Innovations in cancer treatments start with discoveries in the laboratory – which is where Fox Chase Cancer Center has made powerful inroads for more than 100 years to advance care for patients in the local community and throughout the world.
Bladder cancer is among the 10 most common cancers worldwide, and it develops in men at rates three times higher than in women. Through the groundbreaking discoveries of Dr. Philip Abbosh and Dr. Elizabeth Plimack, whose research focuses on bladder cancer and other genitourinary cancers, many patients have gained access to emerging therapies that include novel ways to preserve the bladder and maintain quality of life.
Dr. Abbosh, Assistant Professor in the Nuclear Dynamics and Cancer program at Fox Chase, leads a research lab with projects that focus on achieving no residual disease states in patients with localized bladder cancers and then accurately identifying those patients. Dr. Plimack, Deputy Director of Fox Chase and Professor in the Department of Hematology/Oncology, is internationally recognized for her expertise in genitourinary cancers and her leadership in clinical trial design and implementation. Collectively, these two pioneers are uncovering and leveraging new scientific solutions that drive more meaningful clinical care for cancer.
A notable and collaborative research project involving Drs. Abbosh and Plimack is the Fox Chase-directed RETAIN BLADDER trials, which have aimed to identify whether certain muscle-invasive bladder cancer patients could ultimately keep their bladder. Currently, standard of care is to treat patients with preoperative chemotherapy and then perform a cystectomy, surgically removing the bladder.
Researchers had previously tested different chemotherapy regimens and collected tissue from patients during early trials that began in 2009. They found that about 40 percent of the bladders that were removed had no cancer, and that the tissue presented certain clues regarding what types of tumors might be eradicated by chemotherapy and which would require surgery as well. Those markers were then applied to the RETAIN trials, in which patients with tumors that harbored markers of a likely successful response to chemotherapy were treated with the goal of keeping the bladder intact.
For some bladder cancer patients, the chemotherapy succeeds in wiping out the cancer and might prevent the need for a cystectomy, which necessitates a significant change in everyday life. The key is identifying who those patients are. Early work led by Dr. Plimack identified a set of genomic biomarkers that can help select patients for bladder preservation.
This finding was leveraged into a series of clinical trials. The endpoint was metastasis-free survival after two years.
At the two-year endpoint, almost half (46 percent) of the 26 patients in the active surveillance group had survived while retaining their bladders. However, 10 out of 26 (38 percent) active surveillance patients developed metastatic disease. The two-year metastasis-free survival rate was 77 percent.
Dr. Plimack, a co-author of the study, says: “Our question as we look at these data is this: Would earlier cystectomy have cured the 10 patients in the observation cohort who later developed metastatic disease? And if so, how can we better discover who they are to route them to earlier surgery while sparing cystectomy for those who can safely keep their bladders?”
A key discovery was that when active surveillance participants developed recurrent localized disease in their bladder, it was a good indicator that it was time to remove the bladder rather than continue with local therapies. Of the 10 active surveillance patients who developed metastatic disease, 90 percent recurred with localized disease first.
These results, presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium, informed the subsequent trials in which patients receive an initial combination of chemotherapy and immunotherapy, instead of chemotherapy alone. The research team is studying whether this combination better eradicates the cancer and improves two-year metastasis-free survival in patients who retain their bladder.
“We would obviously not want to miss an opportunity to cure a patient with a big surgery, but we also don’t want to do surgeries that patients might not need, even if the outcomes are excellent,” says Dr. Abbosh. “We're always trying to achieve the best results, but a cystectomy is a life-altering procedure, so for the bladders that can stay in place, let’s keep them there.”
Non-invasive bladder cancer can often be successfully addressed with a surgical procedure and treatment administered directly into the bladder, which is an area of expertise for Dr. Abbosh. But once cancer makes its way into the muscle of the bladder, it requires multidisciplinary collaboration among medical oncology, urology, and possibly radiation oncology and others. This is how the arc of research by Drs. Abbosh and Plimack becomes tightly linked.
“I've been the beneficiary of being in a place that has a lot of clinical researchers like Dr. Plimack and other surgeons and oncologists – not only do we have numerous ongoing clinical trials, but they’re also very willing to collaborate with people like me and with our lab,” Dr. Abbosh says. “So when Dr. Plimack and others design trials, they can grab me by the elbow and say, ‘Hey, how do we integrate you into this?’ I’ve been lucky to be at the right place and time to be a part of it.”
The Abbosh lab delivers key translational research for direct patient benefit, with a primary aim of achieving and identifying the pT0 state (no evidence of remaining disease) in patients with localized bladder cancers. These projects include novel diagnostic tests to detect residual bladder cancer after presurgical chemotherapy; novel mouse models on which to develop the basis for personalized medicine trials; and annotation and experimental manipulation of immune response to chemotherapy for patients with bladder cancer, among others.
Through a grant from the National Institutes of Health, Dr. Abbosh is also in the middle of a five-year study of a urine test to detect residual bladder cancer in patients who have undergone treatment before bladder removal. He and his team analyze urine from patients treated in five different clinical trials, including the RETAIN BLADDER trials. After isolating DNA from the urine, they look for mutations that are derived from the tumor to indicate its presence – or the lack of it.
Meanwhile, Dr. Plimack is internationally renowned for her expertise and development of new therapies for bladder and kidney cancers. Recognized in 2022 as a Highly Cited Researcher by Clarivate, which honors a select few worldwide who have demonstrated exceptional influence in their fields, she focuses her research on biomarkers predictive of response to neoadjuvant chemotherapy in bladder cancer; refining neoadjuvant chemotherapy regimens for bladder cancer; early-stage clinical trials of novel agents; and immunotherapy in genitourinary malignancies.
Dr. Plimack’s work has formed the basis of a biomarker-directed bladder preservation platform led by Fox Chase investigators, and she has led and published the results of a multicenter clinical trial in metastatic bladder cancer funded by Stand Up To Cancer. She has also been highly active in drug development on steering committees and data safety boards of trials that have led to the approval of multiple new agents used to treat patients with genitourinary cancers.
“Our multidisciplinary team here at Fox Chase is tightly integrated and aligned around research on the best approaches for clinical care,” Dr. Plimack says. “With the approval of multiple new drugs for bladder cancer in recent years, it's an exciting time to be able to provide really good care for these patients through approaches, philosophies, concepts, drugs and technology that we may not have had or known about before.”
Another key element of their shared approach to bladder cancer care is providing exactly what each individual needs. With a common goal to avoid excessive treatments, Drs. Abbosh and Plimack emphasize the optimization of treatment on a personalized, patient-to-patient basis, based primarily on biology, biomarkers, and clinical assessments.
“We've come a long way in that bladder cancer is very curable, and when you get to that point, then the strategy moves away from ‘How do we do more,’ and instead it’s how we can do less, tailor the therapy to the patient, and still achieve the same cancer control outcome without putting people through the wringer,” Dr. Abbosh says.
Dr. Plimack concurs: “We're really focused on right-sizing the treatment for the patient. We want to intervene only where it's impactful, not missing any opportunities and at the same time not overdoing it. That's an overarching goal at Fox Chase and one of the reasons I love practicing here.”
Along those lines, both doctors say Fox Chase sets itself apart through its true collaboration on new solutions for cancer in a close-knit, patient-centric setting. The cross-disciplinary emphasis and clinical trial expertise that brings researchers and physicians onto the same team have a significant compounding effect, driving better patient care and real bench-to-bedside results.
“We have so many really smart people at Fox Chase, but we are not ego-driven here,” Dr. Plimack says. “Anyone could very easily be thinking about how to put themselves up at the podium, but the goal across the board is the same: to take good care of people and to make new discoveries. One person doesn’t own what we do – we all feed off that environment of sharing opportunities and responsibilities, and it really brings us together.”
Fox Chase is home to some of the nation’s top genitourinary cancer specialists, with a robust research program and cutting-edge clinical trials that are not easily accessible elsewhere. As research is accelerating to detect and effectively treat bladder cancer, new techniques are becoming available that are likely not only to prolong life, but also to maintain quality of life.
That is the ultimate goal of the exhaustive studies by clinicians and researchers like Drs. Abbosh and Plimack – and a key benefit of Fox Chase’s elite standing as an NCI-designated Comprehensive Cancer Center, currently one of only 51 in the nation. These extraordinarily talented scientists thrive in an environment that is ideal for making fundamentally important discoveries.
With its long history of breakthrough research, Fox Chase continues to lead the field with seminal scientific discoveries that have key translational implications. The insights gleaned from these laboratory studies can be directly applied to patient care while safely evaluating new approaches to preventing and treating cancer through clinical trials, which may eventually drive standard protocols with far-reaching implications.
Through support from its partnership with Temple Health’s oncology research, treatment and prevention programs, Fox Chase Cancer Center makes a world of difference in Northeast Philadelphia and all other communities it serves.
As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for more than 100 years. With a singular focus on cancer, we combine discovery science with state-of-the-art clinical care and population health.
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