical prostatectomy: robot-assisted versus retropubicEur Urol 2011; 60: 413–419
  4. Ficarra V, Sooriakumaran P, Novara G et al. Systematic review of methods for reporting combined outcomes after radical prostatectomy and proposal of a novel system: the survival, continence, and potency (SCP) classificationEur Urol 2012; 61:541–548
  5. Ficarra V, Novara G, Rosen RC et al. Systematic review and meta-analysis of studies reporting urinary continence recovery after robot-assisted radical prostatectomyEur Urol 2012; 62: 405–417
  6. Ficarra V, Borghesi M, Suardi N et al. Long-term evaluation of survival, continence and potency (SCP) outcomes after robot-assisted radical prostatectomy (RARP)BJU Int 2013; 112: 338–345

Video: Functional outcomes after ORP and RARP

Prospective evaluation of urinary incontinence, voiding symptoms and quality of life after open and robot-assisted radical prostatectomy

Inge Geraerts*, Hendrik Van Poppel, Nele Devoogdt*, Ben Van Cleynenbreugel, Steven Joniau and Marijke Van Kampen*

Departments of *Rehabilitation Science, Urology and Physical Medicine and Rehabilitation, UZ Leuven, Leuven, Belgium

Read the full article
OBJECTIVE

• To compare functional outcomes, i.e. urinary incontinence (UI), voiding symptoms and quality of life, after open (ORP) and robot-assisted radical prostatectomy (RARP).

PATIENTS AND METHODS

• Between September 2009 and July 2011, 180 consecutive patients underwent radical prostatectomy; of these, 116 underwent ORP and 64 underwent RARP. We prospectively assessed the functional outcomes of each group during the first year of follow-up.

• We measured UI on the 3 days before surgery (24-h pad test) and daily after surgery until total continence, defined as 3 consecutive days of 0 g urine leak, was achieved. Additionally, all patients were assessed before surgery and at 1, 3, 6 and 12 months after surgery using the International Prostate Symptom Score (IPSS) and the King’s Health Questionnaire (KHQ).

• All patients received pelvic floor muscle training until continence was achieved.

• Kaplan–Meier analyses and Cox regression with correction for covariates were used to compare time to continence. A Mann–Whitney U-test was used to assess IPSS and KHQ.

RESULTS

• Patients in the RARP group had a significantly lower D’Amico risk group allocation and underwent more nerve-sparing surgery. Other characteristics were similar.

• Patients in the RARP group regained continence sooner than those in the ORP group (P = 0.007). In the RARP group, the median time to continence (16 vs 46 days, P = 0.026) was significantly shorter and the median amount of first day UI (44 vs 186 g, P < 0.01) was significantly smaller than in the ORP group. After correction for all covariates, the difference remained significant (P = 0.036, hazard ratio [HR] 1.522 (1.027–2.255). In addition, younger men, men with positive surgical margins and men without preoperative incontinence achieved continence sooner.

• A comparison of time to continence between groups with a sufficient number of patients (intermediate risk and/or bilateral nerve-sparing) still showed a faster return of continence after RARP, but the effect decreased in size and was nonsignificant (HR>1.2, P> 0.05).

• Only six patients (two in the RARP and four in the ORP group) still had UI after 1 year.• Patients in the RARP group had significantly better IPSS scores at 1 (P = 0.013) and 3 (P = 0.038) months, and scored better in almost all KHQ aspects.

CONCLUSION

• In this prospective trial, patients treated with RARP tended to regain urinary continence sooner than patients treated with ORP, but in subgroup analyses statistical significance disappeared and effect size decreased dramatically, indicating that the results must be interpreted with caution.

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