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Dec 20, 2018

Welcome to the ASCO Daily News Podcast. I'm Lauren Davis, and joining me today is Dr. Shailesh Shrikhande, who is the professor and head of cancer surgery and the chief of GI and HPB surgery. He also serves as the director of Tata Memorial Hospital in Mumbai, India. Dr. Shrikhande, welcome to the podcast.

Thank you so much. It's been a real pleasure to be here on this podcast.

Today we're talking about pancreatic cancer in India and the challenges of creating a surgical program to treat this cancer. Of the 18 million cancer diagnoses predicted worldwide in 2018, nearly half a million will be in pancreatic cancer. In India, the rates of pancreatic cancer are also on the rise. What do you attribute this increase to?

So I would like to answer this question in two parts. One is that pancreas cancer still remains an uncommon cancer in the Indian subcontinent as compared to the Western world or the Caucasian world and even the Far East. We do not really know the reasons as to why the incidence is quite low in the sense that in the United States the incidence is about 15 per 100,000, but in my country it's about 4.1 per 100,000. So it's about one third the incidence one sees in the United States.

Having said that, India is the second largest most populous country in the world. And we have clearly a large population with increasing awareness. So we have the urban population, and there is a 5% to 10% shift from the rural parts to the urban parts of India, and that's where we start to see this cancer more and more than ever before.

So a decade ago, we definitely saw much less number of cancers which were pancreas and [INAUDIBLE] cancers. Now we see them in large numbers. The reasons are twofold. I think one is increasing awareness and widespread availability of diagnostics. Actually, even in not just in the metropolitan cities, but in tier 1, tier 2, tier 3 cities, and even in the smaller towns, you have much better imaging across India.

As you know, India is a country which resides in different centuries at the same time. So this is not universally distributed across this country. But clearly, we are able to detect them more. So I think part of it is increased incidence, part of it is increased awareness and detection, and this is resulting in we perceiving an increased threat of pancreas cancer in our country.

The real reasons for this rise is I think modern world, urbanization, environmental factors, smoking and alcohol, which continues to be on the rise in a country like this. India is also the diabetes capital of the world. And we do not know which of these factors or an interplay of these factors are contributing to the gradual but definite increase in [INAUDIBLE] and pancreatic cancers in India.
What is the current surgical strategy for treating pancreatic cancer? And what new treatments do you envision for the future?

The current surgical strategy is something which actually hasn't changed, but has just got refined over the last three decades. This has happened worldwide. And India is also no exception, especially in centers like ours.

So complete radical removal of the cancer, the best of surgical techniques, is perhaps the only way to give the patient a chance of a complete cure. So the current surgical strategy is if the disease is localized, if the disease has not spread, is not metastatic, if the patient can withstand a supra major extensive resection, the best thing is to do a radical surgical operation and remove it. Some of these tumors in selected patients can be removed laparoscopically or by robotic means, while some of them will continue to receive conventional surgical approaches.

As regards new treatments, what has really changed over the last decade is the fact that it's no more just a domain of the surgeon to cure pancreas cancer. You need the medical oncologists. You need the radiation oncologists. You need the genetic specialists. You need the people who understand the molecular biology of the disease much better as we move in the era of precision medicine. And therefore, you are able to individualize the pancreatic cancer and perhaps offer them a whole battery of treatment, and it's not just surgery.


Having said that, surgery remains at the core. But as you would know that if I were to see 100 patients of pancreas cancer in my clinic, I'm able to offer surgery to about 30 or 40 of them, because 60 of them would present to us already at a stage where it has metastasized. It's not just localized to the pancreas, but it's spread elsewhere. So we need to look at not just the curable, resectable disease, but we also need to look at what are the other avenues of evolving chemotherapy, and so on and so forth.


What kind of program have you developed at your cancer center?
So what we have done is, it's been an ongoing journey. And it continues to be an ongoing journey even now. And in this particular situation, renal center where in the late '90s, in the early '90s to be precise, we already went into an organ-based vertical split in the department of surgery and medical oncology and radiation oncology. So way back in 1992, something which is revolutionary for a country like India, we had people who were specializing in gastrointestinal cancer surgery, and then we had people specializing in thoracic surgery, breast surgery, uro oncology, so on and so forth.


We still have a large number of surgeons in India who would be practicing surgical oncology, but this center made the change in 1992 to move on towards specialized mission. And now we are no more gastrointestinal surgeons. We are pancreas surgeons, liver surgeons, gastric cancer surgeons. So we've got further super specialized as far as development of surgery's concerned in this center.

But in the last decade, we've also moved on to the concept of a disease management group. So we have the gastrointestinal disease management group, wherein it's not just the surgeons, but the medical oncologists, radiation oncologists, pathologists, interventional radiologists, molecular biologists, nuclear medicine specialists, all of them are specialized and focused only on to gastrointestinal cancers, thoracic cancers, uro-oncology cancers, thymic cancers, so on and so forth.


So one of the programs that we have developed is to focus and develop complex organ surgery, like pancreas surgery, G2 extended gastrectomies as well as liver surgery, to speak for my speciality. And this has happened over a period of time.

So just to give you an idea, when I started way back in 2002, at that point in time, we were doing about 25 Whipple resections a year, which is removal of the pancreas head. This would mean that we were doing about two of these operations or three of these operations in a month, and we would average somewhere between 30 to 35, at best, pancreas resections in 2002 when I was just joining [INAUDIBLE] the staff.


18 years down the line, we are already doing about 200 of these resections a year. So we are clearly a high volume center. But this has not happened overnight. It happens because of a sustained focus in developing that. Then the administration is also looking at the kind of perioperative outcomes and the transfer and documentation that we have. We have prospective databases, which establish the fact that we are a center of excellence. But it's not just the surgeon. It's also the paramedical staff, the intensive care, the intraoperative assistance from the OR nurses and other people, as well as the pain clinic, the anesthesia is now specialized. All this has developed over a period of time.


The residency program has also evolved. So in 2010, we became the center for training surgical oncologists for the whole country. We've been traditionally doing this, but now we have a specialized residency program. So nearly 55% of the cancer surgeons and the oncology skilled workforce in this country undergoes training at the Tata Memorial Center, which is India's largest cancer center.
Just to give you an idea, we have seen 73,000 new patients of cancer last year in oncology. So this kind of workload has resulted in the gastrointestinal and HPB surgical service to not just double, but triple the number of registrations and the number of patients coming in to seek treatment from us. And this is the kind of program that is ongoing, and it has developed to a stage where we are able to document this work and attract more work [INAUDIBLE].


That's great. And what have been some of the challenges in creating such a program?


So I'll tell you one thing, as I did mention earlier, that India lives in different centuries at the same time. So we have islands of excellence, no doubt, but it's not that training and education is standardized across this country. So you will have institutions and you will have programs which are very well designed for young doctors, and they will develop well over a period of time.
But as you would know, multidisciplinary care does not mean only clinicians. It does not mean only a surgeon. It does not mean a medical oncologist and a radiation oncologist, and they complete the entire comprehensive oncology management of a patient, not at all. So we need to improve in areas where it comes to nursing, where it comes to intraoperative nursing, where it comes to diagnostics.


So all of these things, which I, today, in 2018, take it for granted, was not something which was very well established when I joined on the staff in November 2002 as an assistant professor. At that point in time, one had to align the other people around into believing that excellence is something which happens with a lot of people working together, so that you can achieve an uncommon goal.


First of all, it's difficult for them to see what goal we are talking about or what destination I am trying to take them to. And the second is to keep them motivated and make them enjoy the process. It can be just a dreadful job, but something which you can pursue with a lot of passion, and infuse that kind of enthusiasm and passion and motivation, so that the others also kind of come together. And then teams are the things that matters the most, if you ask me.


So these were the challenges when it came to convincing people. And at that time, initially, you don't have too many people who go with you. But once you start doing all the work yourself-- and you may be leading the particular program, but actually one needs to work the hardest yourself. And then when you start seeing the results coming, and the others are also getting motivated and joining you.


So these were clearly huge challenges in the beginning for the first three to four to five years. But each year, we started documenting our work, we started publishing our work. And once you start doing that, people notice it. So good work or good news takes time to spread. Bad news spreads very fast. But good news takes a little while. But this has taken a while. And then our statistics and data clearly show the kind of increasing work and recognition that we have got in the past decade.


Do I have challenges now? We clearly have challenges, because we have the advent of laparoscopic and robotic surgery. We have the robot with us. But the next round of challenge is, this is a complex surgery, where people need to be trained first in conventional surgery. If they do this complex surgery well in the conventional fashion, then they need to make the transition to laparoscopic or minimal access or robotic training.


Then we also need to factor in increasing costs, which are very relevant to a country like India. Not just in India, even in the United States this is important. And these are other challenges for me to make this program not only sustainable, but also grow.
The next challenge I have is I have so many patients. We are a country of 1.2 billion. And the number of reference are such that perhaps this center has the potential to do about 300 to 350 resections, but we are today able to do only 200 simply because I have a logistics problem. I have a manpower problem. I have a limitation for the number of ORs that I can utilize in a week.
When I started out, I had six ORs a week. Today my overall gastrointestinal team has 15 ORs a week. And we have six ORs only for pancreas and gastric surgery. And even then, I have an embarrassing wait list of about eight weeks. This eight weeks may not be a lot if you compare with some health systems like the UK and Canada. But when a patient gets a cancer and [INAUDIBLE] to an aggressive cancer like a pancreas cancer, people, if they are fit enough to undergo surgery, would want the surgery to be done not tomorrow, but yesterday.


So these are challenges for us in trying to expand this program and make it better. But certainly our experience in the last decade encourages me to be confident that we will be able to expand it more and more in the next few years.


So I'm curious, what are your measures of success in treating patients with resectable pancreatic cancer?


So it's very clear. These are the standard internationally accepted to specific areas. And the measures would be the perioperative outcomes for resectable disease. How good is the quality and completeness of surgery, which is dependent on surgical training, surgical experience, surgical volume, as well as hospital volume. And beyond that, it's also about the quantity of pathology that you have with you, and the quality of medical oncology, and the kind of chemotherapy and radiation therapy that we offer.


So immediate outcome is the perioperative outcomes. And when I say perioperative, it's not just the 30-day mortality. It's the 90-day mortality that one should look at. And one should look at the standard outcome measures for morbidity based on something like the [INAUDIBLE] classification for grades of complication. So if you're able to objectively look at every month's audit, how well you are doing for complex surgery when we treat them with surgery for resectable disease.


But the real measure of success as an oncologist and as a doctor who's aiming for a cure in a very aggressive cancer is also the long-term outcomes. But unless you have good short-term outcomes, you can't even hope to have a good long-term outcomes.
So have we done very well in terms of short-term outcomes? Yes. Our results are comparable with the very best in the world. Any center worth their mention, we would be able to feel satisfied that we do as well as it's done, say, in America, Japan, Germany, wherever you have these centers of excellence.


Now, the long-term outcomes is also much dependent on human biology. But if the patients do not have morbidity and very low mortality rates, these are the very patients who are going to get post-operative chemotherapy as well. If you develop too many complications, then they take time to recuperate, and then the time to start in chemotherapy also gets delayed. So surgery remains the backbone. But in addition to that, chemotherapy has improved the outcomes of pancreas cancer. So we want the patient to go on to chemotherapy soon after.


And then the measure, of course, is after good complete radical surgery and complete high-quality chemotherapy, how long are the patients living? So I would divide the long-term measure into periampullary tumors, which we tend to see in large numbers in my country, and the classical pancreas cancer or the pancreas ductal adenocarcinoma.


Our five-year survival rates would be about 20% to 25% for pancreas ductal adenocarcinoma after complete resection. This happens because the vast majority of tumors that we would resect would have disease which is not just localized to the pancreas, but it's already spread to the lymph nodes by the time we operate on them. The small percentage of patients in whom the disease does not go to the lymph nodes, you will have about 40% to 60% of them who are alive at five years, if not longer.


The periampullary tumors are actually the better tumors who offer the more complex operation. But there we can hope for success rates of 40% to 60% at the end of five years, even with lymph node-positive disease. So these would be my measures of long-term success in addition to measures of short-term success, which is based on perioperative outcomes.


And it sounds like you touched on my next question a little bit, where I'm wondering if these procedures increase progression-free survival or lead to cure rates.


Yes. So I think I partly did address your question. The fact is that if you leave disease behind and you do incomplete surgery, you are definitely compromising your so-called PFS or progression-free survival. Progression-free survival should be a good terminology to use provided you have completely removed the tumor in the first place.


I know that pancreas cancer is considered to be a systemic disease, and it indeed is one. I also know that you can have circulating tumor cells in the blood, which as yet are not easily detectable with any of the modern diagnostics.

So I know that a number of patients which we operate, thinking that they are resectable disease, may, in fact, be having sleeper cells elsewhere which get activated soon after surgery or any form of treatment. And these patients might fail early. But it's not the fault of surgery that they fail early. It's just that the disease is more aggressive in these patients. But in those patients in whom the disease is truly localized, a well-done operation will certainly ensure that you get a long progression-free survival.

And as I maintained before, you can try and give only chemotherapy or radiotherapy or targeted therapy or immunotherapy and not offer surgery, you will not get patients who are getting cured. You might get a degree of control. You might get a degree of downsizing. Patients will feel well for a period of time. But the chance of a cure is lost.


So I say this not because I am a surgeon, but because that's where the objective evidence-based data is available for a large number of years. This is not data based on the last one decade. It's about three to four decades that we have good data that if you can completely do these radical procedures in well-selected patients-- and to remind you, these are only three or four patients out of 10. We are operating only on three or four, not all of them. But in these patients, if you do a good operation, you will certainly give them a chance of cure or a longer progression- or disease-free survival.
Very informative. Again, today my guest has been Dr. Shailesh Shrikhande. Thank you so much for being on our podcast today.


Thank you so much.


And to our listeners, thank you for tuning in to the ASCO Daily News Podcast.