At 24 months’ follow-up, the only phase 3 randomized clinical trial to directly compare functional and oncologic outcomes between robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy shows no evidence for a clear advantage of one approach over the other, say researchers.
The new results at 24 months’ follow-up were published online July 12 in the Lancet Oncology.
As previously reported by Medscape Medical News, the trial’s 3-month follow-up results, published in 2016, showed no significant differences in functional and oncologic outcomes between the two approaches.
The current study shows that functional and sexual outcomes for both approaches have remained comparable at 6, 12, and 24 months’ follow-up.
However, the oncologic outcomes “require ongoing follow-up and further investigation,” the authors say.
The study also showed that 1 of 5 patients continued to experience high levels of psychological distress, regardless of surgical approach.
“Robot-assisted laparoscopic prostatectomy has been widely adopted as the preferred surgical technique for radical prostatectomy without previous validation of improved outcomes,” Franklin and colleagues write. “Our study showed that this technique can obtain equivalent functional outcomes to open surgery, with a decreased risk of biochemical recurrence during 24-month follow-up.”
The researchers “advise caution in interpreting the oncological outcomes of our study because of the absence of standardization in postoperative management between the two trial groups and the use of additional cancer treatments.”
“[A]lthough our results might have implications for long-term patient outcomes, further validation is needed,” they comment. “Clinicians and patients should view the benefits of a robotic approach as being largely related to its minimally invasive nature.”
Gardiner also pointed out that “relying on PSA [prostate-specific antigen] at 24 months without fully taking into account patients who had undergone treatments known to lower PSA values could be misleading ultimately in terms of cancer outcomes.”
The researchers “will continue to monitor these patient groups to ascertain if there is a better oncological outcome for one procedure compared with the other,” Gardiner told Medscape Medical News. “In the absence of evidence for a clear advantage for one approach over the other at 24 months, the need to embrace robotic prostatectomies when cost is a critical issue, for example in Third World countries, should be questioned,” he added.
In an accompanying editorial, Vidit Sharma, MD, and R. Jeffrey Karnes, MD, both from the Department of Urology at the Mayo Clinic in Rochester, Minnesota, agree that “the oncological data remains preliminary and should not be accorded too much weight. The gold standard for prostate cancer surgery remains a high quality radical prostatectomy, regardless of the approach.”
This trial “remains a comparison of one robotic surgeon’s outcomes to another open surgeon’s outcomes,” they say. “[T]he overall narrative of criticism against the trial can be distilled down to concerns regarding the lack of generalizability of both the open and robotic surgeries undertaken.”
The editorialists say that the fact that more of patients who underwent open surgery experienced biochemical recurrence than those who underwent robot-assisted laparoscopy is “the most controversial finding from this report.” They note that the treatment groups “were balanced for high-risk disease but skewed.” Eight patients in the robotic prostatectomy group had grade 9 Gleason scores compared to 14 patients in the open surgery group, they point out.
Sharma and Karnes also agree that the trial “has implications for emerging markets, such as parts of Asia, South America, and Africa, where it is crucial to consider the substantial investment necessary to sustain a robotic arms race.”
They suggest that investment could be made in surgical training and skills assessment instead, and add that the trial “should encourage medical professionals to clearly define the benefit of novel technologies before promoting their widespread adoption.” They emphasize that the study‘s oncologic results “should be viewed with caution” and that investing in robotic technology should be questioned in developing nations when cost is a critical issue.
For the study, 326 men aged 35 to 70 years who had been newly diagnosed with localized prostate cancer were enrolled between August 23, 2010, and November 25, 2014. A total of 151 were randomly assigned to undergo open surgery, and 157 were assigned to the robotic procedure.
The study showed that there were no significant differences in mean urinary and sexual function scores between the two procedures at 6, 12, and 24 months. Expanded Prostate Cancer Index Composite scores continued to be nearly identical for the two procedures for urinary continence (91.33 vs 90.86; for both, P < .0001), as were sexual function scores on the International Index of Erectile Function Questionnaire (33.95, P = .0003; vs 33.89, P = .0004).
However, biochemical recurrence occurred in 13 patients in the open surgery group compared to four in the robotic surgery group (P = .0199), even though more men in the robotic surgery group had positive margins (15% vs 10%; P = .21). Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher.
“The finding that there was lower biochemical recurrence in the robot-assisted laparoscopic prostatectomy group is surprising given that more men in the robot-assisted group had positive surgical margins,” the researchers say. “A potential hypothesis for these conflicting outcomes is that artefactual positive margins could be created during robot-assisted prostatectomy because of trauma from robot-assisted or laparoscopic instrument handling, or specimen extraction through a small incision. This hypothesis requires further investigation.”
Interestingly, imaging evidence of progression was not significantly different between the two groups: three men in the open surgery group compared to one in the robotic surgery group. Also, for nine men in the open surgery group, the postoperative PSA level was greater than 0.2 ng/mL.
Scores for psychological distress at 24 months were high for patients in both groups: 29 (21%) men in the open surgery group and 28 (22%) in the robotic surgery group. “This was a surprising and important finding,” said Gardiner.
Suzanne K. Chambers, PhD, director of the Menzies Health Institute Queensland at Griffith University, who was one of the study‘s chief investigators, is currently looking at ways to address this.
In a statement issued by Cancer Council Queensland, Chambers said that “issues such as sexual dysfunction, urinary and bowel changes, and even fear of recurrence can all lead to elevated psychological distress.”
Although there were no significant differences between the groups in terms of physical and mental quality of life, bowel function, cancer-specific distress, psychological distress, urinary symptoms, and vitality, these findings “highlight the need for improved distress screening and psychological care long after treatment ends,” said Chambers. “For optimal prostate care, there needs to be evidence-based psychological intervention that is responsive to masculinity and related concerns.”
When approached for comment, Gerald Chodak, MD, a urologist in Highland Beach, Florida, who is a regular video contributor to Medscape Urology, said that until such time that one procedure proves definitively better than the other, the focus should be on surgical skill, not the surgical approach.
“Whether it is an open or robotic-assisted approach, radical prostatectomy needs to be performed by someone who does at least 50 procedures a year, and who keeps tabs on the oncologic outcomes and postoperative urinary and sexual function,” he said in an interview.
Patients should be encouraged to ask prospective surgeons how many radical prostatectomies they perform annually, said Chodak. “The surgeon who does 20 a year is performing one procedure every 2 to 3 weeks,” he explained. “That’s not enough to become expert.”
Similarly, if a physician has not tabulated his or her results, “keep looking,” Chodak advised.
The study was funded by Cancer Council Queensland. Dr Chambers and coauthors have disclosed no relevant financial relationships. Dr Chodak has financial relationships with Amgen Inc, Dendreon Corporation, Johnson & Johnson Pharmaceutical Research & Development, LLC, Medivation, Inc, Myriad, and Watson Pharmaceuticals, Inc.