PT - JOURNAL ARTICLE AU - Taeger, Philipp AU - Hammes, Jochen AU - Hohberg, Melanie AU - Wild, Markus AU - Schomaecker, Klaus AU - Kobe, Carsten AU - Pfister, David AU - Heidenreich, Axel AU - Dietlein, Markus AU - Schmidt, Matthias AU - Drzezga, Alexander TI - Discrete evaluation of multi-cycle Lu-177-PSMA-617-therapy effects on bone versus lymph node metastases in patients with metastasized castration‑resistant prostate cancer (mCRPC) DP - 2018 May 01 TA - Journal of Nuclear Medicine PG - 523--523 VI - 59 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/59/supplement_1/523.short 4100 - http://jnm.snmjournals.org/content/59/supplement_1/523.full SO - J Nucl Med2018 May 01; 59 AB - 523Objectives: The objective of this study was to separately evaluate the specific effects of Lu-177-PSMA-617-therapy on lymphatic (LM) and osseous metastases (OM) in patients with mCRPC. Methods: 20 patients with mCRPC (average values for age: 71.1 years, Gleason-Score: 8.4, disease duration: 6.7 years) underwent up to 3 cycles of PSMA therapy (avg: 2.7) in our clinic and received Ga-68-PSMA-PET/CT scans (PET-Scan) before, during and after therapy.a) The response of LM was evaluated according to the guidelines of the prostate cancer working group and RECIST 1.1. Short axis diameters of LM were compared over the course of therapy. PSMA-positive lesions with a diameter of > 1.0 centimeters were used as target-lesions. In addition the SUVmax of all PSMA-positive LM was determined. b) To evaluate the OM load, we used the automated quantification tool ‘EBONI’ which was recently introduced by our group. It automatically determines total PSMA-positive OM volume, SUVmean, SUVmax and number of OM. Patients were divided into 3 groups according to the PSA-response in analogy to RECIST 1.1: PSA-Responder (PSAR): decrease of >30%, PSA‑Nonresponder (PSAN): increase of >20% and stable (PSAS) with PSA levels in between. Results: An average dose of 6.3 GBq was administered per cycle. Following therapy, 9 patients were PSAR, 4 PSAS and 7 PSAN. All patients showed OM, 12 showed LM suitable for RECIST evaluation (4 PSAR, 3 PSAS, 5 PSAN), 5 patients showed exclusively non target LM (<1cm) throughout the course of therapy and were therefore classified as stable (4 PSAR, 1 PSAS). 1.) Although SUVmax declined (avg. -9.2 or -22%, p<0.01) in most OM, total PSMA-positive OM volume increased in most cases, even after 3 cycles (avg. +380 ml or + 150%, p<0.01).2.) SUVmax decreased in LM on avgerage by -55.4 or -48% (p<0.01). Diameters of LM decreased on avg. by 20.2 mm or 23% (p<0.05). However, according to RECIST-criteria, this decrease qualified for therapy response in only 18% of patients (3/17, 3 PSAR) and for stable disease in additional 29% of patients, despite the latter showing significant SUV-response. In 5 patients new LM emerged during therapy.3.) Neither OM nor LM response correlated clearly with PSA-response. PSA-response did not allow to differentiate between therapy responders and non-responders in terms of PSMA-uptake, tumor diameter or volume.Conclusion: Lu-PSMA-therapy shows therapeutic effect on the viability of OM (in terms of max. PSMA-expression) in most cases, however without completely preventing expansion of metastatic disease. Regarding LM, PSMA-therapy appears to result in more distinct regression in size and SUVmax. However 25% of patients showed new LM despite response of existing lesions. RECIST-criteria for response and stable disease were met in 47% of cases with LM. Of note, RECIST-criteria would have missed PSMA-positive lymph nodes at baseline in 25% of cases, potentially limiting its value for therapy control. Furthermore, therapy effects on SUV, affected bone volume and lymph node diameters were mostly independent of PSA response, also questioning the value of PSA-monitoring as a suitable response parameter. Generally these findings imply a complex therapeutic response to Lu-PSMA therapy which depends on the pattern of metastatic disease and requires a differentiated monitoring strategy, ideally involving PSMA-PET.