[<sup>177</sup>Lu]Lu-PSMA radioligand therapy in younger prostate cancer patients: A matched-pair analysis between patients ≤ 65 and ≥ 70 years old.
[177Lu]Lu-PSMA RLT shows comparable efficacy in younger prostate cancer patients compared to older patients, with a slightly better safety profile.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study evaluated the efficacy and safety of Lutetium-177 ([177Lu]Lu)-Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) in prostate cancer patients aged ≤65 years compared to those aged ≥70 years. A total of 102 patients were matched based on Gleason score, baseline PSA, and prior chemotherapy status. The findings indicated similar efficacy in both age groups with some differences in safety profiles.
Abstract
PURPOSE: In prostate cancer, Lutetium-177 ([177Lu]Lu )-Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) shows benefit even in earlier stages of the treatment course, potentially leading to broader application also in younger patients. However, evidence regarding its efficacy and safety in this population remains limited. METHODS: Based on Gleason score, baseline prostate specific antigen (PSA) and prior chemotherapy status, 51 patients ≤ 65 years of age were matched to 51 patients ≥ 70 years. All patients were scheduled for [177Lu]Lu-PSMA RLT. Efficacy was evaluated using relative PSA changes after two cycles, along with progression-free survival (PFS, defined as time from 1st RLT to ≥ 25% PSA increase from nadir) and overall survival (OS). Safety was assessed by changes in estimated glomerular filtration rate (eGFR), hemoglobin (Hb), white blood cells (WBC) and platelets from baseline to nadir, alongside Common Terminology Criteria of Adverse Events (CTCAE 5.0) grading for chronic kidney disease (CKD), anemia, leukocytopenia and thrombocytopenia. RESULTS: RLT showed similar efficacy in both age groups with comparable PSA changes after two cycles (younger patients: -8%; Interquartile range [IQR], -55 to 46% versus older subjects: -20%, IQR, -71 to 46%; P = 0.766). No significant differences were observed for PFS (P = 0.882) and OS (P = 0.17). RLT was safe in both age groups, although eGFR, Hb, WBC and platelets declined significantly in both cohorts (P ≤ 0.001 each). Younger patients showed slightly better tolerance, with smaller decreases in Hb (P = 0.021) and platelets (P = 0.013), along with fewer grade 3 events (young vs. old: anemia, 2 vs. 7 and thrombocytopenia, 0 vs. 2). CONCLUSION: [177Lu]Lu-PSMA RLT is a safe and effective treatment option in patients ≤ 65 years old, demonstrating comparable efficacy and a slightly more favorable safety profile relative to older patients. These findings support the use of [177Lu]Lu-PSMA RLT regardless of age, which may be of importance given recent expansion of the indication spectrum.
Background
This paper addresses the efficacy and safety of [177Lu]Lu-PSMA RLT in younger prostate cancer patients, a demographic where evidence is limited. Previous studies have primarily focused on older populations, leaving a gap in understanding the treatment's applicability in younger patients. The findings could influence treatment decisions and expand the indications for RLT in younger cohorts.
Methods
The study utilized a matched-pair analysis design, comparing 51 patients aged ≤65 years to 51 patients aged ≥70 years based on Gleason score, baseline PSA, and prior chemotherapy. All patients were scheduled for [177Lu]Lu-PSMA RLT, with efficacy assessed through relative PSA changes after two cycles, progression-free survival (PFS), and overall survival (OS). Safety was evaluated by changes in eGFR, Hb, WBC, and platelets, along with CTCAE grading for adverse events.
Results
The primary endpoint showed a PSA change of -8% in younger patients and -20% in older patients after two cycles, with a P-value of 0.766 indicating no significant difference. Additionally, PFS and OS did not differ significantly between the two age groups (P=0.882 and P=0.17, respectively). Both age groups experienced significant declines in eGFR, Hb, WBC, and platelets (P≤0.001 each). Younger patients exhibited better tolerance with smaller decreases in Hb (P=0.021) and platelets (P=0.013).
Interpretation
The results suggest that [177Lu]Lu-PSMA RLT is similarly effective in younger patients compared to older ones, although the clinical significance of the observed PSA changes may require further investigation. The study's limitations, including the small sample size and potential confounding factors, may affect the generalizability of the findings. These results imply that age alone may not be a determining factor in the efficacy of RLT, but further research is needed to confirm these observations.
Key findings
- -8% PSA change in younger patients after two cycles, IQR -55 to 46%, P=0.766.
- -20% PSA change in older patients after two cycles, IQR -71 to 46%, P=0.766.
- No significant difference in progression-free survival (PFS), P=0.882.
- No significant difference in overall survival (OS), P=0.17.
- Significant decline in eGFR, Hb, WBC, and platelets in both cohorts, P≤0.001 each.
- Younger patients had fewer grade 3 events: anemia (2 vs. 7) and thrombocytopenia (0 vs. 2).
Limitations
- observational study design
- small sample size (n=102)
- potential confounding factors due to matching criteria
- no long-term follow-up reported