Cancer researchers and clinicians are driven by a shared goal – to improve patient quality of life and survival by developing and implementing the most effective treatments and diagnostic tools. Given the substantial risks associated with many cancer treatments, therapeutic regimens must be individually tailored to effectively eradicate cancer while minimizing harmful side effects. Precision diagnostics that detect cancer with high sensitivity and specificity provide clinicians with more nuanced insights to help make better-informed treatment decisions.
A study recently published in Cancer examines one of the latest innovations in precision diagnostics for prostate cancer. Prostate cancer affects over a million men each year and is the second leading cause of cancer-related death in men. The disease has an excellent prognosis when caught early, but its behavior and response to treatment become far more variable in advanced or recurrent disease. Accurately staging prostate cancer to determine its extent and severity is crucial for making appropriate treatment choices.
Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is an imaging technique that detects prostate cancer metastases with higher sensitivity and specificity than conventional imaging methods. A small molecule radiotracer is used to detect PSMA, a protein that is expressed on the surface of prostate cancer cells, and a positive fiding can be a sign of cancer progression. Although the technique was approved for clinical use just five years ago, it’s already reshaping prostate cancer diagnosis and treatment management.
PSMA-PET significantly improves staging accuracy at biochemical recurrence, characterized by rising blood levels of prostate cancer markers after treatment. Biochemical recurrence serves as an early indicator for potential disease persistence or return, but it doesn’t always mean the patient will proceed to develop metastatic cancer. Clinicians now increasingly take PSMA-PET findings into consideration when making treatment decisions for these patients. The underlying assumption here is that more accurate staging leads to better treatments, ultimately improving survival in a meaningful way.
It's a logical assumption, but does it hold true? Might we be overestimating the value of PSMA-PET for tailoring salvage treatment? How do the outcomes of a tailored approach compare to standard approaches that only consider clinical risk?
To address such questions, the Etzioni group in the Public Health Sciences Division develops mathematical models to explore the outcomes of various counterfactual clinical scenarios and decisions. Dr. Ruth Etzioni explains,
We want to confirm whether the beliefs and assumptions that underlie changes in practice, that typically happen in response to precision diagnostics but in the absence of randomized studies and data, are as favorable as people expect.
Clinical studies examining survival outcomes from PSMA-PET-informed therapy are underway, but more research is needed before its long-term prognostic value can be validated. Yet as the authors note, "despite this evidence gap, PSMA-PET is already being used to guide treatment decisions at biochemical recurrence”.
So, how should decision-making be handled in the meantime?
Research associate Dr. Kemal Gogebakan developed a decision analytic model to explore how long-term survival is impacted when PSMA-PET is used to guide treatment management in biochemical recurrence. Decision analytic models are mathematical frameworks designed to evaluate complex decision problems and reveal relationships between assumptions and outcomes. In the absence of robust evidence, these models help manage uncertainty and guide decisions in a structured, objective manner, rather than relying primarily on the experiences and assumptions of an individual clinician.
By weaving together data from published studies, prospective clinical trials, and physician questionnaires, the model compares two therapeutic approaches and projects potential lifespan gain when PSMA-PET is used to guide therapy. It also incorporated a set of parameters that could be adjusted depending on patient prognosis and treatment intensity to generate a range of expected survival benefit.
The model predicts a modest increase in average patient lifespan ranging between ~4.5-10 months when PSMA-PET guides treatment, compared to using a standard treatment approach based solely on established clinical guidelines. It is important to note that this model reflects a snapshot of our current understanding of prostate cancer and that it only considers one tailored treatment approach. In reality, a mixture of tailored treatments are likely offered in practice.
The landscape for prostate cancer care will inevitably evolve as we gather more data and make new discoveries. The broader value of this work extends beyond PSMA-PET and prostate cancer. With an ever-accelerating pace of medical advances, mathematical modelling offers a practical way to evaluate the implications of new diagnostics and make the uncertainties that shape early clinical decisions more explicit.
The spotlighted research was funded by the National Cancer Institute.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium members Dr. Amir Iravani (UW) and Dr. Ruth Etzioni (Fred Hutch) contributed to this research.
Gogebakan KC, Elsisi Z, Montano‐Campos F, Owens L, Zhao Y, Gulati R, Ferdinandus J, Fendler WP, Calais J, Hope TA, Carlsson S, Fainberg J, Laudone V, Kunst N, Berlin A, Schipper M, Barbour A, Iravani A, & Etzioni R. 2025. Prostate‐specific membrane antigen positron emission tomography/computed tomography imaging as a precision diagnostic at prostate cancer recurrence after radical prostatectomy: Modeling long‐term survival. Cancer. DOI: 10.1002/cncr.70131