Total tumor volume complete response (TTV CR) on single-photon emission computed tomography/computed tomography (SPECT/CT) six weeks after combination treatment with enzalutamide and the theranostic 177Lu-PSMA-617 may be predictive of long-term survival in patients with metastatic castration-resistant prostate cancer (mCRPC).
For the study, a secondary analysis of the prospective multicenter ENZA-p trial, researchers reviewed SPECT/CT data and prostate-specific antigen (PSA) levels for 74 men (median age of 71) who had initial treatment fir mCRPC and a second treatment course of enzalutamide and 177Lu-PSMA-617 (Pluvicto, Novartis) at six weeks. The study authors noted that imaging was obtained 24 hours after each treatment course.
The researchers found that patients who had a TTV CR — defined as TTV less than 1 mL after the second treatment course — on SPECT/CT at six weeks had an 83 percent survival rate at two years in contrast to 67 percent for people who did not have a TTV CR at six weeks.
However, TTV CR assessment on prostate-specific membrane antigen positron emission tomography (PSMA PET) at 12 weeks showed no statistically significant impact on two-year survival rates, according to the study authors.
“This finding suggests that early TTV CR at SPECT/CT could serve as an alternative to interim PSMA PET/CT–derived CR for guiding adaptive dosing and deintensification treatment regimens for PSMA radioligand therapy,” noted lead study author Narjess Ayati, MD, who is affiliated with the Department of Theranostics and Nuclear Medicine at St. Vincent’s Hospital in Sydney, Australia, and colleagues.
A deep PSA response, which was defined as a > 90 percent decrease in PSA level at the second treatment course, occurred in 63 percent of patients, according to the study authors.
Three Key Takeaways
• Early SPECT/CT response predicts survival. A total tumor volume complete response (TTV CR < 1 mL) at 6 weeks on SPECT/CT after enzalutamide plus ¹⁷⁷Lu-PSMA-617 was associated with improved 2-year survival (83 percent vs. 67 percent), supporting early SPECT/CT imaging as a prognostic biomarker in mCRPC.
• SPECT/CT may outperform interim PSMA PET for response assessment. TTV CR on PSMA PET at 12 weeks did not correlate with survival, suggesting early SPECT/CT could be more clinically useful for guiding adaptive dosing or treatment de-intensification strategies.
• Complementary value of imaging and PSA kinetics. While deep PSA responses (>90 percent decline) were common and strongly associated with TTV CR, patients with PSA response without TTV CR had worse survival, highlighting that SPECT/CT can detect residual, potentially non–PSA-secreting disease and should be integrated with PSA evaluation for more accurate treatment assessment.
Ninety-two percent of patients with a TTV CR at six weeks had a deep PSA response. However, the researchers noted that those with a deep PSA response and no TTV CR at six weeks had a lower two-year survival rate of 76 percent, which declined to 54 percent for patients without TTV CR nor a deep PSA response.
“This finding is likely due to 177Lu-PSMA-617 SPECT/CT revealing persistent clonal populations that may be non-PSA-secretory, representing a subgroup of patients who may benefit from continued treatment with PSMA radioligand despite deep PSA response. This complementary interplay of biomarkers supports an integrated approach in which SPECT/CT is used to identify heterogenous disease burden that may not be reflected by PSA kinetics alone,” posited Ayati and colleagues.
(Editor’s note: For related content, see “New Study Shows High Efficacy and Patient Tolerance with 177Lu-PSMA-617 in Older Men with mCRPC,” “Could Pluvicto Be a First-Line Systemic Treatment for Patients with Oligometastatic Hormone-Sensitive PCa?” and “New PSMA PET Research Shows Merits of Pluvicto in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).”)
In regard to study limitations, the authors acknowledged the small cohort size and the use of labor-intensive quantitative proprietary software that isn’t commonly available in clinical practice.
