Urologic Oncology

SLIDES & TRANSCRIPTS
Saturday, December 6, 2003

Endoscopic Management of Upper Tract TCC

Thomas Jarrett, M.D.

Slide 1:

I'd like to thank everyone from NIH for helping us sponsor this and inviting me, especially Peter. Peter was our Fellow last year, and did a wonderful job, and we are happy to see him down here.

I'm going to talk about -- Peter wanted me to keep it short, and so I'm just going to talk about what is the state of endoscopic management of upper tract TCC in 2003.

As we all know, it is a very uncommon disease. Most of these patients should be treated with nephroureterectomy. I did the patient numbers. It is hard to get hard fast conclusions, but we certainly get a better idea of what we should be doing.

Slide 2:

What are the indications? I think obviously, diagnosis is imperative. I think ureteroscopy is not indicated if you have an obvious filling defect and a positive cytology, but any equivocal case, I don't think there is any excuse not to put a ureteroscope up and confirm your diagnosis.

Management of low stage grade tumors, especially in people at risk for renal failure, and compliant patients. These people require lifetime follow up, so if they don't meet these two criteria, you need to think very hard about doing this.

I think something that has come about more recently is management of high grade tumors in two populations, one, those with medical contraindications to surgery, even though laparoscopic nephroureterectomy has provided a less invasive option for patients with high grade disease, and patients with metastatic disease for local control. Unfortunately, high grade tumors in upper tract TCC bleed, they cause problems, and it is not something you can just watch. You can try chemotherapy and other things, but you may have to do something in the face of metastatic disease, and this is a good option.

Slide 3:

I want to go through some of the controversies that I think have settled out. Is ureteroscopic biopsy accurate? I think there have been two good studies here. Dr. Keeley with Bagley up at Jefferson, and Dr. Datschmann out of USC with Jeff Hoffman, who is one of the pioneers in doing this, found both that biopsies are 90 percent accurate and each one out of 20 was up stage and one out of 20 was down stage. So I think overall, the ureteroscopic biopsies, if done properly, are accurate.

We try to maximize the specimen that we get, and I find the best way is to use the Seguro basket to get a big chunk of tissue for the biopsy. The disadvantage is, it is hard to get deep biopsies, so you can't do staging, but I think especially with this disease, tumor grade is the most important.

Slide 4:

Controversy-Seeding of Urothelial Surfaces. I think Dr. Bagley showed pretty well here, he had 13 patients who underwent multiple ureteroscopic procedures followed by immediate nephroureterectomy, and no evidence of tumor seeding at other sites. So I think we have seen cases that disseminated after ureteroscopic, but I think it is a pretty rare occurrence.

Slide 5:

Does ureteroscopy disseminate tumor? By doing ureteroscopy in a high grade tumor, are you putting them at risk for metastatic disease down the road? This from Cleveland Clinic here, Dr. Novick with Ben Hendin, one of his residents, looked at 96 patients who underwent nephroureterectomy with or without prior ureteroscopy, and it shows no difference in survival between these two populations. So once again, I don't think it is dangerous to do so, and in many cases it is helpful in confirming the diagnosis.

Slide 6:

This is one area that I think is very concerning, though, if you choose ureteroscopic therapy beyond just diagnosis. These are three early series here. This is the Keeley with Jefferson series. This is the Mayo Clinic series, and this from South America .

The recurrence rates here were 19, 46 and 29 percent, and mostly short term followup, even though they had some long term. You see the nephroureterectomy rates, and I think this is based on patient selection.

But Jeff Hoffman recently did an over ten year follow up and most of his patients had at least a five or six year follow up. He found a 90 percent recurrence rate with an average of 3.3 per patient. So I think that this is something to be taken very seriously when you commit somebody to endoscopic therapy, especially with a normal contralateral kidney.

In my experience it has not been this high, but it has been higher than these. These patients that have even low grade tumors, you can go back and keep resecting them, but they are going to recur. There is a high incidence of these recurring, and I think you have to counsel the patients in that preoperatively.

Slide 7:

Conclusions. Ureteroscopic approach. I think it is the preferred method of diagnosis, safe and effective treatment for the properly selected patient. I think very important, properly selected. Biopsy can actually grade tumor, but not provide staging. Recurrence in bladder and upper tract require livelong endoscopic followup. So I think this is something very important to keep in mind when you embark on endoscopic therapy.

Slide 8:

I'm going to switch to the percutaneous approach here. I'm just going to go through the three largest series here. Once again, very similar to ureteroscopic. Once again, the recurrence rates, nephroureterectomy rates are fairly similar. Once again, with the percutaneous approach, it is an invasive procedure, and there is always the concern with tumor seeding, since you are violating a closed system.

Slide 9:

If you look, this is a recent series from Dr. Gall, 24 patients that came out with long term follow up. The one thing to keep in the back of your mind, four out of five high grade patients in this series died of disease after subsequent nephroureterectomy. So it raises a suspicion. They have a poor prognosis anyway, but if these patients had just gotten immediate nephroureterectomy rather than percutaneous therapy, would they have done better.

And long term, four required immediate nephroureterectomy, six of 15 required subsequent nephroureterectomy. So you are looking at a high number of patients that are going to end up with nephroureterectomy anyway, so you really have to consider this therapy strongly before you proceed.

Slide 10:

I think the most important, as with any type of tumor of the upper tract -- this is when I was at LIJ with Dr. Smith; we looked at our series. What I want to point out is, as you would expect, the prognosis was much worse with increasing tumor grades. With grade one disease, we had recurrences, but they were not usually metastatic, but with grade three disease, we had four of 13 patients die of subsequent metastatic disease. So once again, you have to be very cautious when you embark on this therapy, especially in somebody with higher grade disease.

Slide 11:

We looked at -- but the other side of the coin is, high grade disease patients are going to do poorly no matter what you do. We compared all the percutaneous resections with LIJ with all the nephrouterectomies at Hopkins . For all three grades, we did not see any statistically significant difference. But I will say that I think that especially for grade two and three, you have to offer a nephroureterectomy in an otherwise uncomplicated patient as the first line choice for sure, and grade one in selective situations.

Slide 12:

Controversy. Seeding the nephrostomy tract. There have been isolated case reports, all with high grade tumors and subsequent metastatic disease also. But if you look at the two largest series, our series and Christopher Woodhouse from England , there was no known TCC tract infiltration in that series. We had one single case of squamous cell carcinoma.

I suspect a lot of these patients however died of metastatic disease before they developed tract seeding, so I think it can occur, but fortunately it is fairly uncommon.

Slide 13:

Conclusions to the percutaneous approach in 2003. Safe and effective in properly selected patients, low grade disease, risk for renal failure, able to grade end stage tumors, can remove large volumes of disease, higher morbidity for sure when compared to the ureteroscopic approach, and lifelong surveillance with endoscopy required.

Slide 14:

Controversy of followup. I just want to mention here, if you are going to follow up, Dr. Bagley when he did this, 75 percent recurrence not discovered radiographically, and only discovered with uteroscopy. So if you embark on this, radiographic follow up is not accurate in detecting early recurrences.

Slide 15:

In conclusion, endoscopic management should be reserved for well selected patients. I think that is where we have failed in the year 2003. We are really not much closer in selecting which of these patients are going to be bad actors and at risk for metastatic disease and which patients aren't.

Successive therapy is dependent on the biologic potential of the malignancy, and that is what we really need to do. We need to find ways that we can better predict the biological malignancy of this therapy.

High cost for sure associated with this therapy. You have to surveil these patients life long, with not just radiographic follow up, but endoscopic follow up. I think the key is, as I said, molecular profiling is necessary for patient selection.

Thank you very much.