“Male Lumpectomy” Emerges as New Option in Prostate Cancer: An Interview With E. David Crawford, MD

OncologyLive, August 2012, Volume 13, Issue 8

Targeted focal therapy offers some men with localized prostate cancer a solution between active surveillance and definitive treatment with surgery and/or radiation.

E. David Crawford, MD

Professor, Surgery and Radiation Oncology, Head, Urologic Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO

Prostate-specific antigen (PSA) testing often detects smallvolume tumors, but it cannot determine the aggressiveness of the cancer. This leaves patients with a difficult decision between active surveillance and definitive treatment with surgery and/or radiation.

An emerging technique known as targeted focal therapy now offers some patients with localized prostate cancer a middle ground between these two options, according to E. David Crawford, MD, professor of Surgery and Radiation Oncology, head of the Section on Urologic Oncology, University of Colorado Health Sciences Center in Denver.

Referred to as the “male lumpectomy,” targeted focal therapy treats only the tumor cells, not the entire prostate. The procedure begins with a three-dimensional (3D) mapping biopsy, which identifies the location of the tumor cells within the prostate. Once the cancer is located, there are multiple methods available to destroy the tumor cells, including cryotherapy, high-intensity focused ultrasound, intensity-modulated radiation therapy, brachytherapy, and photodynamic therapy.

During the 5th Annual Interdisciplinary Prostate Cancer Congress in New York City in March, Crawford discussed the potential for targeted focal therapy as an effective option.

Although he supports PSA testing, Crawford said its inability to determine which tumors require treatment frequently leaves patients and physicians in a difficult predicament. Small-volume tumors are often detected, but with no accompanying knowledge of which tumors are indolent, the course of action is unclear.

He said that active surveillance is given a lot of “lip service,” but that studstudies have shown its use has actually decreased over time. Patients are often unwilling to do nothing when they know they have a tumor inside them. Given this reality, he said that targeted focal therapy offers some men with localized tumors a solution between active surveillance and definitive treatment with surgery and/or radiation.

The Cryocare CS Surgical System is utilized in cryotherapy. It delivers cold temperatures to targeted tissue, monitors temperatures in the surrounding tissue, and captures images of the affected areas. The system was developed by Endocare, a subsidiary of Texas-based HealthTronics, Inc.

Crawford further discussed the targeted focal therapy approach in this interview with OncologyLive.

OncologyLive: How do you determine which patients are eligible for targeted focal therapy?

Crawford: If we set the stage, what we know is that in men who undergo biopsies, 30% to 50% of them will have cancers that are deemed at least “low risk” on the initial biopsy. Low risk would be somebody with a PSA that’s less than 10 and a Gleason score of 6 in one or two cores, not involving more than 20% of the cores. I would say that describes anywhere between 20% and 50% of the patients that we see with prostate cancer. And so, for these individuals, rather than rush into surgery or active surveillance, we recommend first getting more information.

In every other cancer that we treat, we get more information. For example, we get bone scans and PET scans in lung cancer and breast cancer. However, in prostate cancer with a low PSA, PET scans and bone scans are a waste of time because they are looking for metastatic disease. We want to know what’s going on in that prostate. We want to know whether this is a cancer that we can just watch, a cancer in which we can just treat a small area of the prostate where the cancer is located, or a cancer that requires more aggressive treatment. And so that’s where the 3D-mapping biopsies come in.

With mapping biopsies, we go in transperineally, under the scrotum directly into the prostate. By going transperineally, our risk of infection has been very low and we’re able to sample the whole prostate, unless it’s huge, and then the pubic arches are in the way so we can’t get there. But if you have a prostate that’s 40 to 90 grams, with 90 grams being a large prostate, we can get the whole thing.

So what we do is place a grid template over the perineum, and, guided by transrectal ultrasound, biopsies are obtained from specific areas of the prostate. We obtain about two biopsies per gram of prostate. So I roughly know if somebody’s got a 40-gram prostate, it’s going to be 80 biopsies. And sometimes with these cores, since they’re only 17 mm, you actually have to do two of them so you get the whole length of the prostate. So you get the one near the apex and one deeper.

We mark and label the biopsies, and then using a computer program, we can create a 3D reconstruction of the prostate that includes the location of the cancer. We then decide whether or not this is something we can go after with targeted focal therapy. And I’ll tell you, about half of the patients turn out to be eligible for the targeted treatment. In the other half, we find things—cancers on both sides, high-grade cancers—and say, “You really do need to have a radical prostatectomy or radical radiation.”

A patient who presented with an elevated prostate-specific antigen level and a negative transrectal biopsy was evaluated with a threedimensional mapping biopsy. A microfocus of low-grade cancer in the right apex (Gleason 6), photo at left, was discovered. The photo at right illustrates a hypothetical freeze pattern obtained by using targeted focal therapy (shown in blue).

What are the side effects of the mapping biopsy?

Basically, the major side effect is you’re putting a lot of needles in the prostate and it swells. And when it swells up for a few days, you have problems urinating, so that’s why we usually leave a catheter in for 48 hours. The risk of infection is very low. Also, if you’re biopsying outside the prostate, you can actually damage the nerves, so you’ve got to be careful with that. So those are the two big things.

Once the mapping biopsy identifies the location of the cancer, how are the tumor cells destroyed?

So once we know where the cancer cells are, that they’re small, and that we can actually see them and target them, there are a whole bunch of different ways that we can get rid of them. Right now, we’re using freezing, or, cryotherapy. We’re working on other ways, including high-intensity focused ultrasound, electroporation, and more. That to me is not the key. The key is knowing what’s going on, and then you can get rid of the cancer through a number of different ways.

You mentioned that you use cryotherapy in your practice. Can you elaborate on how this treatment works?

With cryotherapy, we’re putting in probes that are 17 gauge or so, which is a little bit larger than the size of the needles we use to take the biopsies. And so what we do is shoot argon gas through these probes, and then at the end there’s a little nozzle where the gas comes through a pinpoint and expands. Well, when argon expands, it’s cold and it freezes, and so you’ve got a way to deliver a gas in through this probe deep into the body and cause an ice ball. And then we also can turn the switches and shoot helium through that needle, and when helium expands, it heats. So we can freeze and heat. We’ve got the balance.

The V-Probe, used with the Cryocare CS System, creates an ice ball ready for delivery.

Has the efficacy and safety of targeted focal therapy been demonstrated through clinical trials?

In prostate cancer you need to follow people for 15 to 20 years. So with all the new treatments, we don’t really know what’s going to happen. What we can say is this: In five years, it looks pretty good. Our failure rates in properly selected patients are just a few percent, and the side effects have been minimal—certainly a lot less than you would expect to see with more aggressive therapies. Patients are maintaining potency and continence. Also, the patient satisfaction has been very high.

How widespread is the use of targeted focal therapy?

It’s growing like wildfire, so to speak. To me, the issue is that a lot of people are kind of just “pretending” they’re doing the procedure. It’s very time-consuming, in that you’ve got to have a good program to do these mapping biopsies. You just don’t go sticking a bunch of needles in the prostate and say, “I got one here and there,” and then not label them “front” or “back” or things like that. It’s also under-reimbursed in that the reimbursement for these mapping biopsies is not real high for the required time commitment. So there are only a few places, I think, that are doing it right, but I think it will get better with time.

For more information, visit www.edavidcrawford.com/drupal/targeted-focal-therapy.

Sources

Barqawi A, Crawford ED. Focal therapy in prostate cancer: future trends. BJU Int. 2005;95(3):273-274.

Barqawi AB, Rove KO, Gholizadeh S, et al. The role of 3-dimensional mapping biopsy in decision making for treatment of apparent early stage prostate cancer. J Urol. 186:80-85, 2011.

Crawford ED, Barqawi A. Targeted focal therapy: a minimally invasive ablation technique for early prostate cancer. Oncol. 21(1):27-32; discussion 33-34, 39.