Allaf: If the trial proves successful, "this potentially ushers in a new era of surgery that's molecularly based."

Molecular-directed prostatectomy, refinements in control of urinary continence, and a comparison of prostate biopsy approaches: clinical trials that will shape prostate cancer diagnosis and treatment.

Important clinical trials related to prostate cancer are under way at the Brady, and urologist Mohamad Allaf, M.D., the Jakurski Family Director and Urologist-in-Chief, is helping lead them. “Trials are really what inform clinical care,” says Allaf, “but surgeons don’t perform a lot of clinical trials. In fact, clinical trials in urology are rare – and these are all potentially practice-changing.” Two of the trials are related to the nerve-sparing radical prostatectomy procedure, developed at the Brady by Patrick Walsh, M.D., and a third is a comparison of two forms of prostate biopsy.

Looking for stray cancer cells with a PSMA tracer: PSMA tracing is, on a molecular level, basically like using a black light to make colors glow – and what lights up is prostate cancer. PSMA (prostate-specific membrane antigen) is a protein that sits on the surface of prostate cancer cells. Hopkins physician-scientist Martin Pomper, M.D., Ph.D., and colleagues figured out how to target it using a small molecule attached to a radioactive tracer, and this molecule was FDA-approved for PSMA-PET imaging.

Now, building on this technology, Intuitive Surgical (the company that makes the DaVinci device used in robotic prostatectomy) is sponsoring a Phase II clinical trial to see whether a PSMA-targeting agent can make a difference in prostatectomy. Hopkins is one of four centers participating in the trial, along with UCSF, Memorial Sloan-Kettering, and the Mayo Clinic.

“The agent is injected the day before surgery,” says Allaf, “and then we can turn on an infrared camera during surgery, and we’re able to see the fluorescence. The cancer appears green on the screen.” If the trial proves successful, “this potentially ushers in a new era of surgery that’s molecularly based. We’re able to see the tissue as we normally do during surgery, and also to discern something about it molecularly.”

At each step in surgery, “we turn on the infrared camera, and if we see the green, not only can we react to it and cut wider, but we mark the tissue with ink,” so pathologists can double-check the results of the tracer.

Allaf has side-by-side pictures of the same prostate taken during surgery. There is a tiny dot of green. “It’s just a little thing, but that’s how a recurrence starts.” In this case, the green was in tissue that was already earmarked for removal. “But if it had not been, we would have taken it out.”

Optimizing the recovery of urinary continence: One of the most significant consequences of radical prostatectomy is the temporary loss of urinary control. This happens because the urethra, the tube that carries urine from the bladder out of the penis, runs through the prostate, and must be cut and then reattached after the prostate is removed. In an NIH-funded, multicenter clinical trial just getting started, prostatectomy patients will be randomly assigned to one of two slightly different surgical approaches to preserving urinary continence during robotic prostatectomy, and then followed for a year.

Which biopsy is better? In another NIH-funded clinical trial, which has just ended, “biopsy-naïve” men (who have never had a prostate biopsy) were randomly assigned either to undergo the traditional transrectal biopsy, which reaches the prostate through the rectum, or the transperineal biopsy, which goes through the perineum (the area of skin between the scrotum and rectum). Allaf is one of the Principal Investigators, along with Brady alumni Edward “Ted” Schaeffer, M.D., Ph.D., now at Northwestern, and Jim Hu, M.D., M.P.H., now at Cornell.

“Which form of biopsy is better? That’s a big question today, given that over one million prostate biopsies are performed a year in the U.S.,” says Allaf. The investigators found that the rate of cancer detection between the two approaches was the same. However, the risk of infection was not: close to 2 percent in the transrectal biopsy group “despite antibiotics and a rectal swab,” versus 0 percent in the transperineal group. The study’s results are being submitted for publication.

To find out more about clinical trials at the Brady, please go to clinicaltrials.gov. Note: Look for trials of “prostatic neoplasms.”