Urologist based in New York who has been practicing for 26 years
Dr Luangkhot is a urologist based in New York who has been practicing for 26 years. He specializes in male and female urinary tract and male reproductive organs, and manages 500+ prostate cancer patients a year. He is a recognized published researcher where he has offered developments in urology practices, such as the placement of urinary catheters and collagen alternations in the corpus cavernosum of men with sexual dysfunction.
Section 1: Breakthroughs in Prostate Cancer Diagnosis
1.1. What is the current state of prostate cancer diagnostics?
I think PSA is still the marker that basically triggers the discussion, evaluation and diagnosis. It’s almost like a pendulum that swings both ways. When PSA first came out about 30 years ago with the cut off being 0-4 and then as soon as you get a PSA of 4.1 you would get a biopsy. As a result of that, I think we detected a lot of prostate cancers. Unfortunately, we realized after about 20 plus years that we were over-diagnosing and over treating. Leading to the pendulum swinging the other way.
I think a lot of people in Europe would say, “Oh, stop doing PSA’s. It has a grade C or grade D type of value. You probably shouldn’t even do it.” I think there was a huge study that shows that whether or not you do PSA it didn’t make a difference; the patient’s still going to die anyway from whatever they need to die from.
Now I think the pendulum is probably swinging back toward the middle, in a sense that we realized that by under-doing the PSA, we are missing a lot of patients that should have been detected. Not only are we now doing more and being more aggressive; we are also seeing more patients with advanced disease or metastatic disease. So, that’s basically the diagnosis.
For evaluation, we have a lot of biomarkers and new ones seem to be showing up every week. But I think at least for us nowadays in the U.S. I think the PSA elevation probably prompts an MRI first, when an MRI is negative then you sit on the patient; the MRI is positive then you either do a transrectal ultrasound or MRI guided prostate biopsy.
1.2. What is the impact of the introduction of new biomarkers?
Well, there’s urine, there’s blood, there’s tissue. There’s so many of them I couldn’t keep up, there was a PCA3 at one point, and now we have Exosome DX for the blood tests. I think there was some something coming down the pipeline about a blood biopsy, or liquid biopsy. Maybe you can get something off of the patient’s serum sample. There’s a tissue biopsy. Those have been around for a while.
The PCA3s fell off the popularity index because it didn’t look like it was really panning out to be such a great thing. Right now I’m evaluating Exosome DX, which is again, a urine test in the office that does not require a prostate examination. Furthermore, there is a new one called Decipher made up by Decipher Biosciences. I think that’s a tissue. I think people are kind of excited about this or we’re about to try it, to see whether or not it makes any difference. We are going to compare that to Oncotype DX and some of the other stuff that came before them.
1.3. What is the impact of promise of ‘office based’ tests?
I think only time will tell because we don’t have enough data on it. Everything that is being presented to us is based on previous research and data, but it did look promising and we are all trying to find ways to avoid a prostate biopsy or avoid picking up so-called ‘insignificant prostate cancer.’ I think the thing that’s driving us the most, is, not only are we picking up insignificant prostate cancer, but because of antibiotic resistance that’s popping up in the U.S, and there’s a significant morbidity involved with somebody becoming sick with a urinary tract infection or sepsis after a prostate biopsy, then the antibiotics that we use to prep the patients for biopsy are no longer adequate.
As a result to set the patient up for prostate biopsy is quite labor intensive nowadays. A lot of people go as far as rectal cultures, urine culture, and then giving all kinds of antibiotics to prevent infection. Historically the prostate biopsy related infections used to be less than 1%. I think in that area, it has gone up to three, maybe even 6%. That’s not something that we can laugh at.
Maybe all these factors are driving all these markers that we’re trying to do to again, avoid insignificant cancers and also avoid unnecessary prostate biopsies.
1.4. What are the current issues with diagnosis via ultrasound biopsies?
Unless it’s not approved by the insurance, only a patient with elevated PSA or serially rising PSA’s could become a candidate for evaluation. In other words, the usual landmark is young patients, less than 65, patients who have 10 or more year of life expectancy, are the usual guidelines.
For those patients with either rising PSA’s or PSA that’s elevated for their particular age range, we would get an MRI first, assuming, that it’s approved by the insurance. If the MRI is negative, we stop and just monitor the PSA’s over time.
If the MRI shows that the lesion is pretty large i.e. 10 millimeter or 20 millimeter or more and because we know the location of the quote-unquote lesion, then we would target that particular lesion a little bit more on the ultrasound in addition to doing the standard random prostate biopsies or something else.
The ultrasound is good in a sense that it allows us to visualize the prostate size, we use the ultrasound to give the local anesthesia for patient comfort and definitely guide the needle to the appropriate area of the prostate for biopsies. The downside of that is that it’s completely random. Even when you have the MRI to back it up to tell you exactly where the lesion is, you normally cannot see it on the ultrasound. So, to me, it’s still considered random.
1.4.1. Can MRI assisted biopsies solve these problems?
If the MRI is positive and the lesions are rather small, 10 millimeter or less, we are always afraid that if we did a simple transrectal ultrasound guided prostate biopsy, we might miss that lesion, as a result of that we would do a MRI fusion ultrasound guided prostate biopsy.
MRI is good, but not foolproof. I think that we’re talking about excess of 95% accuracy, but you’re still left with the 3 to 5% false negative.
It’s not cheap. However, they did a study that showed that by doing MRI and avoiding a prostate biopsy then the savings can be about $13 million in the U.S.
Here they are just comparing biopsy versus MRI, but I have a feeling that the difference will be even more if you count the patients who undergo either serial biopsies or become sick and either required hospitalization because of sepsis, or die from the biopsy so then the difference will be much more.
And MRI, some of them are not covered by the insurance company. Also it does take quite a bit of preparation to get the patient on the table. Even if it’s approved by the insurance company, some of the insurance companies would insist on prior authorization, so, that’s an extra step that you have to do in order to again, get the patient to have the study done.
There’s a lot of prepping involved on the part of the patient, and that is also psychologically quite traumatizing. If the lesion is small then you have to fuse the MRI with the ultrasound machine and then set the patient up for MRI fusion, ultrasound guided prostate biopsy, which in itself is not simple.
I would say that 80% of biopsies are ultrasound, and 20% are MRI assisted, maybe even 90% and 10%.
1.5. What are the next breakthroughs in prostate cancer diagnosis?
I think I would break it down to evaluation and then diagnosis or assessment, in the sense that we talked about the liquid biopsy. We talk about serum blood test. We talk about urine blood tests. Those basically tell us when are we going to do the biopsies or not. I think to me, that’s evaluation or screening, whereas the actual biopsy itself would still be a diagnosis portion of the evaluation.
I think more and more studies are coming out, more and more tests are coming out. We’re hoping that this would narrow down further the number of patients who actually will need a prostate biopsy because it’s indicated as opposed to something random and they end up with unnecessary prostate biopsies as a result.
As far as diagnosis is concerned, I’m hoping that eventually even the ultrasound machine would be able to detect lesion so and then we don’t have to subject the patient to MRI or going the other way around. Let’s say the patient has an MRI and has a lesion, you can just biopsy the patient immediately using the MRI machine without having the patient have to come off the table. We have to fuse the two studies, but I think that’s a while off yet.
Some of the other tissue biomarkers, again, people are honing it to such an extent that we’re trying to probably use information to say, “Well, this patient has prostate cancer, but probably not high risk. We can probably follow these patients actively,” this is so-called active surveillance, “without having to do anything.”
In fact, that’s my hope anyway, because the current protocol for active surveillance still calls for a repeat prostate biopsy every one to two years as you follow these patients, which to me is a little bit of an overkill, especially, let’s say the patient feels fine, there’s no new nodules on prostate examination or the PSA has remained relatively stable, just goes up and down, up and down, but it really doesn’t keep on creeping up.
I don’t think that is a current recommendation from the AUA. I think even if everything is still the same, they still insist that you get a biopsy. I think it used to be every year. I think they may have relaxed the rules a little bit. It may now be every two years. Personally, I trust my PSA. And if the patient has been clinically stable, and PSA is stable, I tend to just follow the patient as opposed to subjecting them to another biopsy.
Section 2: Breakthroughs in Prostate Cancer Treatment
2.1. What is the current state of hormone therapy?
I would say hormone therapy is still the standard of care for a patient with stage three or stage four disease or patients who want to be treated, but are refusing other forms of localized therapies such as surgery or radiation or active surveillance. But the problem that we’re facing right now is a shortage of hormone therapy, believe it or not. Like normally we would be using Lupron six months injection because it’s convenient for the patient, convenient for us, patient just have to see us twice a year. The problem is there’s a shortage of six months, and now we’re back to the one month injection. I’ve seen a few that would approve us for the three or four months, but even then it’s a pain in the butt because you have to get the prior authorization for the one month, every month. And the patient has to come back to us every month. So, that’s where the current state of hormone therapy is right now.
It’s also interesting, I’m considered the older generation of urologists. We used to, before these injectables and these oral pills came along, offer the patients scrotal surgical, orchiectomy, the removal of the source of male hormones, testicles in this case. Somehow the pharmaceutical companies must have done a good job on the younger generation of urologists, who sort of balk at the idea of having to remove somebody’s testicles, even though it’s a very simple surgical procedure, a cheap procedure, and I highly recommend it for elderly patients who are no longer sexually active, but I think to a lot of young urologists, the thought of having to remove a patient’s testicles was somehow quite unacceptable. I don’t think these young urologists realize how much more expensive it is to inject these patients with hormone therapy year-in and year-out as opposed to a simple surgical procedure.
2.2.What are the new clinical developments in hormone therapeutics?
Before the so-called novel anti-androgens came along, we just had the basic Bicalutamide and Lupron being the major two contenders here, but obviously the treatment was not perfect. So, patients eventually evolved from so-called castrate sensitive, hormone sensitive prostate cancer to castrate resistance.
Then now we have like four or five novel anti-androgens that are more specific and more effective. As a result of that, the two schools of thoughts would be; the patient who failed Lupron and Casodex probably should get these anti-androgens on top of continuation of traditional hormone therapy. There are also a lot of providers, who, probably are either paid by the pharmaceuticals to market the fact that, “Oh man, I think we should jump over to anti-androgens right off the bat since they are much more effective.” But even though they are much more effective, I think you follow these patients four years out eventually it will fail. As a result of that, I think we’re looking at even more novel therapy to combat the eventual emergence of these late stage resistant cancers. And we’re talking about immunotherapy, we’re talking about chemotherapy, maybe better hormones. I think these are probably the three main prongs right now.
2.3. What is the current state of immunotherapy?
There is a vaccine called Provenge, which is immunotherapy for prostate cancer. So, it was popular maybe about five years ago as a way to sort of like slow down the growth, or the progression of prostate cancer and the people who push it really big believers in it. But it also just so happens that the people who push them are also the people who write the papers and who ran the research.
And when you look at other faculty members who had looked at the data, all the members who have to comment on the value of Provenge, they balked at it, not to mention the fact that there’s really no good way of measuring the success of the therapy because it doesn’t affect the PSA, number one. Number two, it’s time-consuming to administer and, number three, I think it costs probably like a hundred thousand dollars a year in the U.S. Yes, compared to other chemotherapy, it’s probably considered cheap or equivalent, but that sort of fell out of favor.
2.4. How effective are inhibitor drugs?
We’ve seen that in urothelial carcinomas, cancers of the renal pelvis, cancer of the uterus and definitely cancers of the bladder. And so in that sense, we are quite excited that maybe this would be applicable to prostate cancers as well, but I don’t think that that has gone as far as urothelial cancers yet.
2.5. Is the future of treatment in hormone or immunotherapy?
Prostate cancer is one of these tumors that grow forever, and sometimes we’re talking 25 to 30 years. As a result of that just look at the answers over the course of a few months to a few years, probably not fair. Again, we’re just going to have to let the scenario plays out.
Let’s just say, I have a feeling that traditional hormone therapy will probably still be around and they probably will be considered first-line; the novel anti-androgens may eventually replace the traditional oral anti-androgens, again, if the scenario plays out that it is superior and the pricing becomes acceptable and the side effects become acceptable.
I would say the same thing for immunotherapy or the newer treatment regimen. It all depends on where it’s going to land on either they might stay as a treatment for late stage disease, or they might move earlier and earlier in the diagnostic scheme.