“It became very important to recognize the patient voice in the research process,” said Nelson, who has always blended prostate cancer-focused research with care of prostate cancer patients.
Patient advocates can weigh in on research questions and directions and help educate other patients about the state of prostate cancer research.
“One of my passions is making sure patients and patient advocates are appropriately involved in decision-making. For patients, that’s in terms of decisions about their own treatment. For patient advocates, that’s about research priorities and practices,” said Marty Chakoian, a prostate cancer survivor who heads the PNW Prostate Cancer SPORE patient advocate committee. “I’m really grateful to Pete Nelson and the whole SPORE team for how they have included us.”
Chakoian, who also leads a Seattle-area support group, is enthusiastic about working with his patient advocate colleagues.
“I wouldn’t wish prostate cancer on anyone,” he says, “but mine has introduced me to some pretty wonderful people.”
He and fellow PNW Prostate Cancer SPORE patient advocates meet bi-monthly to learn about (and weigh in on) SPORE projects and their progress.
“Even if a particular project doesn’t apply to me personally, I’m glad to know there are smart researchers working really hard to move treatments forward,” Chakoian said.
This includes early-career investigators who are laying the foundation of their research careers. By offering funding for new prostate cancer researchers and novel pilot projects, SPORE grants help build cancer research’s next generation of scientists.
This allows the SPORE to support more than its official four projects, and allows research to grow in creative new directions.
“The SPORE keeps breeding more science,” said Fred Hutch and UW medical oncologist Jessica Hawley, MD, MS
Once an institution secures a SPORE, it can’t rest on its laurels: Every five years, a SPORE must report impressive progress to secure the next five years of funding. Only projects that make progress toward the clinic get carried forward; those that don’t pan out are replaced by promising new ideas.
PNW Prostate Cancer SPORE
Only SPORE centers with a consistent track record of excellence get renewed. The PNW Prostate Cancer SPORE has been continuously funded since its inception in 1999.
“At that point in time, there probably wasn’t a single therapy shown to help men [with advanced prostate cancer] live longer, other than testosterone suppression,” Nelson said. “That was the standard of care — and still is — for more than 70 years. But other than that, there were no life-prolonging treatments [for metastatic cancer]. So it was a pretty desperate time.”
On top of this, advanced tumors can evolve ways to resist treatments that lower androgens, requiring new approaches to halt prostate cancer growth. These are termed metastatic, “castration-resistant” prostate tumors.
To improve prognosis, understand treatment resistance and develop new therapies, scientists needed a deeper understanding of prostate cancer biology. The first SPORE projects focused on identifying the molecules that influenced the risk of developing prostate cancer, drove prostate cancer progression, shaped its responses to treatment and distinguished different prostate cancer subtypes.
“The success of the PNW Prostate Cancer SPORE is due in a large part to the vision of the original principal investigators,” Nelson said.
UW urologist Paul Lange, MD, now Chair Emeritus of UW’s Department of Urology, and Fred Hutch epidemiologist and professor emerita Janet Stanford, PhD, MPH, recognized how important collaboration would be to leverage the different strengths of the research institutions in the Pacific Northwest.
“Thanks to their foundation and foresight, we remain on the leading edge of translationally focused prostate cancer research,” Nelson said. “It’s more powerful to collaborate: Having the manpower, the resources, and the ideas from many investigators lets you innovate and promote the most impactful research and treatment.”
From the beginning, the international team spread a wide scientific net.
“Prostate cancer can be tackled from many perspectives, including prevention, understanding risk, improving screening and developing new therapies,” Nelson said. “There’s enough expertise in the PNW Prostate Cancer SPORE to cover a very wide swath of research.”
Transforming patient care
The deep understanding of prostate cancer biology made possible by the SPORE’s international team has changed treatment guidelines. These insights ushered in more targeted treatments and helped oncologists begin to understand how prostate tumors evolve to resist treatment.
In 2016, Nelson and SPORE collaborators Heather Cheng, MD, PhD, and Colin Pritchard, MD, PhD, showed that men with advanced prostate cancer were five times more likely than men in the general population to have inherited mutations in DNA-repair genes like BRCA1 and BRCA2.
The finding was unexpected, but transformative for patients and their families.
It highlighted the role that inherited mutations may play in cancer development and the importance of genetic screening for prostate cancer patients and their family members. A patient’s siblings may also have inherited the same mutation, and they may have passed it to their own children. If a man tests positive for such a mutation, his family members have critical information they can use to assess their own risk. If they also test positive, the family members can opt for more aggressive screening strategies designed to catch prostate (and breast, ovarian and pancreatic) cancers early.
To improve genetic screening for men with advanced prostate cancer, Cheng, with UW colleague Bruce Montgomery, MD, initiated the GENTleMEN study (GENetic Testing for MEN with prostate cancer).
“[We set up this study] to remove barriers and improve access [to genetic testing and precision oncology] throughout the state of Washington,”Cheng said of the five-year study, which began in 2017.
The study offered men with metastatic prostate cancer an internet-based way to access genetic testing. Participants who tested positive for certain inherited mutations had access to genetic counseling through Fred Hutch and could share their results with their family members and oncologists.
Cheng and the team demonstrated that their approach connected men to important genetic testing, and identified strategies that could help make the approach more feasible for more prostate cancer patients.
By 2020, the National Comprehensive Cancer Network (NCCN) guidelines incorporated new recommendations: that oncologists offer genetic testing to men with metastatic, lymph node-positive, or high-risk localized prostate cancer.
They followed GENTleMEN with the GIFTS (Genetic Information to Inform Treatment and Screening) study. GIFTS drew on Stanford’s studies of inherited prostate cancer, and the NCI’s Surveillance, Epidemiology, and End Results registry to proactively identify men in Washington state who might benefit from genetic testing.
But their initial results were “sobering,” Cheng said.
They found that only 11% of people contacted were receiving the genetic testing recommended by the NCCN. The SPORE team increased that to 44% by mailing men saliva testing kits and a questionnaire about their family history and knowledge of genetics. GIFTS also helped them better understand which barriers to obtaining NCCN-recommended testing.
Such genetic testing can also help improve treatment for men with these mutations.
“This project led us to understand that some prostate cancers are very vulnerable to certain types of drugs that are involved in DNA repair,” Nelson said. “The clinical tests that identify which patients would benefit from platinum-based drugs and PARP inhibitors were developed through SPORE-supported research.”
Use of these drugs result in DNA damage that cells with defective DNA-repair enzymes can’t overcome. The SPORE’s findings provided a biological explanation for why some men’s tumors responded to these therapies, and made it possible to better identify patients whose tumors are most likely to respond. In 2020, the first PARP inhibitor was approved to treat metastatic prostate cancer that’s resistant to androgen-suppressing drugs.
“Another major outcome of PNW Prostate Cancer SPORE research involved contributions to the understanding of androgen metabolism,” Nelson said. “Multiple drugs were built on foundational work in understanding the signaling of the androgen receptor.”
These include the modern crop of androgen receptor-targeting drugs, like abiraterone and enzalutamide, that have dramatically extended life expectancy for men with advanced prostate cancer.
