Dr. Firas Petros - Kidney Cancer and Genetic Testing

Transcript

Voiceover:
Welcome to Prescribed Listening from the University of Toledo Medical Center. Each week, UTMC providers sharing insight into their medical specialty. This week, Dr. Firas Petros.

Dr. Petros:
Hi. I'm Dr. Firas Petros. I'm a urologist and specialized in urologic oncology. I trained at University of Texas MD Anderson Cancer Center, where I finished my urologic oncology fellowship. And before that, I gained my residency at Ohio State Wexner Medical Center. Upper tract urothelial carcinoma, it's basically a cancer of the lining of the urothelium that lines the renal pelvis inside of the kidneys. The ureter, the tube that take the urine from the kidney to the bladder, as well as urothelial carcinoma of the bladder can happen in the bladder itself and in the urethra, the urine channel where the urine passes to the outside, whether in the female or in the male. So upper tract urothelial carcinoma, it's often a disease of elderly, usually the age above 60, 60s to 70s or 80s. More commonly seen in patients who are smokers or they have other risk factors, chronic rotation by a stent placed for other reasons or history of prior pelvic radiation or repeated infection, stones, or some patient if they take lots of narcotic pain medication or Chinese herbal medication.

Dr. Petros:
So the treatment depend on the grade and the stage, the treatment of upper tract urothelial carcinoma. So, if a patient has low-grade urothelial carcinoma and of a small volume can be treated endoscopically, preserving that kidney unit for the patient. Of course, patient has to be compliant with subsequent follow-up imaging, surveillance ureteroscopies. Otherwise, if it's still low grade but voluminous tumor, where it can not be treated by endoscopic resection, then the standard of care will be radical nephroureterectomy, that is for low grade. If it's high grade upper tract urothelial carcinoma, also we look at the stage. Often, staging of this cancer are difficult to do because of the nature. Ureteroscopic biopsies are small, so we combine imaging studies, predictive nomogram to get the accurate staging, and if we feel this is high grade and advanced stage, then patient often will receive neoadjuvant chemotherapy followed by radical nephroureterectomy.

Dr. Petros:
In certain circumstances, we can forgo the neoadjuvant chemotherapy and proceed right away to radical nephroureterectomy and reassessment based on the final pathology for adjuvant chemotherapy. So, low-grade cancer based... This is pathologic assessment based on how the tumor cells looks under the microscope. So if they have high nucleus to cytoplasm ratio, irregularity of the cytoplasm and dysmorphic nuclei so often term high grade. But if they don't have these features, usually they are low grade. So the grade also correlate with the aggressiveness of disease. Often, patient confused, they come to the clinic. If we ask him the history, whether the patient himself or family member, or he or she, they mention he has a kidney cancer.

Dr. Petros:
So kidney cancer divided into urothelial carcinoma, which is cancer of the lining as we mentioned, of the renal pelvis, ureter, or there's the other type of kidney cancer, it's of the meat of the kidney itself, of the renal parenchyma. So that's what we call a renal cell carcinoma. That's completely different type of cancer than the urothelial carcinoma. It arises from, as I said, renal parenchyma. The most common histology is clear cell renal cell carcinoma about 75%, and there is papillary, chromophobe, unclassified. The treatment is completely different. So I mentioned for urothelial cell carcinoma, we need to do nephroureterectomy, taking the kidney unit with the entire ureter all the way down to the bladder, we call it a bladder cuff excised, a piece, or excised the urethral orifice with the surrounding tissue. But for renal cell carcinoma, if we can not save the kidney, if a patient going to go for a nephrectomy, which is kidney removal, then only we remove the kidney and part of the ureter, not necessarily to chase the ureter all the way down to the bladder. So, that's completely different surgery, and then that's one surgery.

Dr. Petros:
The other procedures that we do, if it's a smaller renal mass, less than three centimeter, two centimeter, or even less, we can just do active surveillance. That's one option. The other option, if it's two, three, or we have evidence it's enlarging mass, then we can do a partial nephrectomy. Or if a patient not a candidate for surgical resection, then we'll do needle ablative strategies, treating the mass with either heat, we call it radiofrequency ablation, or freeze it, we call it cryotherapy. In addition to radical nephrectomy that we do often when we can not save the kidney, if a partial nephrectomy is not feasible due to the size of the tumor invading into the kidney itself, there is no salvageable tissue left if we're going to do the partial, then yes, the entire kidney need to come out, that is a radical nephrectomy.

Dr. Petros:
We do all these types of treatment when the disease has not metastasized. If the disease has already metastasized upon presentation, if a patient comes with a metastatic disease, then we assess typically lab values, we assess performance status of the patient. If a patient has excellent performance status and there are certain lab parameters that we look for, for example, he is not anemic. He doesn't have high calcium. His other parameters such as the platelet count, the LDH are not elevated, then he still can with metastatic disease. And if he has low-volume metastatic disease, he can still go to upfront, we call it cytoreductive nephrectomy, which means we are trying to reduce the tumor burden by taking that kidney out. Despite he has, let's say, one or two spots in the bone or lungs, but if he has high-volume metastatic disease and he has poor performance or intermediate performance status, then he will go for systemic treatment.

Dr. Petros:
Nowadays systemic treatment is not with chemotherapy, but immunotherapy, and we use some other agent called tyrosine kinase inhibitors. Once he received at least three or four cycle, reduce the burden of his disease, and we reassess his response to therapy with staging scans, if he doesn't progress and he's doing fine, then he will come back for the cytoreductive nephrectomy. Smoking is a risk factor for kidney cancer. Obesity is another risk factor. There is something called hypermetabolic syndrome, where patient... We often we see it in obese men or women, they have high blood pressure or diabetes. In addition to smoking, some other risk factors such as genetics or hereditary. When we see renal cell carcinoma in younger patients, less than the age of 46, then we have to think of hereditary factor. But yes, for cancer there are, and then most of the cases, and kidney cancer are sporadic, meaning it's just a bad luck. Some mutation happened and not necessarily with a family history.

Dr. Petros:
So the genetic testing of our new avenue for multiple cancers and treatment of multiple cancers, especially nowadays, there is more evolution of the treatment to target certain signals or molecular markers for different types of cancer. So let's take an example. So for prostate cancer, genetic testing is very important. It has been previously mentioned in the guidelines as suggested, but the most recent update of these guidelines as a year ago or even longer, now it says recommended. So who should get genetic testing? Who should not get it? So certainly, if a patient diagnosed with aggressive type of prostate cancer, we call it high grade or high risk, Gleason 8, 7, 9. Regardless of their family history or the biopsy showed certain features on histology, we call it cribriform histology, then these patients should get genetic testing regardless if they have family history or not.

Dr. Petros:
Then, the other population in a prostate cancer, if a patient intermediate risk or they have low risk, then you look also on the pathology of the biopsy or you look if they have family history. But any patients with high-grade disease, high risk or very high-risk prostate cancer, genetic testing is recommended by the guidelines. And why it is important, again, I'm speaking now only for prostate cancer, it affect the treatment. So if this patient, for example, in the years to come, he would develop metastatic disease and he has certain mutation detected on his genetic testing, then there are certain agent now developed that can target that mutation and potentially cure the patient or control his disease.

Dr. Petros:
The other important aspect, about 50% of the genes, so let's say if the patient tests positive, there's 50% chance he can pass these genes to his children whether male or female. And we know there are certain genes in men can cause prostate cancer such as BRCA1 and BRCA2, BRCA genes, and in female can cause of breast cancer. So regardless of the patient has only a biological daughter, yes, she can get a breast cancer because he had prostate cancer himself. In upper tract urothelial carcinoma, genetic testing also is important. So if we see a young patient, it doesn't have the source factor that I mentioned to get upper tract and we diagnosed him with upper tract, then yes, they should raise a red flag why this happened. One of them is hereditary. So an upper tract urothelial carcinoma, there is Lynch syndrome, which is a condition where patient is predisposed to have colon cancer, endometrial cancer, pancreatic cancer, and melanoma.

Dr. Petros:
And I did have such patient, I tested her, she tested positive for Lynch syndrome. So, now she's going through screening process for all these other types of cancer. And same thing, the patient children now at risk of developing Lynch syndrome. And we have seen it, I've seen it in my training patient tested positive for Lynch. And then one of the daughters also tested positive for Lynch. So, it's very important. In kidney cancer, as I mentioned, yes, renal cell carcinoma. It's not a disease of young people, but if we see a patient, and I did have that patient too here at the University of Toledo. He was found incidentally to have a small renal mass upon a CAT scan done for a kidney stone, went to the ER, emergency room, was having some flank pain and he had a small stone that he passed, then there was a small renal mass. We followed that mass. Mass was growing. Potentially, we did a partial nephrectomy. We removed this mass, came back renal cell carcinoma. The age of the patient? 40. He shouldn't get it, right?

Dr. Petros:
So I sent him for genetic testing. He turned positive for a syndrome called Birt-Hogg-Dube syndrome. Now, his children are at the risk of developing renal cell carcinoma, so they have to go for screening early so that they can be diagnosed early before metastasis because that's the important of genetic testing. You screen early, you detect early, you prevent potentially metastasis and death. A germline testing, as I mentioned in prostate cancer, if you detect one of these genes, the BRCA1 or BRCA2, so now there is a treatment called PARP inhibitors. One of them approved by the FDA, olaparib, Lynparza, so can be used for patient with castrate-resistant prostate cancer. Let's say, a patient has progressed, he has metastatic disease and progressed on hormone therapy, progressed on the traditional chemotherapy plus the hormone therapy and his PSA is not responding. And when we checked his testosterone, yes, he isn't in a castrate state, but PSA continues to go up.

Dr. Petros:
So in this patient's population, if a genetic testing was not done, certainly it's an indication because one of these such therapies that's available now approved by the FDA is olaparib, which is a PARP inhibitor, it targets these mutations whether they are in the germlines, and the patient has inherited or they are somatic in the tumor itself. So yes, germline testing is very important. So genetic testing can predict cancer risk stratification, again, it's for the patients at earlier stages. Probably it will not be used if he... I mean, we can use the information obtained for the patient himself even if he's at earlier stage of his diagnosis, but it will be more used and the patient himself when he will develop metastasis. The example, prostate cancer patients, and I do have a patient like this. After surgery, he has undetectable PSA, meaning he has no evidence of prostate cancer, but on a baseline level, on a germline level, he tested positive for BRCA2 BRCA gene.

Dr. Petros:
So yes, I will not be starting the patient on a medication now because basically his PSA undetectable, he is in remission or no evidence of disease. Again, I can not say I cure the patient because it hasn't been 20 years since his surgery, has been only a year, but since he tested positive, his children now at risk if he has male children at risk of developing prostate cancer. So it will be utilized to screen his sons to go for screening early with a PSA, follow with your primary care and then any elevation, any rise in the PSA, then his children, yes, need to get potentially diagnosis to make sure they don't have prostate cancer and potentially treatment. So again, that is how genetic testing. If it doesn't help the patient himself at that time point, but it will help his children.

Dr. Petros:
The MRI ultrasound fusion biopsy, the studies came about in 2013. Basically, at that time point, we were seeing more patients getting... They have elevated PSA or suspicion they could have a prostate cancer whether based on the PSA or rectal exam. So they were having the standard biopsy or we call it office biopsy, systematic biopsy, just with ultrasound. And then a portion of these patients, they were having their cancer missed. They will have a negative biopsy and then their PSA continue to rise. So that's when the MRI entered the field by imaging the prostate, identifying the location of the lesion. And some of these lesions are up in the prostate, we call it anterior lesion or front lesion and will not be reached by the standard biopsy.

Dr. Petros:
On ultrasound, sometimes you can see the lesion, the area or the suspicious area, suspicious of spot. Unless this area really big in size, then you can see it with some degree of certainty, but it's not as sensitive to detect these lesions compared to the MRI. So the MRI kind of revolutionized the field in terms of allowing us to fuse the image of the MRI that is obtained free hand with real-time ultrasound to create a 3D map of the prostate, if you will, kind of GPS signal to go and target these areas seen on the MRI. So it increased the accuracy, the detection rate and what we are really interested in detecting the high-risk cancer, so there are multiple high-quality studies, the level one evidence, we call them randomized trial, showing that MRI ultrasound fusion biopsy is superior in detecting high-risk lesions at the expense of detecting less low-risk disease because, once again, we are not interested in detecting low-grade cancer.

Dr. Petros:
Patients will not die from a low-grade cancer, but certainly they will develop metastasis and potentially death from prostate cancer if they have high-grade disease that was missed. So yes, it revolutionized the field in terms of better accuracy, higher sensitivity to detect high-risk disease and detection of low-grade disease. So we have been using it here for the last two years at the University of Toledo. We'll counsel the patients regarding genetic testing, risk benefit, and the advantage. Certainly cascade testing is on the horizon if he tests positive and then, certainly, this is going to follow with a referral to a genetic counselor. So every patient I test, and if he tests positive, I will send for a genetic counselor.

Dr. Petros:
There is something called risk of genetic discrimination, unless this information of his test disclose to, for example, in his employer or different company and then when he went to apply to that job. But most of the time, these patients are either Medicare patients, so that risk doesn't really apply to them. And then, regarding the cost, there are different companies that offer genetic testing. But the company that I work with, they have a fixed price. It's $250 regardless of their insurance and most of the insurance Medicare cover the genetic testing, and then what also unique about this company, they offer test free for the family members. So children, sisters, and brothers if they need to get tested usually they have a grace period from the day the issue of the report. I believe it's around 90 days, but it correlate highly with the pathologic finding or with the stage of the disease. When we see a patient to who tests positive, sometimes this can also point to hereditary factor, especially if we diagnose a patient with aggressive disease in his early ages, like at the age of 50, 55.

Dr. Petros:
Regarding research in the field of genetic testing, for example, I looked at the patient that I had been tested to see who followed with the genetic counselor, who did not, and what were the preventing factors. So I find that one-third only of the patient who tested positive for germline testing, they did follow along and they met with the genetic counselor. And this is including all commerce or cancers not only prostate cancers. And I found more the percentage of positivity in prostate cancer around 12% and the other non-prostate cancers including kidney or epithelial carcinoma was a little bit higher. So yes, so we are trying to determine what factors led the patient not to follow. Is it anxiety? Is it a cost? Is it inconvenience? Is it because of the pandemic? So, these are one of the research area that I had been working on. And also, there are other research avenues that I'm working on. One of them, for example, the use of immunotherapy to selection of patients for certain type of immunotherapy and their outcome in urothelial carcinoma. So these are some of the research that I've been working on.

Voiceover:
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