What’s the best course of treatment for men with localized prostate cancer? That’s actually a trick question: it depends on the individual patient, there are several good choices – and Johns Hopkins urologist Christian Pavlovich, M.D., Director of the Prostate Cancer Active Surveillance Program, is working to expand the range of options even further with a more personalized approach for each patient.
For many men with localized prostate cancer, the first course is to consider active surveillance. Some men can stay on active surveillance forever; their PSA remains low, the Gleason score never changes, and MRI scans show nothing new. For other men, active surveillance provides a much-appreciated breather, several years of careful monitoring before cancer needs to be treated. But for other men, the uncertainty of knowing they have cancer and discomfort of repeated biopsies are more stressful than just going ahead and getting treatment.
Pavlovich hopes to give all of these patients more clarity about the state of their cancer. “The longer we follow men on active surveillance, the more we learn about some of the finer points of monitoring their prostate cancer,” says Pavlovich. In addition to a yearly rectal exam and repeat biopsies every two to five years, men in the Johns Hopkins active surveillance program – more than 1,500 since the program launched – get their PSA checked every six months. That’s a lot of pieces of data being gathered: Pavlovich and colleagues are compiling all of this information to form a much bigger, more intricate picture.
PSA kinetics is the study of the complex variability of PSA over time. “PSA itself is not a good trigger,” Pavlovich says. “Just because it hits 8 or 10 doesn’t mean cancer has progressed. We don’t have a hard and fast PSA threshold, or PSA velocity (rate of change over time) threshold, to trigger recommendations for biopsy or treatment. What has been most predictive in active surveillance is PSA density (PSA divided by prostate volume) and the complex assessment of PSA kinetics.”
Pavlovich and colleagues are working on an “Active Care Tool”, a machine learning algorithm generated from the data of many men in active surveillance who had radical prostatectomy at Hopkins. The Active Care software was developed several years ago, “but we are in the process of refining it. We hope to make it even more helpful and accurate in its predictions for men on active surveillance here, and then to roll it out for other active surveillance cohorts, as well.”
How does it work? Let’s say you are in active surveillance, and have been for several years. All of the data you have generated – from multiple biopsies, results of MRI, PSA tests – can be used to predict what’s happening with your cancer. Do you need another biopsy? The program compares your results with those of other men who have been in active surveillance and ultimately had a prostatectomy. “It’s not just, ‘Your PSA is now 4, it used to be 3,’” says Pavlovich, “but, ‘there’s an approximately 17-percent chance that you are actually harboring more aggressive cancer.’ If we can confirm the accuracy of that prediction, I would like to design a clinical trial using these predictive analytics to guide safer active surveillance.”
Changing up biopsies: Johns Hopkins is one of a growing number of institutions in the U.S. performing transperineal biopsy, reaching the prostate through the perineum (the area of skin between the scrotum and rectum) instead of the rectum. Instead of just repeating the same approach in repeat biopsies, Pavlovich says, there may be an advantage in mixing it up: transrectal biopsy, then two years later, a transperineal biopsy. “We don’t want to miss small, high-grade cancer. Sometimes just changing the route or the direction of the biopsies into the prostate may allow you to find cancers you can’t find another way.”
What about diet? Pavlovich and colleagues are actively looking at whether diet may slow down cancer, but can’t talk about their findings quite yet. “We have more than a decade’s worth of data on men in the program.” In detailed surveys, “patients have reported the variety of food they’ve eaten, and we are looking for nutrients that either promote progression to a higher Gleason grade or prevent it,” by correlating what men eat with whether their cancer progresses or stays the same. “There’s a wealth of data, and it will be coming out over the next six months.” In the meantime, if you are looking for foods that may be beneficial in fighting prostate cancer, check out PCF’s guide, The Science of Living Well, Beyond Cancer, and our blog.
Improving surgery: What about the many men who enroll in active surveillance and ultimately need treatment? For these men, Pavlovich is working to make surgery safer and even less invasive. “My expertise is in extra-peritoneal robotic prostatectomy,” he explains. “I do not operate in the peritoneal cavity at all,” but about a centimeter or two below that, “in the retropubic space, where there’s no risk of abdominal complications.” Many of his surgical patients are at increased risk for complications from abdominal surgery, including men with Crohn’s disease, obesity, previous inguinal hernia repair, other prior major abdominal surgery. “It’s rare to find a completely virgin abdomen in men by age 65.”
For these surgeries, Pavlovich makes the five dime-sized incisions within a very small area for safe removal of the prostate. However, with urologist Mohamad Allaf, M.D., Pavlovich is also performing a “single port” method of robotic prostatectomy, using a new Da Vinci robot that requires only one small incision. “We put the port at the belly button – which is, in fact, just an old scar – and take it out with minimal side effects to patients; we do not have to manipulate the bowels and often, never even see them.” With both robotic approaches, “We are constantly pushing the envelope, trying to make surgery even better, with even fewer side effects.”