Prognostic Value of the De Ritis Ratio for Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing [(177)Lu]Lu-PSMA-617 Radioligand Therapy

SIMPLE SUMMARY: Radioligand therapy with [(177)Lu]Lu-PSMA-617 is an effective treatment for patients with prostate cancer. However, survival after radioligand therapy differs widely because patients respond differently to treatment but also enter therapy with an individual set of risk factors. We retrospectively analyzed the prognostic factors and survival data of 91 patients who were treated in our hospital. We found that patients with more previous lines of chemotherapy, higher levels of the prostate-specific antigen, and a higher “De Ritis ratio” (calculated from two laboratory parameters) lived—on average—for a shorter time after radioligand therapy than patients without these factors. We developed a score to better define patients with different survival outcomes after treatment. Between the highest and lowest risk groups, survival ranged from approximately 5 months to 28 months, respectively. If an independent validation of this score is successful, it could help doctors identify those patients not likely to benefit from radioligand therapy. ABSTRACT: The De Ritis ratio (=aspartate transaminase/alanine transaminase) has shown prognostic value in different cancer types. This is the first such analysis in prostate cancer patients undergoing radioligand therapy (RLT) with [(177)Lu]Lu-PSMA-617. This retrospective monocentric analysis included 91 patients with a median of 3 RLT cycles (range 1–6) and median cumulative activity of 17.3 GBq. Univariable Cox regression regarding overall survival (OS) included age, different types of previous treatment, metastatic patterns and different laboratory parameters before RLT. Based on multivariable Cox regression, a prognostic score was derived. Seventy-two patients (79%) died (median follow-up in survivors: 19.8 months). A higher number of previous chemotherapy lines, the presence of liver metastases, brain metastases, a higher tumor load on PSMA-PET, a higher prostate-specific antigen (PSA) level, lower red blood cell count, lower hemoglobin, higher neutrophil-lymphocyte ratio and higher De Ritis ratio were associated with shorter OS (each p < 0.05). In multivariable Cox, a higher number of chemotherapy lines (range, 0–2; p = 0.036), brain metastases (p < 0.001), higher PSA (p = 0.004) and higher De Ritis ratio before RLT (hazard ratio, 1.27 per unit increase; p = 0.023) remained significant. This prognostic score separated five groups with a significantly different median OS ranging from 4.9 to 28.1 months (log-rank test, p < 0.001). If validated independently, the De Ritis ratio could enhance multifactorial models for OS after RLT.