Optimal Surgical Approaches in Cystectomy - Piyush Agarwal

July 22, 2019

Piyush Agarwal reflects on a debate at the EAU 2019 where he debated Seth Lerner, MD who is a preeminent urologist in bladder cancer.  Dr. Lerner was favoring open surgery and Dr. Agarwal was favoring robotic surgery for the purpose of the debate as he conveys the positioning of the arguments with Charles Ryan.  If you look at the robotic literature in urologic cancers, there is no evidence of any oncologic inferiority of prostate cancer surgery done with a robotic approach. Recently in bladder cancer, the RAZOR trial was completed, and that also showed that they were not oncologically worse than open surgery.  In the RAZOR trial, there was a two-year end-point for progression-free survival. Outcomes of recent trials are discussed and perhaps differences in outcomes and techniques in male patients versus female patients.  


Piyush Agarwal, MD is Head of the Bladder Cancer Section in the Urologic Oncology Branch. He specializes in the multidisciplinary management of urothelial cancer and complex surgical techniques including robotic cystectomy and continent urinary diversions. He is also an expert in other urologic cancers including prostate, testicular, and penile carcinoma. His clinical and laboratory research focus on all aspects of bladder cancer, specifically, Bacillus Calmette-Guerin (BCG)-refractory disease and molecular targeted therapy.

Charles J. Ryan, MD, the President and Chief Executive Officer of The Prostate Cancer Foundation (PCF), the world’s leading philanthropic organization dedicated to funding life-saving prostate cancer research. Charles J. Ryan is an internationally recognized genitourinary (GU) oncologist with expertise in the biology and treatment of advanced prostate cancer. Dr. Ryan joined the PCF from the University of Minnesota, Minneapolis, where he served as Director of the Hematology, Oncology, and Transplantation Division in the Department of Medicine. He also served as Associate Director for Clinical Research in the Masonic Cancer Center and held the B.J. Kennedy Chair in Clinical Medical Oncology.

Read the Full Video Transcript

Charles Ryan: Hello, I'm delighted to be joined today by Dr. Piyush Agarwal, who is Head of the Bladder Cancer Section of the Urologic Oncology Branch at the National Cancer Institute in Bethesda. Thank you for joining us today.

Piyush Agarwal: Thanks for having me.

Charles Ryan: We're going to talk about bladder cancer. We're here at the EAU in Barcelona where I understand you had a debate about optimal surgical approaches to bladder cancer. Tell us about that story. 

Piyush Agarwal: Yes. Right now, there is a lot of controversy going around robotic approaches to cancer operations. New England Journal recently published an article that was a randomized trial of 33 centers looking at radical hysterectomy for cervical cancer done in an open approach versus a minimally invasive or robotic approach. The conclusion of that trial was that the four-and-a-half-year disease-free survival was worse in the robotic minimally invasive group. As a result, it was deemed to be oncologically inferior. 

The FDA actually has now issued a warning that anybody doing any robotics for cancer operations needs to show outcomes beyond 30 days in terms of cancer control that are reasonable. It's a very reasonable recommendation. I think a lot of people who favor open surgery are extrapolating those results to robotic surgery.

If you look at the robotic literature in urologic cancers, there is no evidence of any oncologic inferiority of prostate cancer surgery done with a robotic approach. Recently in bladder cancer, the RAZOR trial was completed, and that also showed that there was not oncologically worse than open surgery.

Charles Ryan: Over what period of time?

Piyush Agarwal: In the RAZOR trial, it was a two-year end-point for progression-free survival. They estimated up to a 15% difference. If there was a 15% worse disease-free survival, they would still think that it was not oncologically inferior. It turned out that they were almost identical, so there was really no difference. We launched into a debate, and I debated Seth Lerner who is arguably one of our preeminent urologists in our specialty. He was favoring open surgery and I was favoring robotic surgery. 

Frankly, I think at the end of the day it comes down to what the surgeon is comfortable doing. It's my personal belief and I've been privileged to have been trained in both that a surgeon should be able to do both approaches. In 2019, I just feel like robotics is here, and if you can do it and do it for the right patient, then I think it just gives you another tool set. 

Charles Ryan: Let me ask you a couple of questions. Let me approach this as two potential myths about robotic surgery that I think we should address. Myth number one is it a myth or not, that the lymph node dissection is not as adequate when laparoscopic surgeries are done versus open. Myth number two is that the pressure used, the C02 I guess it is to insufflate is potentially associated with enhancing tumor spread. Can you address those two questions? 

Piyush Agarwal: Yes. I would say that number one, the lymph node yield, it's a myth because both in the RAZOR trial and then in several other randomized trials, the lymph node yield has been almost equivalent between open and robotic. Again, I think in the early days of robotic surgery when people were unable to ... Their times were long and they're trying to keep the time short, they kind of skimped on the lymph node dissection, but I think now with people having more expertise, they are realizing what they're really capable of doing. 

Frankly, I do both surgeries and I just feel like I can clean out the pelvis a lot better with the robotic approach because I'm magnified tremendously than when I am doing open surgery. Having said that though, I think you can do a good lymph node dissection with either approach. At least the published data in randomize efforts, we showed that the lymph node yield is comparable.

In terms of the pneumoperitoneum, so that was one of the issues in this New England Journal article that I mentioned, that there were more recurrences in the hysterectomy robotic or minimally invasive group. And so they worried the pneumoperitoneum is a potential source. Well, we haven't seen that in prostate cancer, and in bladder cancer, there were some early reports of some weird recurrences that we don't typically see with open. Some bowel recurrences, some pelvic recurrences, and some port site recurrences.

I frankly, as I've evolved over time doing robotic surgery, I realized very early that if you don't bag your lymph nodes and you don't bag the bladder properly, and you're not closing off different parts of the bladder as you disconnect it, that you do increase the risk of those type of local recurrences. I think you have to adhere to good oncologic principles.

I'm not sure it's necessarily the pneumoperitoneum, I think it's improper handling of tissues that might be affected with cancer in the setting of the pneumoperitoneum. If you bag your specimens before you remove them, I haven't seen any of those weird patterns recurrences. The randomized trials and some of the data that I presented in the talk also suggests that there wasn't any increase, except for one trial by Bernie Bochner that showed some differences in the recurrences. 

The other four randomized trials are not showing a difference with weird recurrences. The RAZOR trial which was the largest trial, which was a multicenter trial, probably is the best evidence of no weird recurrences unique to robotic surgery.

Charles Ryan: Is that a settled issue you think? 

Piyush Agarwal: I don't know if it's settled, I think everybody's going to have that concern. I certainly think that pneumoperitoneum with improper handling of the tissues could be a problem. I think that may have contributed in this hysterectomy trial because they also use a device called a uterine manipulator. That is a device that can lead to perforations and lacerations of the uterus. If you have a tumor-filled organ and you're manipulating it, and now you have some spillage of tumor microscopically with pneumoperitoneum.

We don't use such a device in bladder cancer when we do the operation, and as long as we bag all of our specimens, I mean I don't think that the pneumoperitoneum- 

Charles Ryan: I was wondering about a T2 for example, where you might be worried that even if you don't properly bag the bladder that would be a ...

Piyush Agarwal: It'll be right there on the surface. To that point, in the RAZOR trial, again, these are mostly muscle invasive tumors where they weren't that aggressive. They didn't see an increased local recurrence rate in the robotic group for those more aggressive tumors. Having said that, there were some original publications, I was a co-author on one of them, that showed a slightly higher positive margin rate with a robotic approach in more aggressive T3, T4 tumors. 

Everybody's got to make their own decision. I, as a surgeon who do both, I favor open surgery for T3, T4 disease. Not that I don't think you could do it robotically and do it safely, I just think that those are the types of tumors where sometimes I just need to feel how firm the tumor is and just go widely, and I think that extra help me. Having said that, there are several expert robotic surgeons who can do those operations safely and not get positive margins. 

Charles Ryan: I see. Final couple of points. One is urinary diversion. How is it typically done when you're doing the laparoscopic approaches, the robotic approaches? Does it differ from the open? What's the story there? 

Piyush Agarwal: One of the criticisms that I've heard at this conference from a lot of the open surgeons is that robotics is great but everybody's doing the diversion extracorporeally, and so you're making an incision to do the diversion. They are saying, in addition, they're doing, conduits when they do it intracorporeally because it's easier to do a conduit than it is to do a neobladder. If you look at the data from, again, the RAZOR trial, they were actually slightly more continent urinary diversions than incontinent or conduits done in the robotic groups. The robotic group actually did more continent diversions.

Charles Ryan: Neobladders?

Piyush Agarwal: Yes, neobladders, and then there was one patient who had a continent cutaneous pouch. I think a lot of early robotic surgeons are doing everything extracorporeally to get more comfortable with it. There's a new trial in the UK called the iROC trial that's going to compare extracorporeal to intracorporeal urinary diversion. Both groups will have robotic surgery done for the removal of the bladder and the lymph nodes, but then the reconstruction will be extracorporeal versus intracorporeal. 

All the published results that I mentioned from a recent meta-analysis of the five trials in robotic versus open were all extracorporeal diversions. Complication rates are not different because most of the complications are from the reconstruction. If you do it open in both groups, you're going to see no real difference. It will be interesting to see with intracorporeal if the complication rate can be lowered. If it can, then that may have an argument favoring a completely robotic approach. 

Charles Ryan: Got it. The final question I have is, you've talked a lot about uterine cancer, cervical cancer approaches. Are there differences in the approach between men and women around these two open versus robotic?

Piyush Agarwal: Yes. In women, robotic surgery can be done just as easily as it's done in men. There is a potential even with robotics to do more organ sparing cystectomy. We are now realizing as a specialty that we do a pretty morbid operation for bladder cancer, and if we can reduce some morbidity, improve the quality of life. Some of those approaches entail prostate preservation in a well-selected candidate and vaginal wall sparing in well-selected female candidates. 

These are potentials, I can just say that unfortunately, a lot of people don't have a lot of experience with women because the tumor just doesn't affect women as often, but you can easily do robotic approach in women as in men. 

Charles Ryan: Great. Well, I think you've answered all my questions, so that must be anything we need to know, right? 

Piyush Agarwal: Yes.

Charles Ryan: Thank you so much for joining. It's really fascinating topic and conversation, I really enjoyed it. 

Piyush Agarwal: Great. Thanks, Chuck, appreciate it.