Metastatik Prostat Kanseri Olgularında Tedavi Amacıyla Kullanılan 177 Lu-PSMA Tedavisinin Başarısının Klinik, Görüntüleme ve Biyokimyasal Parametreler İle İlişkisinin Belirlenmesi-Gözlemsel İlaç Çalışması

Abstract

Because of the distinct heterogeneous patient group and rapid disease course, it is critical to identify the patients who will benefit from 177Lu-PSMA treatment and who will progress rapidly despite treatment before the therapy. The aims of the study are to evaluate the success of 177 Lu-PSMA treatments by using progression-free and overall survival, clinical, PSA, PET response criteria and to determine the clinical, imaging and biochemical parameters predicting PSA response. In our study, patients who received 2-6 cycles of 177Lu-PSMA treatment for a period of 3 years were evaluated prospectively. The serum PSA value was monitored regularly every two weeks during the treatment process and after 3 month of the end of the therapy. Biochemical response was evaluated as recommended in Prostate Cancer Clinical Trial Working Group3 (PCWG3). As for the PET response, the patients were evaluated with 68Ga-PSMA PET/CT 6-8 weeks after the second therapy and 8-12 weeks after completion of the therapy to four. PET responses were categorized according to modified EORTC Response Criteria. For clinical response, patients' ECOG and Karnofsky performance scores, pain intensity with visual analog scale (VAS), changes in quality of life with EORTC QLQ-C30 questionnaires were followed. EORTC OH-15 questionnaire, complete blood count, blood biochemical tests were followed up every two weeks during the treatment process and 3 months after the end of the treatment for possible side effects. The relationship between clinical, laboratory, molecular imaging parameters and PSA response was investigated before and during treatment with 177Lu-PSMA. During the median follow-up of 10.93 months, 24 (46.2%) of the patients died, the median overall survival was 17 months, and the median progression-free survival was 6.73 months. Any decrease in PSA in 44 (84.6%) patients at follow-up during treatment, ≥50% reduction in PSA at any time in 31 patients (59.7%), ≥50% reduction in PSA after 3 months of the therapy in 25 patients (49%) were seen. In 14 of our patients (26.9%), 26,9% of the patients that initially showed any response, showed PSA progression during the therapy or after 3 months of the therapy completion. According to the PSA response curve patterns, 26 patients (50%) had "treatment response", one patient (1.9%) had stable disease, 10 patients (19.2%) had "acquired resistance", 15 patients (28.8%) had " treatment resistance”. In interim 68Ga-PSMA PET, 16 patients (34.8%) had progressive disease, 3 (6.5%) stable disease, 3 (6.5%) mixed response, 23 (50%) ) partial response, complete response in 1 (2.2%), while in PET end of the therapy progressive disease in 9 patients (45%), stable disease in 1 patient (5%), partial response in 10 patients (50%) were detected. With 177Lu-PSMA treatment, statistically significant pain palliation was provided in our patients. 28% of the patients no longer needed any kind of analgesics (25% of the patients no longer needed strong opioids). According to the EORTC-QLQ C30 questionnaires, 177Lu-PSMA led to statistically significant decrease in loss of appetite and pain symptomes, compared to the pre-treatment treatment. In univariate analysis to predict the best PSA response to be ≥50%, the use of 2nd generation ADT, TLG / TL-PSMA, SUVmax in the dominant lesion in 68Ga-PSMA PET / CT, FDG and PSMA PET / CT mismatch, bone scintigraphy- PSMA PET / CT compliance, PSA, LDH and ALP response after one cycle of 177Lu-PSMA therapy were found to be associated, while in multivariate analysis, PSA response after 1 cycle of 177Lu-PSMA treatment remained statistically significant. In univariate analysis to predict the PSA response after 3 months of completion of the therapy to be ≥50%, the use of 2nd generation ADT, bone scintigraphy- PSMA PET / CT compliance, TLG / TL-PSMA, MTV/TTV, FDG and PSMA PET / CT mismatch, PSA, LDH response after one cycle of 177Lu-PSMA therapy were found to be associated, while in multivariate analysis, PSA response after 1 cycle of 177Lu-PSMA treatment remained statistically significant. Anemia in 22 patients (42.3%), leukopenia in 18 patients (34.6%), neutropenia in 6 patients (11.4%), lymphopenia in 37 patients (71.2%), thrombocytopenia in 13 patients (25%), increase in creatinine in 4 patients (5.8%), and dry mouth in 18 patients (34.6%) developed. Although the majority of the adverse effects that developed were low-grade, grade 3 anemia, grade 3-4 lymphopenia and grade 3-4 thrombocytopenia rates were 11.5%, 25%, and 8% respectively. In conclusion, 177Lu-PSMA treatment is an effective treatment, especially in terms of pain palliation, with its rare severe side effect profile. In-vivo determination of heterogeneity by molecular imaging is of clinical importance. PSA response after a cycle of 177Lu-PSMA therapy successfully predicts both the best response and the PSA response at 3 months post-treatment.