PracticeUpdate: Haematology & Oncology | Vol 1.No.3 - 2016

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Robotic equals open surgery for prostate cancer Comment by Thomas Guzzo, MD, MPH T his is the first published randomised trial comparing outcomes between robotic and open prostatectomy for men with The robotic patients did have significantly less blood loss, a shorter length of stay, and were less likely to have had an intraoperative adverse event.

prostate cancer. The study included 308 men undergoing surgery at a single centre. The au- thors report no significant differences in short- term urinary and sexual function outcomes at 6 and 12 weeks. There was also no significant difference in positive margin rates between surgical approaches.

With the widespread adoption of robotic surgery in the United States over the last dec- ade, this trial is unlikely to have a significant impact on practice patterns. This study does potentially validate what we have already ob- served clinically: regardless of approach, pros- tatectomy functional and oncologic outcomes are equivalent and more dependent on surgeon expertise and experience than a machine. It also demonstrates the potential short-term the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (74.50 vs 71.10; P = 0.09) or 12 weeks post-surgery (83.80 vs 82.50; P = 0.48). Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatecto- my group at 6 weeks post-surgery (30.70 vs 32.70; P = 0.45) or 12 weeks post-surgery (35.00 vs 38.90; P = 0.18). Equivalence testing on the difference be- tween the proportion of positive surgical margins between the two groups (15 [10%] in the radical retropubic prostatectomy group vs 23 [15%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a Δ of 10%. However, a superiority test showed that the two proportions were not significantly different (P = 0.21). 14 patients (9%) in the radical retropubic prostatectomy group versus six (4%) in the robot- assisted laparoscopic prostatectomy group had postoperative complications (P = 0.052). 12 (8%) men receiving radical retropubic prostatectomy and three (2%) men receiving robot-assisted lapa- roscopic prostatectomy experienced intraoperative adverse events. INTERPRETATION These two techniques yield simi- lar functional outcomes at 12 weeks. Longer term follow-up is needed. In the interim, we encourage patients to choose an experienced surgeon they trust and with whom they have rapport, rather than a specific surgical approach. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study. Lancet 2016 Jul 26;[EPub Ahead of Print], JW Yaxley, GD Coughlin, SK Chambers, et al.

There is a significant methodologic flaw that limits our ability to draw definitive conclusions from this study.

Robot-assisted laparoscopic prostatectomy vs open radical retropubic prostatectomy The Lancet Take-home message

• This randomised, multicentre phase 3 trial compared clinical outcomes of open vs robot-assisted laparoscopic radical prostatectomy in 326 men with newly diagnosed early-stage prostate cancer. Urinary function and sexual function were similar at 12 weeks post resection. Positive surgical margin rates were also similar at 10% vs 15% in the open vs robot-assisted laparoscopic prostatectomy groups, respectively (P = 0.21). • Robot-assisted laparoscopic radical prostatectomy is associated with clinical outcomes similar to those achieved with open radical prostatectomy. Abstract

benefits of robotic surgery including less blood loss, less pain, and a shorter hospital stay. However, I would caution readers when interpreting these results that, in my opinion, there is a significant methodologic flaw that limits our ability to draw definitive conclusions from this study. As noted in the methods sec- tion, this study was performed by two surgeons (one robot and one open) and therefore has questionable generalisability to all urologists who perform prostate cancer surgery. Addition- ally, at the start of the trial, the robotic surgeon had only completed 200 robotic prostatecto- mies compared with the open surgeon who had 15 years’ post-fellowship experience and had already completed 1500 open prostatec- tomies. With all due respect to both surgeons, I am not sure that this was a fair comparison.

the biopsy and radical prostatectomy specimens. Primary outcomes were urinary function (urinary domain of EPIC) and sexual function (sexual domain of EPIC and IIEF) at 6 weeks, 12 weeks, and 24 months and oncological outcome (positive surgi- cal margin status and biochemical and imaging evidence of progression at 24 months). The trial was powered to assess health-related and domain- specific quality of life outcomes over 24 months. We report here the early outcomes at 6 weeks and 12 weeks. The per-protocol populations were included in the primary and safety analyses. FINDINGS Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to radical retropubic prosta- tectomy and 163 to robot-assisted laparoscopic prostatectomy. 18 withdrew (12 assigned to radi- cal retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group. 121 assigned to radical retropubic prostatectomy completed the 12 week questionnaire versus 131 assigned to robot-assisted laparoscopic prostatectomy. Urinary function scores did not differ significantly between

BACKGROUND The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology. We aimed to com- pare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks. METHOD In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, were able to read and speak English, had no previous history of head injury, dementia, or psychiatric illness or no other concurrent cancer, had an estimated life expectancy of 10 years or more, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women’s Hospital (Brisbane, QLD). Participants were ran- domly assigned (1:1) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy. Randomisation was computer gen- erated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patient’s condi- tion. Further, a masked central pathologist reviewed

Dr Guzzo is Assistant Professor of Urology in Surgery, University of Pennsylvania Perelman Center for Advanced Medicine.

JOURNAL SCAN Improved outcomes with early salvage radiotherapy inmen with detectable PSA after prostatectomy for prostate cancer Journal of Clinical Oncology Take-home message • Salvage radiotherapy outcomes were examined in 1106 men with detectable PSA after radical prostatectomy for prostate cancer. At a median follow-up of 8.9 years, tumour stage, Gleason score, and pre-salvage radiotherapy PSA correlated with overall survival, cumulative incidence for biochemical recurrence (BcR), distant metastases, and cause-specific mortality on multivariate analyses. The risks of BcR, distant metastases, and cause-specific and all-cause mortality were significantly increased with each doubling of pre-radiotherapy PSA. • Reductions in BcR, metastases, and mortality may be achieved by using salvage radiotherapy at lower PSA levels. The authors argue against prolonged monitoring of PSA levels that delays the start of salvage radiotherapy after prostatectomy. Abstract

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0.001), DM (HR, 1.32; P < 0.001), CSM (HR, 1.40; P < 0.001), and all-cause mortality (HR, 1.12; P = 0.02). Using a pre-SRT PSA cutoff ≤ 0.5 versus > 0.5 ng/mL, 5-year and 10-year cumulative incidences for BcR were 42% versus 56% and 60% versus 68% (P < 0.001), DM 7% versus 14% and 13% versus 25% (P < 0.001), CSM 1% versus 4% and 6% versus 13% (P < 0.001), and OS of 94% versus 92% and 83% versus 73% (P > 0.05). CONCLUSION SRT outcomes are in part affected by factors associated with prostatectomy findings but may be posi- tively affected by using SRT at lower PSA levels, including reductions in BcR, DM, CSM, and all-cause mortality. These findings argue against prolonged monitoring of detectable postprostatectomy PSA levels that delay initiation of SRT. Improved metastasis-free and survival outcomes with early salvage radiotherapy in men with detectable prostate-specific antigen after prostatectomy for prostate cancer. J Clin Oncol 2016 Aug 01;[Epub ahead of print], Stish BJ, Pisansky TM, Harmsen WS, et al.

PURPOSE To describe outcomes of salvage radiotherapy (SRT) for men with detectable prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer and identify as- sociations with outcomes. PATIENTS AND METHODS A total of 1,106 patients received SRT between January 1987 and July 2013, with median follow-up 8.9 years. Outcomes were estimated using Kaplan-Meier for overall survival (OS) and cumulative incidence for biochemical recurrence (BcR), distant metastases (DM), and cause-specific mortality (CSM). Variable associations with outcomes used Cox or Fine-Gray methods, as appropriate. Multiple variable analyses used backward selection with P < 0.05 for retention. RESULTS In multiple variable analyses, pathologic tumour stage, Gleason score, and pre-SRT PSA were associated with BcR, DM, CSM, and OS; androgen suppression and SRT doses > 68 Gy were associated with BcR; and age was associated with OS. Each pre-SRT PSA doubling increased significantly the relative risk of BcR (hazard ratio [HR], 1.30; P <

VOL. 1 • No. 3 • 2016