Treatment Approach: Case Study in Aggressiveness Metastatic Urothelial Carcinoma - Makarand Khochikar

August 10, 2020

Makarand Khochikar, President of the Urological society of India –West zone and Chairman of the Department of Uro-oncology at Siddhi Vinayak Ganapati Cancer Hospital in Miraj, joins Ashish Kamat, MD to discuss the case of a 70-year-old patient who presented with left-side loin pain and intermittent hematuria. An ultrasound and CT scan revealed a solid-lesion in the left kidney, lesions in the left lateral wall of the bladder, and multiple kidney stones. Dr. Kamat notes that given these symptoms, further diagnostic testing — including cystoscopy and transurethral resection of bladder tumor (TURBT) — would be necessary to determine the histology of the presented tumors. Following these tests, the patient was diagnosed with urothelial carcinoma as well as clear cell renal cell carcinoma, and later, carcinoma in situ (CIS) and muscle-invasive disease was discovered in the bladder. Given this combination, Dr. Khochikar and Dr. Kamat consider the proper treatment approach, which included a radical cystoprostatectomy. 

Biographies:

Makarand Khochikar, MS DNB, Dip Urol, FRCS, FEBU, National delegate for the Indian section of SIU, President of the Urological Society of India –West zone, Chairman of the Department of Uro-oncology at Siddhi Vinayak Ganapati Cancer Hospital, Miraj, India and is also a member of the management committee and Governing council of the hospital.

Ashish Kamat, MD, MBBS, President, International Bladder Cancer Group (IBCG), Professor of Urology & Cancer Research, MD Anderson Cancer Center, Houston, Texas


Read the Full Video Transcript

Ashish Kamat: Welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat. I'm a Professor of Urologic Oncology at MD Anderson Cancer Center in Houston, Texas, and it gives me great pleasure to welcome today Dr. Makarand Khochikar, who is Chief Urologic Oncologist at the Siddhi Vinayak Ganapati Cancer Hospital in Miraj. He's also the past President of the Urologic Society of India - West Zone. And more than just that, he is a good friend and a true expert when it comes to urology and uro-oncology in general. He has a huge case file that he has collected over the years that have some pearls as far as educational value when it comes to bladder cancer, and I'm really pleased to have him join us today for this session. Dr. Khochikar, please take it away.

Makarand Khochikar: Thank you, Ashish. It's been a great pleasure to be part of this UroToday symposium. This was a 70-year old gentleman who's hypertensive, was a chronic smoker for the last 40 years. He presented with left-sided loin pain, intermittent hematuria of six months. His ultrasound scan showed left-sided hydronephrosis, thinned out cortex, and there was a suggestion that the patient would have a solid lesion in the lower pole of the left kidney. And there were two large calculi in the upper ureter on the left-hand side. For all practical reasons, it looked like possibly a nonfunctioning kidney on the left-hand side. The bladder was thickened. There was no growth actually seen on the bladder ultrasound scan. His cytology was negative. His routine laboratory investigations were normal.

I'm just going to run through the CT scan and I'm sure you will agree the right kidney looks normal. There is a fair amount of hydronephrosis on the left-hand side. And there you are. You could see a solid lesion somewhere in the kidney on the left-hand side, somewhere in the middle lobe, and you can appreciate the right kidney is entirely normal.

So the gross hydronephrosis, a solid-looking lesion in the mid-pole, and this was reported on ultrasound as a thickened bladder. But when we look at here, this was all thickened wall. And these were areas I was worried about, whether patient has un upper lesion into the bladder itself. Now he has a gross kyphoscoliosis, an elderly man. The right side of kidney normal, gross hydronephrosis, and a solid-looking area here. The rest of the ureter, the upper ureter was dilated. And this is, I think is self-explanatory. You can see the beautiful right kidney here. The ureter is dilated and tortuous but no obstruction and no mass here. Couple of [inaudible] defects in the bladder. That's the stone here, that's the stone here. That's the stone, and this is a dilated upper ureter. So three stones, a solid-looking lesion in the left kidney, gross hydronephrosis, no function in that kidney, and a couple of lesions in the left lateral wall of the bladder.

This is standard, a simple KUB just to tell you that the stones are, and the kyphoscoliosis here. So Dr. Kamat, could I just ask your opinion, and what would be a diagnosis? The guy who's smoker, hematuria, solid mass with hydronephrosis with the stones, and sort of a point filling defect in the bladder. What do you think about this case?

Ashish Kamat: So in these situations, obviously, the bladder lends itself to a quick cystoscopy and visualizing the tumor to confirm what it looks like on the CT scan, which is likely a true bladder cancer. The stones are obviously causing obstruction. You did not say that the patient was sick. So I wouldn't think of nephritis or anything along those lines, but the lesion looks solid enough in the kidney that I would be suspicious either that this is an upper tract urothelial carcinoma that has an atypical presentation, or it actually is a garden variety kidney cancer that just happens to coexist in someone that you're also suspecting a potential bladder tumor.

So this could be the same histology or different histologies in the patient. And I would actually do further workup in this patient, in the form of a cystoscopy and TURBT. And if it were a bladder cancer in the bladder, then if it was invasive, I would move along the path of doing a cystectomy and then take out the kidney at the same time. If it was noninvasive in the bladder, then I would want to address the kidney to see if it's urothelial or if it's a kidney cancer of renal origin.

Makarand Khochikar: Yeah, absolutely perfect. Do you think at one point, is there a possibility of squamous cell carcinoma? A nonfunctioning left kidney, stones in that kidney. He was not sick or he did not have any infection or sepsis, but that solid-looking lesion, could it be a squamous differentiation of urothelial carcinoma or a squamous cell carcinoma itself?

Ashish Kamat: You raise an interesting point that chronic irritation can cause squamous cell de-differentiation in tumors, but in general, they don't tend to have as solid an appearance as is noted on the imaging. Now clearly it's a possibility, but I wouldn't have put that higher in my differential. That's not to say it couldn't be the case.

Makarand Khochikar: Yeah, perfect. So I'm just going to run through this cystoscopy and the urethra looks normal. Just a quick cystoscopy and there are a lot of papillary tumors right from the prostatic urethra, and multiple tumors we saw. Initially, I thought they were small papillary tumors, but in contrary to what we saw on a CT scan, see there's one lesion, another lesion, just almost everywhere. So it was something like pan-urothelial multi-focal lesions, almost sprayed out or fanned out in the entire bladder, the bladder was trabeculated. And a significant number of lesions within the prostatic urethra, as well as the bladder itself. So as we discussed, this could be urothelial carcinoma of the bladder with urothelial carcinoma of the upper tract or urothelial carcinoma in the bladder with squamous cell carcinoma in the kidney.

So as Dr. Kamat has pointed out, we did a TURBT and a left nephroureterectomy with the pelvic lymph node dissection, because that was on our mind, probably one pathology itself. As Dr. Kamat said, this could be a different histology, but the treatment would not have changed. So initially, TURBT we did, and we were planning to do a left nephroureterectomy. And this was post-TURBT, we did a nephroureterectomy, a grossly thinned out kidney with the stones here, what you can see in the upper ureter. And grossly thinned out kidney and a solid-looking tumor here. This was the picture taken by the pathologist, here's much, much bigger stones here, dilated upper ureter. And this solid-looking lesion mainly coming from the thinned out cortex rather than coming from the pelvicalyceal system.

When we got the histology, we were surprised. This is a urothelial carcinoma of the bladder, pTaG3, that was quite obvious here. And the histology from the left kidney was clear cell RCC, it was pT3N0, all the lymph nodes were clear. Now, Dr. Kamat, you got it right in the first guess looking at the solid lesion. So what do you think would be the best approach now? Now the kidney is out, the lymph nodes have been taken care of. We've done a TURBT, I think it was a fairly good TURBT, including the prostatic urethral biopsies. So what should be the next step?

Ashish Kamat: So Dr. Khochikar, at this point I would discuss with the patient, the pros and cons of adjuvant therapy for renal cell carcinoma, and as you and our audience know, there's no clear evidence that adjuvant therapy actually helps these patients. So observation would be perfectly fine unless you have a clinical trial that you could offer him, per se. As far as the bladder tumor is concerned, it looks like you resected the tumor and you have a high-grade Ta diagnosis. But on your cystoscopy, you did mention that on the way into the bladder in the prostatic urethra, there were some tumors as well. So I would actually counsel the patient on a repeat cystoscopy to see if there's anything in the prostatic urethra, resect and/or find that and/or do a complete TURBT in the bladder, just in case. And I'm not saying you didn't do this, but just in case you were thinking that this was invasive and you didn't do a deep resection, I would go ahead and clarify the bladder situation before making treatment recommendations between bladder conservation or non-conservative therapy.

Makarand Khochikar: Yeah, we did resect the tumors in the prostatic urethra. They were also sort of Ta, a high-grade disease. Prostatic stroma, there was no invasion in the prostatic stroma. So ultimately, all the regions in the bladder and the prostatic urethra were Ta and high-grade. So we actually planned on doing the check cystoscopy for a restaging in about six weeks' time. And when we went back in six weeks' time, we found that the bladder is still studded with multi-focal, multiple tumors. Now I'm just thinking, looking at the extent of the disease itself, any sort of intravesical therapy is probably going to delay the inevitable. So I've just recommended him a radical cystectomy with a urinary diversion, probably an ileal conduit in the solitary kidney and ureter. I'm sure you will concur with me, or you have a different opinion on this?

Ashish Kamat: No, that's a very reasonable treatment option for the patient. If the patient was motivated and wanted to really try everything to save the bladder, then a trial of intravesical immunotherapy with BCG is also a very reasonable option. Patients with prostatic urethral tumors do respond, so long as, like you said, you've clarified that it's not invasive and it's not into the stroma, et cetera, but both are reasonable options. And sometimes, it really depends upon the socioeconomic status of the patient. Can they afford to keep coming for multiple treatments and visits, or would they like one definitive therapy? So these are difficult situations that we have to discuss with our patients based on other factors other than cancer itself. And that's why I really truly appreciate the points that you raised today. Could I ask how far out the patient is now, and how well he or she is doing? Well, he in this case.

Makarand Khochikar: Yeah. He's doing extremely well. We did a radical cysto-prostato-urethrectomy and sort of an ileal conduit with the single ureter. So final histology actually showed carcinoma in situ at many places into the bladder, and at one point there was a muscle invasion also. So that was within six weeks of the first TURBT. So we could understand the aggressiveness of the disease. It's nearly three months since he had his cystectomy, all the lymph nodes were very clear, renal function is stable, and he's okay at the moment.

Ashish Kamat: And one follow-up question, and more for the education of our audience and viewers, what was the reason the patient, if he was thinking of a cystectomy in the first place, did not want to have the cystectomy along with the nephroureterectomy at the same setting?

Makarand Khochikar: Basically when we discussed with him, they were not ready to accept that this is part-and-parcel of the entire disease and we could finish it in one go. Even the anesthetist, he thought, "Just find out exactly how things are," because he presented, if you look at it, with left loin pain and hematuria. So the kidney hydronephrotic was very palpable. We all thought that that's more symptomatic, and let us keep that option whether we can sort of preserve his bladder. So we staged in such a way, do a TURBT, finish the kidney part, and then subsequently take care of bladder, in case [inaudible] keeps on recurring or shows further progression. So I'm sure... so that could have been another option. He could have a nephroureterectomy along with cysto-prostato-urethrectomy, but considering his age and comorbidities, we thought the stage-wise would have been better, but I'm sure we could have done that as well.

Ashish Kamat: Great. Thank you so much, Dr. Khochikar for sharing this interesting case with me and the audience for UroToday. As always, really appreciate you taking the time. Stay safe and stay well.

Makarand Khochikar: You too, as well, Dr. Kamat. Thank you.

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