Multi-Tracer PET Imaging Links Cancer Cell Diversity to Reduced Survival

Summary: A new study highlights the prevalence of intrapatient intermetastatic heterogeneity in 83% of metastatic castration-resistant prostate cancer patients, linking diverse cancer cell subtypes identified through multi-tracer PET imaging to reduced survival and informing personalized treatment strategies.

Key Takeaways

• High Prevalence of IIH: Intrapatient intermetastatic heterogeneity (IIH) was identified in 83% of metastatic castration-resistant prostate cancer patients using whole-body multi-tracer PET imaging.
• Impact on Survival: Patients with IIH showed significantly reduced overall survival, with distinct tracer positivity patterns linked to higher mortality rates.
• Advancing Precision Medicine: Early detection of IIH using multi-tracer PET imaging offers valuable insights for tailoring personalized treatment plans and enhancing therapeutic decision-making.

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A new whole-body multi-tracer PET imaging method can accurately identify evolving cancer cell subtypes within different metastases in the same prostate cancer patient, according to research published in The Journal of Nuclear Medicine. This phenomenon, known as intrapatient intermetastatic heterogeneity (IIH), was observed in 83% of patients with metastatic castration-resistant prostate cancer (mCRPC). Identifying these diverse cancer cells provides critical insights to help physicians develop personalized treatment plans.

Evolving Cancer Cells Complicate Treatment Decisions

Advances in medicine now allow mCRPC patients to undergo several types of treatment targeting different cancer pathways. Multiple treatments, however, cause cancer cells to change, resulting in IIH. These changes to challenges in monitoring cancer treatment resistance, defining progression, and making therapeutic decisions.

“Prior to this study, evidence of IIH in prostate cancer was determined by biopsy from only a few metastatic sites, either late in the disease course or after rapid autopsy,” says Frédéric Pouliot, MD, PhD, FRCSC, clinician-scientist and associate professor in the department of surgery, urology division, at CHU de Québec–Université Laval Research Center in Quebec City, Quebec, Canada. “By using whole-body PET/CT to scan for IIH earlier, clinicians can integrate IIH knowledge in their treatment decisions, including radiopharmaceutical therapy.”

Cancer Diversity in Advanced Prostate Cancer

In the study, authors assessed the prevalence of IIH in mCRPC and its associated impact on overall survival. Whole-body PET imaging was conducted with three distinct PET tracers (¹⁸F-FDG, ⁶⁸Ga-PSMA-617, and ⁶⁸Ga-DOTATATE). Ninety-eight patients were included in the primary analysis, which included ¹⁸F-FDG and ⁶⁸Ga-PSMA-617 PET/CT scans. Thirty-seven patients who were found to have at least one ¹⁸F-FDG-positive/⁶⁸Ga-PSMA-617-negative lesion received an additional ⁶⁸Ga-DOTATATE PET/CT scan.

IIH prevalence in the 98 patients receiving ¹⁸F-FDG and ⁶⁸Ga-PSMA-617 PET/CT scans was 82.7%. In the patients who underwent ⁶⁸Ga-DOTATATE PET/CT, the prevalence of IIH was 83.8% and 16.2% had positive lesions. Based on the individual metastasis uptakes of the three tracers in each patient, at least 12 different mCRPC IIH combinations were found.

IIH Patterns Correlate with Survival

The overall survival of all enrolled patients was 10.2 months. Patients with IIH had a median overall survival of only 9.5 months and a 2.7-fold higher probability of dying of prostate cancer during the study follow-up than those without IIH. Those with at least one ¹⁸F-FDG-positive/⁶⁸Ga-PSMA-617-negative lesion had a median overall survival of only 5.6 months and a 2.8-fold higher probability of dying of prostate cancer during the study follow-up than those with only ⁶⁸Ga-PSMA-617-positive lesions. Finally, patients who had at least one ⁶⁸Ga-DOTATATE-postive lesion had a poor median overall survival of 3 months and a 5-fold higher probability of dying of prostate cancer during the study follow-up than those without.

 “These findings show an unexpected high prevalence of IIH in mCRPC patients and demonstrate that IIH and some patterns of tracer positivity are associated with decreased survival,” says Pouliot. “In the future, molecular imaging with multiple tracers may have a novel and important role for precision medicine in mCRPC and other cancers.”