Abstract
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Purpose: Treatment regimens with predefined treatment cycles of Lu-177-PSMA-617 radioligand therapy (RLT) may be suboptimal in patients with more aggressive high tumor load metastatic castration-resistant prostate cancer (mCRPC). We assessed the outcome, toxicity and clinical response in patients receiving extended RLT with a mean cumulative activity of >45 GBq and no other promising treatment alternatives.
Methods: Eighteen patients with high tumor burden (miTNM classification, PROMISE) and low PSA-doubling time of <2 months were treated with 6.7±1.2 GBq Lu-177-PSMA-617 at 9±8 weeks interval. Treatment was discontinued in case of 1) biochemical progression defined as a rise of >30% in PSA-Level from baseline (PCWG3), 2) progressive disease in routine Ga68-PSMA-11 PET/CT examinations done every 2-3 cycles using mPERSIST criteria, 3) new lesions in intra-therapeutic Lu-177-PSMA-617 scintigrams, 4) the onset of significant renal or hematological toxicity (grade 3/4) using maximal Common Terminology Criteria for Adverse Events (CTCAE v. 5.0), 5) xerostomia (grade 3/4, CTCAE v.5), 6) pain exacerbation, defined as >2 step increase in VAS, or 7) clinical deterioration (ECOG >2). Progression free survival analysis was performed with the Kaplan-Meier curve method.
Results: Patients were treated with 10±2 cycles. Mean cumulative activity was 67.1±14.6 GBq, resulting in a median cumulative renal dose of 31.5±11.3 Gy. Mean eGFR declined from 90.4 ml/min/1.73 m2 at baseline to 72.4 ml/min/1.73 m2 after a mean follow-up period of 17±9 months (p=0.003). Moderate renal function reduction (grade 2) was observed in 4 patients (22 %) but no patient developed severe nephrotoxicity (grade 3/4). Significant pancytopenia of grade 3 occurred in 1 patient (6%) leading to therapy cessation after 7 cycles. Eight patients (44%) developed xerostomia (grade 1-2) after 5±2 cycles. The median progression free survival (PFS) was 31 months (CI 95 % 14-48). Five out of 7 patients with painful metastases (VAS >5) improved significantly (VAS-reduction >2 steps) throughout the treatment and no patient showed pain progression. Two of three patients starting the treatment with restricted performance status (ECOG 2) at baseline improved to grade 1.
Conclusions: Long progression free survival times and the absence of serious adverse events in this patient group encourage further evaluation of extended radioligand therapy in patients with advanced disease. Figure: 68Ga-PSMA PET/CT images of a patient undergoing extended therapy with 10 cycles during 30 months until progression.
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