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Updated: Sep 4, 2025

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mCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients

Philipp E Hartrampf1, Ralph A Bundschuh2, Franz-Xaver Weinzierl1

  • 1Department of Nuclear Medicine, University Hospital Wuerzburg, Oberdürrbacherstraße Str. 6, 97080, Würzburg, Germany.

European Journal of Nuclear Medicine and Molecular Imaging
|July 19, 2022
PubMed
Summary

In metastatic castration-resistant prostate cancer (mCRPC) patients undergoing prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), a sustained decrease in prostate-specific antigen (PSA) levels correlates with longer overall survival (OS). Transient PSA fluctuations during RLT do not significantly impact survival outcomes compared to sustained decreases.

Keywords:
Flare phenomenonLate responsePSAPSMAProstate cancerRadioligand therapy

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Urology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) requires effective treatment strategies.
  • Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a key therapeutic modality for mCRPC.
  • Monitoring biochemical response via prostate-specific antigen (PSA) levels is crucial during RLT.

Purpose of the Study:

  • To evaluate the association between prostate-specific antigen (PSA) level dynamics and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA-targeted radioligand therapy (RLT).
  • To determine if sustained increases, decreases, or fluctuations in PSA levels during RLT predict different survival outcomes.

Main Methods:

  • A bicentric study included 176 mCRPC patients treated with PSMA-directed RLT.
  • PSA levels were measured at baseline and during RLT cycles.
  • Kaplan-Meier curves and log-rank tests were used to compare OS based on PSA level trends (sustained increase, decrease, or fluctuations).

Main Results:

  • A sustained PSA decrease was observed in 48.8% of patients, a sustained increase in 34.7%, and fluctuations in 16.5%.
  • Median OS was significantly longer for patients with sustained PSA decrease (19 months) compared to sustained PSA increase (8 months).
  • Patients with PSA fluctuations had a median OS of 18 months, comparable to those with sustained PSA decrease and significantly longer than those with sustained PSA increase.

Conclusions:

  • Sustained PSA decrease during RLT is associated with prolonged overall survival in mCRPC patients.
  • PSA fluctuations during RLT do not significantly worsen survival outcomes and should not necessitate treatment discontinuation without radiological progression.
  • Monitoring PSA dynamics provides valuable prognostic information for patients undergoing PSMA-targeted RLT.