2 research outputs found
Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy
At present, little is known about the molecular imaging-based response assessment of
prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177LuPSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated
the response to RLT using both molecular imaging and biochemical response assessments, and their
potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles
of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained
about 2 weeks prior to the first and 4â6 weeks after the second cycle. Molecular imaging-based
response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria.
âTLR and âSUV were significantly correlated with âPSA (p < 0.001, each). After a median follow-up
of 49 months, the median PFS (95% CI) was 8.0 (5.9â10.1) months. In univariate analysis, responders
showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median:
10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0
and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable
analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was
good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could
be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free
survival (PFS) of this treatment modalit
177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study)
Purpose Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety
and efcacy of radioligand therapy (RLT) targeting prostate-specifc membrane antigen (PSMA) in men with metastatic
castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples
treated in everyday practice.
Methods We analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecu tive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment
following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated
(median age 70 years; prior taxanes 74.0%, 188/254), with lateâend-stage disease (visceral metastasis in 32.7%, 83/254).
Primary endpoints were response to RLT, defned by changes from baseline serum prostate-specifc antigen (PSA) concen tration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with KaplanâMeier statistics, and
caregiver-reported and patient-reported safety. Unless noted, median (minimumâmaximum) values are given.
Results Patients received 3 (1â13) 177Lu-PSMA-617 activities (6.5 [2.5â11.6] GBq/cycle) every 5.7 (3.0â11.0) weeks. Best
response wasâ„50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confdence interval [95%CI]
4.4â6.6) months and OS, 14.5 (95%CI 11.5â17.5) months. In multivariable Cox proportional-hazards modeling, response
to the initialâ€2 RLT administrations was the strongest signifcant prognosticator related to OS (hazard ratio 3.7 [95%CI
2.5â5.5], p<0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade
3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%).
RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%).
Conclusions In a large, prospectively observed âreal-worldâ cohort with late-stage/end-stage mCRPC and conventional
treatment failure, 177Lu-PSMA-617 RLT was efective, safe, and well-tolerated. Early biochemical disease control by such
therapy was associated with better OS. Prospective study earlier in the disease course may be warranted