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Peer-reviewedCC BY 4.0Cancers

Prognostic Value of Baseline High-Uptake PSMA Tumor Volume Fraction in Metastatic Castration-Resistant Prostate Cancer Patients Treated with [177Lu]Lu-PSMA Radioligand Therapy

  • Marco Cuzzocrea1
  • Giovanna Pecoraro2,3,4
  • Cesare Michele Iacovitti1
  • Chiara Martinello1
  • Giorgio Treglia1,5,6
  • Silke Gillessen2,5
  • Martino Pedrani2
  • Gaetano Paone1,5
6 affiliations
  1. 1Clinic for Nuclear Medicine, Institute of Integrated Diagnostics of Southern Switzerland (IDISI), Ente Ospedaliero Cantonale (EOC), 6500 Bellinzona, Switzerland
  2. 2Department of Medical Oncology, Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), 6500 Bellinzona, Switzerland
  3. 3Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland
  4. 4Clinical and Translational Oncology (CTO), Scuola Superiore Meridionale, 80134 Naples, Italy
  5. 5Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland
  6. 6Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland
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Abstract

Background/Objectives: Lutetium-177 prostate-specific membrane antigen radioligand therapy ([177Lu]Lu-PSMA-RLT) is an effective treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), but no validated PSMA-PET/CT-based biomarker currently identifies patients at risk of early treatment failure. The aim of this study was to assess whether semi-quantitative PSMA-PET/CT parameters, in particular the fraction of PSMA-positive tumor volume with high uptake, are associated with early biochemical progression (EBP) and PSA50 response and secondarily with PSA-PFS and OS. Methods: Semiquantitative PSMA-PET parameters comprised reference lesion SUVmax (RL-SUVmax), SUVmean, total PSMA tumor volume (tPSMA-TV), tPSMA-TV above a fixed SUV threshold of 20 (tPSMA-TV20), the percentage of tPSMA-TV20 within tPSMA-TV (tPSMA-TV%), total lesion quotient (TLQ), TLQ20, and rTLQ%. The co-primary endpoints were EBP, defined as PSA progression according to the PCWG3 criteria within 4 months of the start of treatment, and PSA50 response, defined as a reduction in PSA of at least 50% compared with baseline. PSA-PFS (PCWG3-defined PSA progression or death from any cause) and OS were secondary endpoints. Results: 63 patients were retrospectively included (median follow-up, 20.9 months). In univariable analyses, higher baseline tPSMA-TV% was significantly associated with lower odds of EBP (OR per 10% increase, 0.71; 95% CI, 0.57–0.87; p = 0.001) and higher odds of PSA50 response (OR, 1.31; 95% CI, 1.07–1.61; p = 0.009). It was associated with longer PSA-PFS (HR, 0.75; 95% CI, 0.67–0.84; p < 0.001) and longer OS (HR, 0.81; 95% CI, 0.72–0.91; p < 0.001). Exploratory ROC analysis identified a tPSMA-TV% cut-off of 47.54% for EBP (AUC, 0.73 [95% CI, 0.57–0.86]; sensitivity, 0.61; specificity, 0.93), although this threshold requires external validation. In exploratory models including tPSMA-TV and SUVmean, tPSMA-TV% remained associated with PSA-PFS and OS but not with EBP or PSA50 response. Conclusions: Baseline tPSMA-TV% was associated with EBP, PSA50 response, PSA-PFS and OS in mCRPC patients undergoing [177Lu]Lu-PSMA-RLT, and these associations remained after adjustment for baseline PSA and metastatic presentation. tPSMA-TV% is a candidate prognostic imaging biomarker that requires external validation.

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Cite

BibTeXRIS
BibTeX
@article{cuzzocrea2026prognostic,
  title = {{Prognostic Value of Baseline High-Uptake PSMA Tumor Volume Fraction in Metastatic Castration-Resistant Prostate Cancer Patients Treated with [177Lu]Lu-PSMA Radioligand Therapy}},
  author = {Marco Cuzzocrea and Giovanna Pecoraro and Cesare Michele Iacovitti and Chiara Martinello and Giorgio Treglia and Silke Gillessen and Martino Pedrani and Gaetano Paone},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18203297},
  url = {https://www.mdpi.com/2072-6694/18/20/3297},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Prognostic Value of Baseline High-Uptake PSMA Tumor Volume Fraction in Metastatic Castration-Resistant Prostate Cancer Patients Treated with [177Lu]Lu-PSMA Radioligand Therapy
AU  - Marco Cuzzocrea
AU  - Giovanna Pecoraro
AU  - Cesare Michele Iacovitti
AU  - Chiara Martinello
AU  - Giorgio Treglia
AU  - Silke Gillessen
AU  - Martino Pedrani
AU  - Gaetano Paone
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18203297
UR  - https://www.mdpi.com/2072-6694/18/20/3297
AB  - Background/Objectives: Lutetium-177 prostate-specific membrane antigen radioligand therapy ([177Lu]Lu-PSMA-RLT) is an effective treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), but no validated PSMA-PET/CT-based biomarker currently identifies patients at risk of early treatment failure. The aim of this study was to assess whether semi-quantitative PSMA-PET/CT parameters, in particular the fraction of PSMA-positive tumor volume with high uptake, are associated with early biochemical progression (EBP) and PSA50 response and secondarily with PSA-PFS and OS. Methods: Semiquantitative PSMA-PET parameters comprised reference lesion SUVmax (RL-SUVmax), SUVmean, total PSMA tumor volume (tPSMA-TV), tPSMA-TV above a fixed SUV threshold of 20 (tPSMA-TV20), the percentage of tPSMA-TV20 within tPSMA-TV (tPSMA-TV%), total lesion quotient (TLQ), TLQ20, and rTLQ%. The co-primary endpoints were EBP, defined as PSA progression according to the PCWG3 criteria within 4 months of the start of treatment, and PSA50 response, defined as a reduction in PSA of at least 50% compared with baseline. PSA-PFS (PCWG3-defined PSA progression or death from any cause) and OS were secondary endpoints. Results: 63 patients were retrospectively included (median follow-up, 20.9 months). In univariable analyses, higher baseline tPSMA-TV% was significantly associated with lower odds of EBP (OR per 10% increase, 0.71; 95% CI, 0.57–0.87; p = 0.001) and higher odds of PSA50 response (OR, 1.31; 95% CI, 1.07–1.61; p = 0.009). It was associated with longer PSA-PFS (HR, 0.75; 95% CI, 0.67–0.84; p < 0.001) and longer OS (HR, 0.81; 95% CI, 0.72–0.91; p < 0.001). Exploratory ROC analysis identified a tPSMA-TV% cut-off of 47.54% for EBP (AUC, 0.73 [95% CI, 0.57–0.86]; sensitivity, 0.61; specificity, 0.93), although this threshold requires external validation. In exploratory models including tPSMA-TV and SUVmean, tPSMA-TV% remained associated with PSA-PFS and OS but not with EBP or PSA50 response. Conclusions: Baseline tPSMA-TV% was associated with EBP, PSA50 response, PSA-PFS and OS in mCRPC patients undergoing [177Lu]Lu-PSMA-RLT, and these associations remained after adjustment for baseline PSA and metastatic presentation. tPSMA-TV% is a candidate prognostic imaging biomarker that requires external validation.
SN  - 2072-6694
ER  -