Dr. Jim Hu is a urologic oncologist at Weill Cornell Medical College, where he serves as the Director of the LeFrak Center for Robotic Surgery and the Ronald P. Lynch Chair in Urologic Oncology.
Prostatepedia spoke with him about a focal therapy clinical trial that he’s running.
What is the context for your clinical trial?
Dr. Hu: If you look at breast cancer surgery about 40 years ago, for instance, some of the trials were done to demonstrate that a lumpectomy or a partial mastectomy in many cases was as good as removing the breast entirely. In prostate cancer, focal therapy or partial gland ablation is referred to often as the male lumpectomy.
The challenge for why there hasn’t been a partial gland approach with prostate cancer is the timeline of knowing differences in outcomes. If you took a whole gland versus a partial gland approach, you’re not going to see it as quickly as you might in breast cancer, where metastasis or death can occur in a shorter time. In prostate cancer, 95 percent of men who are diagnosed are still alive 10 years after their diagnosis.
In about 75 percent of men who are diagnosed, prostate cancer is multifocal, so even if on a biopsy you find it in one area, it’s not uncommon that when prostate is removed surgically, the pathologist detects prostate cancer in multiple areas. That’s also been a barrier to the use of partial gland treatments in prostate cancer, and multifocality is less common in breast cancer.
When you’re treated for prostate cancer, the blood test biomarker to determine whether you’re free of cancer is the prostate-specific androgen (PSA). In contrast to other cancers, when you’re treated for localized disease for instance, you don’t do CAT scans or X-rays to see if something has grown back or spread because the PSA is going to become detectable before there’s any radiographic signs of a recurrence. Therefore, if you only treat part of the prostate, the part that’s untreated, the normal prostate is going to continue to produce PSA. Therefore, the PSA is not going to be a meaningful marker of cancer recurrence with partial gland ablation. There are many unknowns in terms of how we should follow these patients who have partial gland ablation approaches.
What has driven the greater interest or the increased realization of partial gland ablations? MRIs are done commonly in the United States when men have an elevated PSA as a biomarker or as a predictive test beyond an elevated PSA of what the biopsy may show. This may help them forego a biopsy, but MRI’s increased sensitivity or accuracy for finding significant cancers is about 70-80%.
Fusion-guided platforms take the MRI and fuse them to the ultrasound, which allows us to better pinpoint where the suspicious area is within the prostate. These fusion-guided platforms have enabled a more accurate diagnosis within the prostate. This has led to the application of these MRI ultrasound fusion platforms to deliver energy to kill cancer cells that have been confirmed in those areas. In other countries around the world, there has been availability of one of the partial gland approaches, high-intensity focused ultrasound (HIFU).
Before 2015, when the FDA approved HIFU for treating prostate cancer in this country, it was pretty common for men who were seeking partial gland treatments to fly overseas and pay out-of-pocket for these treatments.
We know that HIFU kills prostate tissue, but we don’t know what the outcomes are for prostate cancer, and therefore, the FDA has not given a prostate cancer indication. You can’t market it as treating prostate cancer, and because of the absence of comparative data to other treatments, Centers for Medicare & Medicaid Services (CMS) will not reimburse the full amount for prostate cancer treatment currently.
Other insurances follow the lead of CMS. It’s an interesting time. There is a need for comparative effectiveness research for clinical trials that compare this new treatment option of partial gland ablation to established methods of surgery, radiation, or active surveillance.
What can patients expect to happen in the trial?
Dr. Hu: In our trial, you have an MRI and a biopsy within 6 to 12 months after you get partial prostate gland ablation. There may be a tendency for people to get treated and never come back, assuming that the treatment was successful. This would almost be like receiving a placebo and not wanting to receive bad news if cancer returns.
Typically, a clinical trial means that we’re offering a treatment to a patient. We don’t really know the long-term outcomes. Therefore, there is a defined follow-up. Participants agree to get treated so that we can study this and clear up some of the uncertainty for others in the future, and so that we can detect a cancer recurrence earlier with structured follow-up. Data and outcomes are tracked as they occur, or prospectively to ensure complete collection of outcomes. We want a control group in which the patients get standard treatment and we want an experimental or an intervention group who receives the new or novel treatment. This balances differences in characteristics such as age, race, other medical issues such as diabetes, cancer characteristics, etc.
The challenge with trials in prostate cancer is that few men would agree to having their fate based on randomization. If we said to your average American man with prostate cancer that we’ll flip a coin, and if it’s heads, you’ll receive partial gland ablation, and if it’s tails, you’ll get surgery, they wouldn’t go for it.
This is reinforced by 11 randomized trials in localized prostate cancer that have failed to recruit. In this case, its also a bit of comparing apples to oranges in the sense you’re comparing treating part versus treating the entire prostate. Therefore, the side effect profiles are different in terms of incontinence, erectile dysfunction, and so forth.
It’s a space that needs more studies because there are many men who are interested in this technique.
One of the unfortunate aspects with men travelling overseas for HIFU is that we don’t know what they’re getting. We know of instances in the United States where practitioners are marketing a laser approach to prostate cancer, and men are paying $25,000 out-of-pocket, but there are too many unknowns.
Another example is laser treatments of prostate cancer which are advertised online or on billboards. These need to be studied thoroughly. Unfortunately, the out-of-pocket nature of non-coverage by insurance distorts incentives with out-of-pocket payments for new technologies that are unproven and may not be studied thoroughly in that fee-for-service environment.