Focal Therapy for Localized Prostate Cancer, Part 2

            Is focal therapy for every man with localized prostate cancer?  Absolutely not.  In fact, says Northwestern University urologic surgeon Ashley Ross, M.D., Ph.D., it’s not even a good option for the majority of patients.  But for a few carefully selected men, with close follow-up, “it can be a curative option with minimal side effects.”

Ross, one of the leaders in the developing field of focal therapy, is the expert I interviewed for the 5^th edition of our book –where we not only talk about focal therapy for localized prostate cancer; we devote a whole chapter to it!   This is a significant milestone, especially if you look at all the previous editions of our books dating back to 1993, where we basically offered zero encouragement for taking this approach.

But – but – focal therapy is out there!  It is here to stay!  It’s available all over the world!  Yes, that’s true.  Does it work long-term?  Nobody knows yet.  The current National Comprehensive Care Network (NCCN) guidelines state that “cryotherapy or other local therapies are not recommended as routine primary therapy for localized prostate cancer, due to lack of long-term data comparing these treatments to radical prostatectomy or radiation.”  Also, except for follow-up biopsy, there is no way to prove cure with focal therapy.  PSA does not become undetectable because much of the prostate is still untouched, and that prostate tissue is still making PSA.

This is why long-term follow-up is critical:  you have to keep watching the PSA, and if it changes, you need a repeat MRI.  So, no matter what anyone says, focal therapy is not the standard of care; it is still considered investigational.

The last post (part 1 of this series) was devoted to all the reasons why men interested in this approach should proceed with a whole lot of caution.  This post starts to look at who might consider focal therapy.

            Why am I talking about it now?  What has changed?  Imaging, for one thing; prostate MRI and targeted MRI fusion (also called mpMRI) biopsies.  Also, there are intelligent blood and urine tests that can help determine whether a cancer is clinically significant (we have updated information on this in the 5^th edition of the book).

Taken together, maybe with genetic testing if there’s a strong family history of cancer, it is possible to get a decent idea of the kind of cancer you’re dealing with.  You can’t just say, oh, I have localized cancer!  You need a more nuanced understanding of this cancer, and that requires putting together every available piece of information you can get.  Don’t just put all your faith in the biopsy.  Remember, a biopsy only looks at 1/10,000^th of the prostate.  Yes, that’s one ten-thousandth.  Not a lot of tissue!  Just because the biopsy says Gleason 6 doesn’t mean there’s not some higher-grade cancer in your prostate; many men are “upstaged,” that is, a higher grade of cancer is found after prostatectomy when the pathologist examines the removed prostate tissue.

And don’t put all your faith in the MRI.  As good as MRI is, some prostate cancers still don’t show up on it; they’re spread out, like plankton on the ocean, instead of all knotted up in one dense ball.  But if you put the imaging, the biopsy, and the other tests together, you can get a pretty good handle on the kind of cancer you have.

            Do you have the kind of cancer that needs to be treated right away?  If not, active surveillance is a great initial option.  It buys you time and has zero side effects.  If you have Gleason 3+3 (low-risk or very low-risk) or 3+4 (favorable intermediate-risk cancer), with not a lot of pattern 4, and the cancer seems safely contained within the prostate, then be thankful!  You have some breathing room.  Plenty of time to make a treatment decision when and if your cancer needs to be treated.

            If you have localized cancer but there’s a lot of Gleason pattern 4, or any Gleason pattern 5, (4+3=7, 4+4=8, 4+5, 5+4 or 5+5), then you have cancer that is not only clinically significant, but likely to spread, and the prostate needs to go – either with surgery or radiation, and if it’s higher-grade, higher-volume, and close to the borders of the prostate and you are deemed at high risk, you may need to escalate with a temporary course of hormonal therapy, as well.   We discuss all of these scenarios in detail in the book.

Who is the Ideal Candidate for Focal Therapy?

            Ross believes there is a “sweet spot” for focal therapy:  men with high-volume low-risk disease (Gleason 3+3) and favorable intermediate-risk prostate cancer (a little bit of Gleason pattern 4), “provided their disease is localized to one area of the prostate,” he says.  Preferably with just one lesion and ideally, “a lesion that is more anterior (above the urethra), as that allows for sparing of the neurovascular bundle.”

            Ideal candidates for focal therapy, he continues, should have a life expectancy of 10 years or greater.  They should be willing and able to undergo an MRI and biopsy, or should consider a saturation biopsy to make sure there aren’t areas of higher-grade cancer lurking in the prostate.  “Men also have to be willing, in my opinion, to undergo a confirmatory biopsy,” to make sure the focal treatment worked.  “They must have a very low chance of lymph node involvement, because obviously you’re not going to treat with focal therapy a disease that has spread to the pelvis.”

            The bullet points here:

• 10-year or higher life expectancy
• Unilateral cancer (one area, or focus), preferably away from the neurovascular bundles on both sides. A man who has multifocal disease (several bits of cancer sprouting simultaneously within the prostate; like seeds on a strawberry) “has a higher propensity for developing more prostate cancers,” and should not be considered for focal therapy.
• You need a follow-up biopsy to make sure you’ve been cured.
• Also, says Ross, you should undergo genetic testing if recommended. In the book, Ross mentions two kinds of genetic tests:  one looks for mutations in genes such as BRCA2, which raise the risk of developing aggressive cancer.  “Patients with genetic risks are potentially poor candidates for focal therapy,” says Ross.   There’s another kind of genetic test: one that looks for multiple genetic variations that are known to raise the risk of getting prostate cancer.  These are not mutated genes, but mutated sequences of DNA.  Men with high polygenic risk scores are more likely to have multifocal disease, and “also may be poor candidates for focal therapy.”

            Here is a case study Ross presented at Northwestern, which we used in the book.

            “Daniel” is 74, with a PSA of 7.1  No cancer was felt on his rectal exam, but an MRI showed one lesion, with a PI-RADS score of 5, in the right transitional zone.  His MRI-targeted prostate biopsy found cancer, Gleason 3+4=7 – but not much of it.  Cancer was only found in three out of 12 cores of the biopsy, but in two of those cores, 40 percent of the cancer was Gleason pattern 4.

            Daniel is still working and fairly active.  Ross estimates his life expectancy to be around 10 years.  Daniel has some health issues, including atrial fibrillation, and is on a blood-thinning drug, Eliquis.  Before coming to see Ross, he met with another urologist to discuss robotic prostatectomy, and with a radiation oncologist.  “He wasn’t interested in radiation therapy,” says Ross.  “He was worried about bleeding episodes” because of the Eliquis.  “He also worried about surgery.”

            Daniel underwent cryoablation, killing cancer cells with extreme cold – creating an “ice ball” of tissue, which then dies).  This focal procedure spared both neurovascular bundles (the nerves on either side of the prostate that are responsible for erection) and, because of the location of the tumor, did not affect the urethral sphincter.  It was done as an outpatient procedure, and Daniel went home the same day.  “He had an uneventful recovery, had immediate continence, which was complete, when the catheter was removed in seven days.  He had no decline in sexual function,” although Daniel had already experienced some ED before the procedure.  Three months later, Daniel’s PSA dropped to 0.94.  “We will continue PSA monitoring, and have an MRI and confirmatory biopsy at 12 months.”

            Part 3 of this series will be my interview with Johns Hopkins urologist Arvin George, M.D., who is investigating several different types of focal therapy and believes this treatment is going to be helpful for a wider window of patients.

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