Any decline in prostate‐specific antigen levels identifies survivors scheduled for prostate‐specific membrane antigen‐directed radioligand therapy

Purpose The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. Methods This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2–9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). Results After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1–5) and 2 (1–6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). Conclusion In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.

show abstract

“…Clinical outcome data were retrieved from the hospital medical records. The cohort has been partially described in [ 23 – 28 ].…”

Section: Methodsmentioning

confidence: 99%

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

Cytawa

Hendel

Tomasik

et al. 2023

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

show abstract

“…All patients gave written informed consent for the conducted procedures. Parts of this cohort have previously been reported (24)(25)(26)(27)(28), without focusing on fat-related and body composition parameters and their predictive performance for OS.…”

Section: Patient Cohortmentioning

confidence: 99%

Elevated Body Mass Index Is Associated with Improved Overall Survival in Castration-Resistant Prostate Cancer Patients Undergoing Prostate-Specific Membrane Antigen–Directed Radioligand Therapy

et al. 2023

Self Cite

View full text Add to dashboard Cite

In patients with prostate cancer scheduled for systemic treatment, being overweight is linked to prolonged overall survival (OS), whereas sarcopenia is associated with shorter OS. We investigated fat-related and body composition parameters in patients undergoing prostatespecific membrane antigen (PSMA)-directed radioligand therapy (RLT) to assess their predictive value for OS. Methods: Body mass index (BMI, in kg/m 2 ) and CT-derived body composition parameters (total, subcutaneous, visceral fat area, and psoas muscle area at the L3-L4 level) were determined for 171 patients scheduled for PSMAdirected RLT. After normalization for stature, the psoas muscle index was used to define sarcopenia. Outcome analysis was performed using Kaplan-Meier curves and Cox regression including fat-related and other clinical parameters (Gleason score, C-reactive protein [CRP], lactate dehydrogenase [LDH], hemoglobin, and prostatespecific antigen levels). The Harrell C-index was used for goodnessof-fit analysis. Results: Sixty-five patients (38%) had sarcopenia, and 98 patients (57.3%) had increased BMI. Relative to the 8-mo OS in normal-weight men (BMI , 25), overweight men (25 $ BMI . 30) and obese men (BMI $ 30) achieved a longer OS of 14 mo (hazard ratio [HR], 0.63; 95% CI, 0.40-0.99; P 5 0.03) and 13 mo (HR, 0.47; 95% CI, 0.29-0.77; P 5 0.004), respectively. Sarcopenia showed no impact on OS (11 vs. 12 mo; HR, 1.4; 95% CI, 0.91-2.1; P 5 0.09). Most of the body composition parameters were tightly linked to OS on univariable analyses, with the highest C-index for BMI. In multivariable analysis, a higher BMI (HR, 0.91; 95% CI, 0.86-0.97; P 5 0.006), lower CRP (HR, 1.09; 95% CI, 1.03-1.14; P , 0.001), lower LDH (HR, 1.08; 95% CI, 1.03-1.14; P , 0.001), and longer interval between initial diagnosis and RLT (HR, 0.95; 95% CI, 0.91-0.99; P 5 0.02) were significant predictors of OS. Conclusion: Increased fat reserves assessed by BMI, CRP, LDH, and interval between initial diagnosis and RLT, but not CT-derived body composition parameters, were relevant predictors for OS. As BMI can be altered, future research should investigate whether a high-calorie diet before or during PSMA RLT may improve OS.

show abstract

SUVmean on baseline [18F]PSMA-1007 PET and clinical parameters are associated with survival in prostate cancer patients scheduled for [177Lu]Lu-PSMA I&T

Hartrampf

Hüttmann

Seitz

et al. 2023

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

Background Quantification of [68 Ga]-labeled PSMA PET predicts response in patients with prostate cancer (PC) who undergo PSMA-targeted radioligand therapy (RLT). Given the increasing use [18F]-labeled radiotracers, we aimed to determine whether the uptake derived from [18F]PSMA-1007 PET can also identify responders and to assess its prognostic value relative to established clinical parameters. Methods We retrospectively analyzed 103 patients with metastatic, castration-resistant PC who were treated with [177Lu]Lu-PSMA I&T. We calculated SUVmean, SUVmax, PSMA-avid tumor volume (TV), and total lesion PSMA (defined as PSMA-TV*SUVmean) on pre-therapeutic [18F]PSMA-1007 PET. Laboratory values for hemoglobin, C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alkaline phosphatase (AP) were also collected prior to RLT. We performed univariable Cox regression followed by multivariable and Kaplan–Meier analyses with overall survival (OS) serving as endpoint. Last, we also computed a risk factor (RF) model including all items reaching significance on multivariable analysis to determine whether an increasing number of RFs can improve risk stratification. Results A total of 48 patients died and median OS was 16 months. On univariable Cox regression, SUVmean, CRP, LDH, hemoglobin, and the presence of liver metastases were significantly associated with OS. On multivariable Cox regression, the following significant prognostic factors for OS were identified: SUVmean (per unit, HR, 0.91; P = 0.04), the presence of liver metastases (HR, 2.37; P = 0.03), CRP (per mg/dl, HR, 1.13; P = 0.003), and hemoglobin (per g/dl, HR, 0.76; P < 0.01). Kaplan–Meier analysis showed significant separation between patients with a SUVmean below or above a median SUVmean of 9.4 (9 vs 19 months, HR 0.57; P = 0.03). Of note, patients with only one RF (median OS not reached) showed longest survival compared to patients with two (11 months; HR 2.43 95% CI 1.07–5.49, P = 0.02) or more than two RFs (7 months; HR 3.37 95% CI 1.62–7.03, P < 0.001). Conclusion A lower SUVmean derived from [18F]PSMA-1007, higher CRP, lower hemoglobin, and the presence of liver metastases are associated with reduced OS in patients undergoing RLT. An early RF model also demonstrated that an increasing number of those factors is linked to worse outcome, thereby emphasizing the importance of clinical and imaging parameters for adequate risk stratification.

show abstract

Any decline in prostate‐specific antigen levels identifies survivors scheduled for prostate‐specific membrane antigen‐directed radioligand therapy

Cited by 6 publications

References 13 publications

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

Elevated Body Mass Index Is Associated with Improved Overall Survival in Castration-Resistant Prostate Cancer Patients Undergoing Prostate-Specific Membrane Antigen–Directed Radioligand Therapy

SUVmean on baseline [18F]PSMA-1007 PET and clinical parameters are associated with survival in prostate cancer patients scheduled for [177Lu]Lu-PSMA I&T

Contact Info

Product

Resources

About