Background: 177LuPSMA is an effective treatment in metastatic castrate-resistant prostate cancer (mCRPC). Our ability to assess response rates and adjust treatment may be improved using predictive tools. This study aimed to evaluate change in 177Lu-PSMA-SPECT quantitative parameters to monitor treatment response. Methods: 127 men with progressive mCRPC previously treated with androgen signaling inhibition (99%) and chemotherapy (71%) received a median 3 (IQR 2-5) doses Lu PSMA I&T 8 GBq (IQR 8-8.5). Imaging included 68Ga-PSMA-11 PET-CT (SUVmax >15 at a single site and >10 at all sites > 2cm), diagnostic CT, and 177Lu-SPECT/CT (Lu-SPECT) vertex to mid-thigh (24 hours following treatment). Lu-SPECT quantitative analysis was undertaken at cycle-1 (baseline) and 2 (week 6) of treatment. Clinical and biochemical results were assessed to evaluate PSA progression free (PSA-PFS) and overall survival (OS). Results: 58% (74/127) had PSA reduction > 50%. The median PSA-PFS was 6.1 months [95%CI 5.5-6.7] and OS 16.8 months [95% CI 13.5-20.1]. At time of analysis 41% (52/127) were deceased. 76% (96/127) had analyzable serial 177Lu-SPECT/CT imaging at baseline and week-6. SPECT-total tumor volume (SPECT-TTV) was reduced between baseline and week-6 in 74% (71/96, median -193 (IQR -486 to -41). Any increase in SPECT-TTV between baseline and week-6 was associated with significantly shorter PSA-PFS (HR 2.5 (95%CI 1.5-4.2) p 0.0008) but not OS. Median PSA-PFS in those with an increase in SPECT-TTV was 3.7 months (95%CI 2.8-6.8), compared to 6.7 months (95%CI 5.8-10.6) with no increase in SPECT-TTV. An increase in SPECT-TTV greater than 20% was also associated with PSA-PFS (HR 1.9 (95%CI 1.2-3.0) p 0.008), but less significantly than any change in SPECT-TTV. There was a significant difference in PSA-PFS between patients with both increased PSA and SPECT-TTV vs. those patients with reduced SPECT-TTV and PSA (median 2.8 vs. 9.0 months P < 0.0001). Conclusion: Increasing PSMA SPECT-TTV on quantitative 177Lu-SPECT/CT predicts short progression free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify Lu-PSMA therapy.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 Sep 08 [Epub ahead of print]
Nikeith John, Sarennya Pathmanandavel, Megan Crumbaker, William Counter, Bao Ho, Andrew O Yam, Peter Wilson, Remy Niman, Maria Ayers, Aron Poole, Adam Hickey, Shikha Agrawal, Gary Perkins, Annukka Kallinen, Enid Eslick, Martin R Stockler, Anthony M Joshua, Andrew Nguyen, Louise Emmett
Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Australia., St. Vincent's Clinical School, University of New South Wales., MIM Software, Inc. Cleveland, Ohio, U.S.A., NHMRC Clinical Trials Centre, University of Sydney.