This story was published in the May 2024 issue of the Breakthroughs newsletter.

Prostate cancer is the most common type of cancer in men and is currently the second-leading cause of death in men in the U.S. About one in eight men will be diagnosed with prostate cancer during their lifetimes, according to the Centers for Disease Control and Prevention. In 2023, an estimated 288,000 new cases of prostate cancer were diagnosed along with more than 34,700 related deaths, according to the National Cancer Institute.  

These statistics can be staggering and reinforce the importance of the National Cancer Institute establishing seven Specialized Programs of Research Excellence (SPORE) in prostate cancer across the U.S. beginning in 2001, one of which includes the Robert H. Lurie Comprehensive Cancer Center of Northwestern University’s Prostate Cancer SPORE. 

The goal of the Lurie Cancer Center’s Prostate Cancer SPORE is to advance translational research across the bench and bedside including clinical trials developed and led by scientists at Northwestern, in collaboration with the University of Chicago Comprehensive Cancer Center and the NorthShore University HealthSystem, that aim to improve outcomes and quality of life for patients with prostate cancer. 

Currently co-led by Sarki Abdulkadir, MD, PhD, the John T. Grayhack, MD, Professor of Urological Research and vice chair for Research in the Department of Urology, and Maha Hussain, MD, the Genevieve E. Teuton Professor of Medicine, the Prostate Cancer SPORE has more than 70 Northwestern faculty members. Every SPORE research project is co-led by a basic scientist and a clinician to ensure the development and execution of bench-to-bedside research.  

Patient survival is heavily dependent on early detection and tumor grade. Localized prostate cancer (no indication that the cancer has spread outside the prostate) and regional prostate cancer (when the cancer has spread outside the prostate to nearby areas or lymph nodes) have a five-year survival rate of 99 percent. Metastatic disease survival has improved over the past 20 years, but it continues to be deadly with an average survival rate of about six years. Prostate cancer also disproportionally affects Black men compared to other racial and ethnic populations. Because of these differences between local and regional cancer compared to metastatic disease survival rates, as well as racial disparities, the research takes on urgency.  

“The overarching mission of the SPORE is to accelerate and facilitate research to be translated to benefit patients, whether it’s in diagnostics, therapeutics or prevention,” Abdulkadir said. 

In 2021, the SPORE received a $9.2 million grant renewal from the National Cancer Institute to focus on two high-interest research areas in the field: targeting the MYC pathway, a well-characterized oncogenic transcription factor in prostate cancer, and redirecting the sensitivity of metastatic castration-resistant prostate cancer to immunotherapy.  

Additional areas of interest, according to Abdulkadir, include distinguishing whether early-stage cancer will progress and become aggressive, which account for nearly one in five prostate cancer cases. 

“Figuring out which ones that will go on to be aggressive is important because then you can treat those patients more aggressively, and for the ones that will not likely be aggressive, you can spare the patients treatment because, whether it’s surgery or radiation, could have side effects for some patients,” Abdulkadir said.  

Advancing the Science  

Other key aspects of the SPORE’s research are identifying treatments to treat patients with recurrent disease and determining which patients will respond to the treatment or develop treatment resistance.  

Abdukadir’s recent study published in Nature Communications found that increased expression of specific genes, including the MYC signaling pathway, in patients with prostate cancer may predict whether the cancer will respond well to hormone therapy, which suppresses the production of testosterone. These results pave the way for predicting which prostate cancer patients will respond well to hormone therapy, a future research direction in the Abdulkadir laboratory, 

In the largest-ever study of its kind, a team of investigators including co-author William Catalona, MD, professor of Urology, linked mutations in 11 genes to aggressive prostate cancer, recently published in JAMA Oncology. These findings may help providers identify high-risk patients and treat them more effectively.  

“There’s a lot of interest in trying to find newer ways to treat patients with new drugs and treatments, and actually some of our SPORE projects are looking at different pathways that don’t have drugs that can target them,” Abdulkadir said.  

Pursuing Drug Trials 

Personalized medicine will also help move the needle forward for prostate cancer treatment efficacy, Abdulkadir said. For example, a recent study led by Maha Hussain, MD, found that men with hormone-resistant prostate cancer and BRCA genetic mutations who were treated with the PARP inhibitor drug, olaparib, survived longer than men treated with traditional hormone therapy.  

Because of these findings, and other recent advances in prostate cancer treatments, survival has increased. Therefore, new criteria are needed to measure overall survival in prostate cancer clinical trials, Hussain argued in a separate meta-analysis published in the Journal of Clinical Oncology.  

“Essentially, the bottom line is: both radiographic progression-free survival and progression-free survival can potentially be used as an endpoint because they are strong surrogates for overall survival,” Hussain said. 

Combination treatments may also be a promising approach. A recent study published in Nature Medicine, in collaboration with Ashley Ross, MD, PhD, associate professor of Urology, found that men with high-risk prostate cancer who received immunotherapy treatment with the monoclonal antibody enoblituzumab in the weeks leading up to surgery had favorable rates of disease remission and tumor downgrading after surgery.  

Assessing Biopsy Risk 

Other research from SPORE members have compared infection rates in prostate cancer biopsy approaches. Work led by Edward Schaeffer, MD, PhD, chair and the Harold Binstein Professor of Urology and published in the journal European Urology, found that post-biopsy infection was reported in four patients in the transrectal biopsy group and zero patients in the transperineal biopsy group. Patients who did develop an infection took oral antibiotics or had a brief hospitalization but were not admitted to the ICU and did not develop sepsis. 

Additionally, investigators led by Adam B Murphy, MD, MBA, ‘14 MS, ‘10 GME, the Distinguished Professor of Health Equity Research in Urology, developed a prostate biopsy risk calculator in Black men to improve biopsy decision-making and outcomes compared to current tools developed in non-Black populations.  

As the field moves forward, so do the SPORE’s objectives. During the SPORE’s past grant renewal cycles, SPORE members have come together to solicit new research projects, receive constructive feedback and work with SPORE leadership to deploy new projects.  

With the SPORE’s current grant cycle ending in 2026, Abdulkadir said he is looking forward to going back to the drawing board with his colleagues.  

“It’s always an exciting time when we do this because we see a lot of very innovative research that’s happening across the board and across the campuses. It’s really exciting to see what people come up with to move the field forward,” Abdulkadir said.