(UroToday.com) The 2022 EAU annual meeting featured a game changing session, including a discussant presentation by Dr. Tobias Maurer discussing the clinical context of the initial results of LuTectomy, a single-arm study of the dosimetry, safety, and potential benefit of 177Lu-PSMA-617 prior to radical prostatectomy. Dr. Maurer started by highlighting that 177Lu-PSMA-617 has been on the rise since ~2015, the year the SNMMI’s Image of the Year was awarded to the group in Heidelberg, Germany:
Since then, TheraP1 and VISION 2 have established the role of 177Lu-PSMA-617 in mCRPC. So, Dr. Maurer asks “Is LuTectomy the role for 177Lu-PSMA-617 in the future?”
Dr. Maurer highlighted that the primary endpoint of LuTectomy was median absorbed radiation dose, which was a median of 48 Gy in the prostate and 50 Gy in the lymph nodes. LuTectomy also had meaningful secondary endpoints, including median PSA reduction (~43%), pathological response (8/10 showed a treatment effect), 177Lu-PSMA-617 safety (no grade 2-5 adverse events), and surgical safety (no Clavien-Dindo 3-5 events). But, Dr. Maurer notes that there were no pathological complete responses or cases of minimal residual disease, which perhaps will occur with the patients receiving 2 cycles of 177Lu-PSMA-617. Furthermore, LuTectomy is only a feasibility trial, thus no answers can be expected for oncological outcomes in a small single-arm study. Therefore, it is important that we should not offer PSMA radioligand therapy in earlier lines of prostate cancer treatment outside of clinical trials. Dr. Maurer also noted that in the publication of the clinical trial protocol,3 the authors stated that “dosimetry estimates indicate that 177Lu-PSMA-617 has the potential to replace or augment surgery or external-beam radiotherapy in the first-line setting”, which in his opinion, based on these initial results, is unlikely to be the case.
Is neoadjuvant 177Lu-PSMA-617 feasible in Germany where Dr. Maurer works? If an estimated 70,000 patients are eligible, and assuming 10,000 patients have appropriate general health, elevated risk features, and PSMA avid lesions with an SUVmax > 20, after factoring in availability (PET/CT, radiochemicals, personnel, treatment capacity, at approximately 50 sites), and cost (PSMA PET/CT 2,000 Euros x 2 scans + 177Lu-PSMA-617 6,000 Euros/cycle) there is the potential for a significant impact on the healthcare system for neoadjuvant 177Lu-PSMA-617.
Dr. Maurer concluded his discussion of the LuTectomy trial by emphasizing that this trial offers great translational research options, specifically with regards to dosimetry and response to therapy (imaging, pathology, immune gene profiling, etc):
Presented by: Tobias Maurer, MD, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.
- Hofman MS, Emmett L, Sandhu S, et al. [(177)Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): A randomized, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804.
- Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
- Dhiantravan N, Violet J, Eapen R, et al. Clinical Trial Protocol for LuTectomy: A Single-arm Study of the Dosimetry, Safety, and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy. Eur Urol Focus. 2021 Mar;7(2):234-237.