Focusing on personalized medicine for prostate cancer at USC Norris

Inderbir Gill has a new tool he takes with him into the operating room these days: A perfect reproduction, the exact size and shape of his patient’s prostate gland, made by a 3-D printer. The 3-D print also shows the exact location of his patient’s cancer, giving him something he has never had before when operating on prostate cancer patients: A guide.

New understanding indicates that surgery may be the best first line of defense for men with aggressive prostate cancer, but the operation is tricky because, once in the abdomen, there is no way for the surgeon to know exactly where the cancer is. Creating a 3-D printed organ is one way the surgeons at the USC Institute of Urology are trying to improve their chances of removing all of the cancer.

“Once we are in there, it has been impossible to see where the cancer is,” says Gill, MD, executive director of the USC Institute of Urology. “Our chances of removing all the cancer increase with better data and better tools.”

Another major advantage of having this type of a tool going into surgery, says Gill, is that it helps him minimize touching certain areas, such as the nerve bundles surrounding the prostate, which is what can lead to incontinence or impotence, both potential side effects from prostate cancer surgery.

Gill has performed only a handful of surgeries using 3-D printed prostates as guides and says the surgeons at the USC Institute of Urology are among the earliest to explore this promising new technology.
But embracing advances in technology, as well as conducting game-changing research, in an effort to improve outcomes for their patients, has always been part of their practice. And these 3-D printed organs are but one of the new tools the team of doctors and researchers at the USC Norris Comprehensive Cancer Center has employed to improve the outcomes for patients.

New focus on dangerous cancer

Until recently, most prostate cancers were considered life threatening. But, new understanding has shed light on the fact that not all prostate cancers are created equal. Some, referred to as high-risk, require aggressive treatment, while prostate cancers of the low-risk variety might only need to be monitored.

“Individualized, risk-adapted treatment of men with prostate cancer is where the focus is,” explains Gill.

But determining who has high-risk cancer and who is at low risk is more difficult than one might think. The standard approach involves needle biopsies taken from 12 samples from the prostate to determine the presence of cancer and the risk profile.

These types of biopsy, because they are unguided, can miss the cancer completely. And because prostate cancer is heterogeneous, meaning patients can have both high and low-risk cancers at once, random sampling might only detect one or the other. New knowledge indicates that the standard biopsy approach over detects low-risk cancer and under detects high-risk cancer.

Given the new focus on finding and treating patients with high-risk prostate cancer, a better detection tool was needed and the team at the USC Institute of Urology, a world leader in the development of novel technologies to improve biopsies, found a way to make them targeted. By fusing two imaging technologies — MRI and ultrasound — they have made it possible to better see areas of the prostate that appear cancerous, which directs the needle only to the suspicious areas.

This new tool, explains Gill, has proven effective in the short time it has been in use at USC Norris. In 90 percent of the cases so far, it has accurately detected high-risk prostate cancer.

Mitchell Gross, MD, PhD, associate professor in the Departments of Medicine and Urology at the Keck School of Medicine of USC, points out that physicians have been wanting better biopsies for years because better biopsies will improve outcomes for their patients.

“USC urologists are very unique in terms of developing that technology and they have created a unique solution to a real problem for patients and physicians,” says Gross. Gross explains that an accurate diagnosis is more important now that there is a growing consensus that it is not necessary to operate on most men with low-risk prostate cancer.

Once in surgery, 3-D printing is not the only new tool robotic surgeons at the Institute of Urology have developed to help them get rid of the cancer while preserving potency and continence functions. They also now incorporate real-time ultrasound imaging during surgery to help more precisely train their tools on the cancerous parts of the prostate.

If they come across a suspicious area around the prostate, they perform an on the spot frozen section biopsy and in 10 minutes find out if more tissue needs to be removed. They also routinely perform extended lymph node dissection in the event the lymph nodes harbor microscopic cancer cells.

At the same time, USC urologists have dramatically reduced recovery time from radical prostatectomy surgery, so much so that even a complicated robotic surgery to eliminate high-risk prostate cancer can now be performed as an outpatient procedure.

Battling high-risk prostate cancer requires high-level research

Even with so many advances on the surgical front, high-risk prostate cancer remains a serious threat to life because it can recur or metastasize. Prostate cancer is the second most common and second most deadly form of cancer for men and recurrent prostate cancer accounts for most of the more than 30,000 who die from prostate cancer every year.

Many patients with high-risk prostate cancer will need some form of systemic therapy to keep the cancer at bay. But choosing the right therapy has been challenging because not all patients respond in the same way.

For the most part, it has been impossible for doctors to predict whether their patient’s cancer was likely to metastasize or if they were going to be one of the cases that responded well to a particular course of treatment.

A team of researchers at USC Norris led by Amir Goldkorn, MD, associate professor of medicine at USC Norris, recently received a grant from the National Cancer Institute to study how prostate cancer patients respond to hormone therapy, which they hope will allow doctors to make better decisions about treatment options for patients with advanced metastatic prostate cancer.

Using white blood cells, primary tumor tissues and circulating tumor cells from prostate cancer patients, they plan to analyze the genes of the androgen pathway, which plays a role in prostate carcinogenesis. The research is aimed at helping physicians predict if a tumor will eventually become resistant to therapy to help them choose the best course of action for a particular patient.

Goldkorn’s laboratory has also been trapping and analyzing circulating tumor cells in the blood to help guide physicians decision-making when it comes to choosing treatments for their patients.

The technology can be used to count the number of circulating tumor cells in a patient’s blood sample, which can help physicians understand if a course of therapy is actually working and if it is not, can help them understand more quickly that their patient may need a different treatment.

“It is a very early indicator if something is working and if it is not,” says Goldkorn. Just as importantly, the circulating tumor cells can be analyzed for the presence of a particular DNA mutation or gene expression, which can help identify the mechanisms driving a patient’s cancer, allowing for more effective treatment of that patient’s cancer.

Several research projects underway focus on understanding the mechanisms that drive metastasis, novel ways to deliver chemotherapy when other forms of treatment have failed, and testing new classes of anti-cancer drugs to name a few. Gill added that he and Gross are collaborating on a research project to try to determine which lesions within the prostate are the ones that will become metastatic based on the genetic profile present within the tumor.

Hoping to stop it before it starts

At any given time there are more than a dozen clinical trials underway at USC Norris on new treatments and even on the prevention of prostate cancer.

Mike Nguyen, MD, MPH, associate professor of clinical urology at the Keck School, has conducted several studies into the prevention of prostate cancer. He is about to begin enrolling subjects in a clinical trial, funded by the National Institutes of Health, to study the use of PROSTVAC as a potential vaccine against prostate cancer.

PROSTVAC activates a man’s immune system against prostate cancer cells, essentially instructing the body’s natural defense system to fight off cancer.

The early results in studies using PROSTVAC in men with metastatic prostate cancer, he says, have been very promising. Nguyen’s study will focus on men with low-risk prostate cancer who opt for monitoring of their cancer, two thirds of whom will receive PROSTVAC and one third of whom will receive a placebo. If successful, PROSTVAC may represent a promising new alternative treatment option for men with prostate cancer.

“This is why patients seek out our team at USC,” says Gill. “We are pushing the envelope on all fronts – making better diagnoses, constantly finessing surgical precision and improving risk-stratification through cutting-edge research.”

by Hope Hamashige