Killing the Cancer, Not the Prostate
Focal therapy, although not the standard of care, is emerging as a way to treat localized prostate cancer in carefully selected patients. I recently interviewed one of the leaders in this field, urologist Arvin K. George, M.D., Director of Prostate Cancer Programs at the Brady Urological Institute at Johns Hopkins.
Focal treatment is just one part of George’s clinical practice, which spans the diagnosis and management of prostate cancer and other genitourinary cancers; he is an expert surgeon who performs robotic prostatectomy and kidney surgery. His research focuses on the use of imaging and biomarkers in diagnosis, risk stratification, and management of prostate cancer.
Why is focal therapy a tricky subject? As we have discussed here and elsewhere on this website and in the book, Prostate cancer is a multifocal disease: like dandelions in a field, cancer can spring up in several places within the prostate at the same time. That is why the gold standard for localized disease is to treat the entire prostate through surgery or radiation.
Focal therapy – killing, or ablating, only the known spot or spots of clinically significant cancer within the prostate – has been around for decades in various forms; the most common approaches are cryo (freezing) therapy and high-intensity focused ultrasound (HIFU), and other technologies are emerging. But for years, urologists have had questions about the idea of focal therapy itself, including:
- What if you kill cancer in one spot, but miss another tiny site or sites of cancer?
- Urine exits the body through the urethra, which runs right through the prostate, like a road through a tunnel. To protect it during focal therapy, doctors maintain its normal temperature with either a heating or cooling tube. What if there is cancer near the urethra that is also spared?
- What if one spot of cancer is ablated, but a new one starts to grow? Can the prostate tolerate multiple courses of the same type of focal therapy, should a different approach be used, or should the patient shift to surgery or radiation?
Why is Johns Hopkins now investigating and offering focal therapy? What has changed?
First and foremost, says George, the reason is imaging. “The better imaging gets, the better and more precise our treatments become.” Improvements in MRI have been game-changing. “We can see where a lesion is, how far it extends, and apply a treatment to just that area.” That’s true, although some cancers just don’t show up on MRI, as discussed here. There is also a potential for PSMA-imaging technology to play a role in the treatment of localized disease, although so far it has not routinely been used in patients who are considering focal therapy. PSMA-PET is more of a “big gun” brought out when it’s suspected that cancer has escaped the prostate.
Risk stratification has gotten a lot better, too. PSA density, second-line biomarker tests like the 4K score and Prostate Health Index (PHI,) and molecular pathology findings (from the biopsy tissue) help doctors create a “profile” of the cancer, to evaluate its potential to be aggressive or more slow-growing.
Thus, says Mohamad Allaf, M.D., Director of the Brady Urological Institute (and, incidentally, the Hopkins surgeon who took out my husband’s prostate and saved his life, thank God!), “as we are understanding the biology of the disease more and our ability to see the cancer has gotten better – even though MRI and PSMA-PET aren’t perfect – there may be a role for focal therapy.” This remains to be proven, he adds, and “Arvin is perfectly suited to doing this. Doctors out in the community are already providing focal therapy, and somebody needs to take the lead to study it in a very rigorous way, tracking the cancer control long-term. We see the Brady as a steward of treatment and as a leader in defining the role of focal therapy. The unique thing Arvin brings is the academic rigor to study and implement focal therapy and anything image-guided within prostate cancer, including new MRI fusion transperineal biopsies.”
“We Definitely Have Some Bridges to Rebuild”
One important priority is improving the public understanding of focal therapy, says George. “We definitely have some bridges to rebuild,” because of physicians worldwide over the last 20 years who have not been as responsible or, regrettably, as skillful as they should have been. “We didn’t know what we didn’t know. There was a learning curve to this new technology: how we apply it, and how we follow men afterwards. We have some clarity regarding this with updated surveillance protocols, but we still have much to learn!”
That said, he adds: “Some practitioners of focal therapy out there have been frankly sketchy,” he says, “providing inadequate coverage of the cancer, exorbitant out-of-pocket costs, no follow-up, learning on patients as the technology developed, causing fistulas and other complications. We are still suffering from that hangover of offshore treatments and cash pay.”
But focal therapy is not the same today as it was then. With rigorous follow-up, George says, focal therapy can be a good option for some men with localized cancer. “Tens of thousands of cases of focal ablation have been performed,” he says. “While we have less data than that, we do have five- to seven-year median outcomes on more than 1,300 patients that have been published.” He believes focal therapy is here to stay. “It’s all about choosing the right patient.”
Right now, the “sweet spot” for focal therapy, as we discussed here, is a patient with favorable intermediate risk. “Less aggressive cancer may require no treatment at all, and more aggressive disease requires more aggressive treatment.” The ideal patient “has cancer that is visible on imaging but is not near vital structures like the urethra, rectum, or neurovascular bundles, and has no high-risk features such as extracapsular extension or seminal vesicle invasion.”
George is the Principal Investigator of two clinical trials of focal therapy. One is the PRESERVE study, involving prostate tissue ablation through irreversible electroporation (IRE). IRE is largely “athermal.” It doesn’t use either heat or cold; instead, it generates an electrical field across tissues between two electrodes. The electricity creates holes in the cells on a microscopic level, causing them to die. “Because IRE doesn’t harm the scaffolding, or connective tissue, theoretically, it can treat closer to the nerves.” The other study is the VAPOR 2 trial, using water vapor to destroy tissue. “This is an extremely hopeful time for men with prostate cancer.”
In addition to the book, I have written about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” I firmly believe that knowledge is power. Saving your life may start with you going to the doctor and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.
©Janet Farrar Worthington