Next Article in Journal
Emerging Biomarkers and Advanced Diagnostics in Chronic Kidney Disease: Early Detection Through Multi-Omics and AI
Next Article in Special Issue
Comparative Study of Cell Nuclei Segmentation Based on Computational and Handcrafted Features Using Machine Learning Algorithms
Previous Article in Journal
Evaluation of Optimized Toluidine Blue Stain as an Alternative Stain for Rapid On-Site Evaluation (ROSE)
Previous Article in Special Issue
Comparing and Combining Artificial Intelligence and Spectral/Statistical Approaches for Elevating Prostate Cancer Assessment in a Biparametric MRI: A Pilot Study
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Diagnostics
Volume 15
Issue 10
10.3390/diagnostics15101224
diagnostics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Detection Rates of PSMA-PET Radiopharmaceuticals in Recurrent Prostate Cancer: A Systematic Review

by
Soroush Rais-Bahrami
1,2,3,*,
Phillip Davis
4,
Albert Chau
5,
Samuel J. Galgano
2,
Brian F. Chapin
6,
David M. Schuster
7 and
Catriona M. Turnbull
5
1
Department of Urology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
3
O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
4
Blue Earth Diagnostics Inc., Needham, MA 02494, USA
5
Blue Earth Diagnostics Ltd., Oxford OX4 4GA, UK
6
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
7
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA
*
Author to whom correspondence should be addressed.
Diagnostics 2025, 15(10), 1224; https://doi.org/10.3390/diagnostics15101224
Submission received: 24 April 2025 / Revised: 9 May 2025 / Accepted: 11 May 2025 / Published: 13 May 2025
(This article belongs to the Special Issue Diagnostic Imaging of Prostate Cancer)
Browse Figures
Review Reports Versions Notes

Abstract

:
Background/Objectives: To conduct a systematic review to evaluate the detection rates (DR) of the three FDA-approved PSMA-targeted radiopharmaceuticals in patients with recurrent prostate cancer. Methods: Two individuals systematically searched MEDLINE, ScienceDirect, and Cochrane Libraries (February 2025), and independently reviewed all results to identify studies reporting patient-level 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat DR in ≥100 evaluable patients with recurrent prostate cancer. Sample-weighted means (SWM) of extracted DR were calculated. Results: Of 5059 published articles, 37 met our inclusion criteria, reporting data from 8843 patients undergoing 68Ga-PSMA-11 (n = 27), 18F-DCFPyL (n = 8), or 18F-flotufolastat (n = 2) studies. Heterogeneity was noted across enrolled populations, particularly in prior treatments. 68Ga-PSMA-11 studies recruited patients with marginally higher median PSA than 18F-DCFPyL or 18F-flotufolastat studies (median PSA ranged from 0.1 to 10.7, 0.2–2.5, and 0.6–1.1, respectively). Reported overall DR ranged from 25 to 91% for 68Ga-PSMA-11, 49–86% for 18F-DCFPyL, and 73–83% for 18F-flotufolastat, with SWM of 71%, 66%, and 79%, respectively. Post-prostatectomy DR were reported in 18 articles, resulting in SWM DR of 58% for 68Ga-PSMA-11 (n = 12), 55% for 18F-DCFPyL (n = 4), and 76% for 18F-flotufolastat (n = 2). Among post-radiotherapy patients, SWM were 87% for 68Ga-PSMA-11 (n = 4), 90% for 18F-DCFPyL (n = 2), and 99% for 18F-flotufolastat (n = 1). SWM DR at PSA < 1 ng/mL were 53%, 42%, and 66% for 68Ga-PSMA-11 (n = 13), 18F-DCFPyL (n = 5), and 18F-flotufolastat (n = 2), respectively. Conclusions: Considerable heterogeneity exists across populations in studies of diagnostic PET radiopharmaceuticals. Despite a paucity of 18F-DCFPyL and 18F-flotufolastat studies compared with 68Ga-PSMA-11, the available data suggest that all three radiopharmaceuticals provide high overall DR in patients with biochemical recurrence of prostate cancer.

1. Introduction

Prostate cancer is the second most common cancer among men worldwide, with an estimated 299,010 new cases and 35,250 deaths in the United States in 2024 [1]. Despite recent advances in diagnosis and primary treatment, up to 53% of patients still experience biochemical recurrence, or rising serum prostate specific antigen (PSA) levels after primary, curative-intent therapy [2].
Early and accurate delineation of the location and extent of recurrent prostate cancer lesions with a sensitive imaging modality can help inform salvage therapy plans and improve patient outcomes [3]. In recent years, positron emission tomography (PET) with radiopharmaceuticals that target prostate-specific membrane antigen (PSMA) has become the mainstay for imaging patients with prostate cancer owing to its improved sensitivity and diagnostic performance compared with conventional imaging methods such as computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy [2,4].
Three radiopharmaceuticals (68Ga-PSMA-11, 18F-DCFPyL [18F-piflufolastat], and 18F-flotufolastat [18F-rhPSMA-7.3]) that target the PSMA receptor are US Food and Drug Administration (FDA)-approved for imaging patients with recurrent prostate cancer [5,6,7]. The two 18F-labeled radiopharmaceuticals (18F-DCFPyL and 18F-flotufolastat) are manufactured with use of a cyclotron and have a half-life of approximately 110 min, while the 68Ga-labeled agent, which requires the use of a generator, has a shorter half-life of 68 min [5,6,7]. All show similar biodistribution patterns, with the lacrimal and salivary glands, small bowel, liver, spleen, kidney and bladder being the normal organs typically showing the highest absorbed doses [5,6,7,8,9]. All three are renally excreted, but there is some evidence to indicate lower urinary activity of 18F-flotufolastat at the time of imaging compared with 68Ga-PSMA-11 and 18F-DCFPyL [10] which may result in improved image assessment. However, there are no direct head-to-head comparisons of the diagnostic performance of these three PSMA-targeted radiopharmaceuticals in the same patients with recurrent prostate cancer. Moreover, new FDA requirements have seen the introduction of novel endpoints for the assessment of new diagnostic imaging agents that were not utilized in trials of earlier approved agents [11]. As such, cross-study comparisons of primary endpoints can be challenging [12]. However, the overall patient-level detection rate, without verification of imaging findings, still represents one of the main endpoints traditionally reported in diagnostic imaging studies of prostate cancer. Therefore, we conducted a descriptive systematic literature review to evaluate the overall patient-level detection rates of the three FDA-approved PSMA-targeted radiopharmaceuticals in order to evaluate their performance in patients experiencing biochemical recurrence of prostate cancer following curative-intent treatment.

2. Materials and Methods

This systematic review adhered to the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines [13]. Meta-analysis was not possible therefore Synthesis Without Meta-analysis (SWiM) guidance [14] was followed. Scientific literature databases (MEDLINE, ScienceDirect, and Cochrane Libraries) were systematically searched in October 2023 and again in February 2025 as part of a wider review using the search terms detailed in Figure 1. Searches were limited to journal articles published in English in the preceding 10 years. All review articles, practice guidelines, case reports, editorials, and letters were excluded. Studies that reported data from fewer than 100 patients in the cohort of interest were excluded to avoid the variability in data from small sample sizes. We also excluded any studies that included patients with PSA persistence following primary therapy among their cohort of patients with biochemical recurrence. A minimum data requirement was for a patient-level 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat detection rate in 100 or more patients with biochemical recurrence of prostate cancer. All included studies had to either report this directly in the article, or to have included data from which it could be extrapolated.
Following removal of any duplicate articles, the search results were screened first based on the title and then on the abstract text outlined in Figure 1. The full text of all remaining articles was then reviewed to identify all reports meeting our pre-set criteria. Where multiple reports from the same study population were identified, the report with the largest population of interest was selected for review. Retrospective analyses that included whole or partial datasets already selected for inclusion were omitted. The article screening was performed by two independent evaluators, and any discrepancies were resolved by discussion with the wider author group. Manual searches of the reference lists of all included articles were conducted using the same screening process as above to seek further studies for inclusion.
The full text of all included studies was reviewed, and any patient-level 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat detection rates were extracted along with key data regarding patient baseline characteristics and clinical history for the cohort of interest. Any available data that allowed determination of patient-level detection rates among patients with low PSA values (<1 ng/mL) or stratified by initial therapy (post-prostatectomy or post-radiotherapy) were also extracted, along with any positive predictive value (PPV) estimates. Sample-weighted means were calculated to appropriately weigh the detection rate reported in each individual study by its sample (cohort) size.
Studies were assessed for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool which assesses studies based on four domains: patient selection, index test, reference standard, and the study flow and timing [15].

3. Results

3.1. Search Results

The literature searches identified 5059 unique articles. Of these articles, 37 articles met our inclusion criteria and were considered suitable for evaluation in this systematic review (Figure 1). Thirteen (35%) of the articles reported prospective studies, 23 (62%) reported retrospective studies, and one (2.7%) reported an ambispective study. In total, 27 (73%) articles reported data with 68Ga-PSMA-11 [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42], eight (22%) with 18F-DCFPyL [43,44,45,46,47,48,49,50], and two (5.4%) with 18F-flotufolastat [11,51].
Assessment of bias using the QUADAS-2 tool is summarized in Table 1. Patient selection and the index test methodology were broadly considered to be at low risk of bias, although some studies introduced limits on PSA levels or a requirement for negative conventional imaging which may have introduced a source of selection bias. When considering the reference standard domain, all studies were considered to have high risk. Histopathology, the gold standard for verification of positive PET scans was not routinely utilized.

3.2. Patient Populations

Table 2 summarizes the patient populations of the 37 studies reported by the articles included in our review. In total, data from 8843 patients with biochemical recurrence who were scanned with 68Ga-PSMA-11 (n = 6497), 18F-DCFPyL (n = 1715), or 18F-flotufolastat (n = 631) were evaluated across the 34 studies.
The inclusion criteria for defining biochemical recurrence were not well reported by many of the included articles. Twelve (32%) articles included no details on how patients were defined as having biochemical recurrence. Eleven (30%) indicated that inclusion was based on some level of PSA rise post-therapy, while the remaining 14 (38%) studies selected patients who met the RTOG-ASTRO Phoenix consensus criteria definition of biochemical recurrence [52].
Nineteen of the 34 studies (51%) reported the mean age of their cohort, and these ranged between 61 and 71 years. A median age of the cohort was reported for 15 of the studies (41%), ranging from 66 to 75 years, with the remainder of reports not including age data.
Median PSA levels were reported in 32/37 (86%) studies. These ranged from 0.1 to 10.7 ng/mL. 68Ga-PSMA-11 studies recruited patients with marginally higher median PSA levels than 18F-DCFPyL or 18F-flotufolastat studies; the reported median PSA ranged from 0.1 to 10.7 ng/mL for 68Ga-PSMA-11, 0.2–2.5 ng/mL for 18F-DCFPyL, and 0.6–1.1 ng/mL for 18F-flotufolastat.
Most of the evaluated cohorts comprised a mixed population of patients initially treated with radical prostatectomy and/or radiotherapy. Thirteen (35%) articles (ten 68Ga-PSMA-11, two 18F-DCFPyL and one 18F-flotufolastat) studied cohorts of post-prostatectomy patients only and two (5.4%; both 68Ga-PSMA-11) studied cohorts of only patients who had not undergone prostatectomy (Table 2). Taken together, across all the articles, approximately 78% of the evaluable patients had undergone radical prostatectomy prior to PSMA-PET. When stratifying this by radiopharmaceutical, approximately 76% of patients undergoing 68Ga-PSMA-11 PET, 79% undergoing 18F-DCFPyL PET, and 87% undergoing 18F-flotufolastat PET were post-prostatectomy.

3.3. Detection Rates

3.3.1. Overall Patient-Level Detection Rates

Across the 27 68Ga-PSMA-11 studies, the overall patient-level detection rate ranged from 25 to 91%. The overall patient-level detection rate ranged from 49 to 86% across the eight 18F-DCFPyL studies and from 73 to 83% for the two 18F-flotufolastat studies. The sample-weighted mean detection rates calculated across all studies are 71% for 68Ga-PSMA-11, 66% for 18F-DCFPyL, and 79% for 18F-flotufolastat (Figure 2). Breakdown of the detection rates by anatomical region was not consistently reported for all radiopharmaceuticals.

3.3.2. Patient-Level Detection Rates Stratified by Prior Treatment

Eighteen articles (49%; 12 68Ga-PSMA-11 [18,19,21,24,26,27,30,35,37,38,39,41], four 18F-DCFPyL [44,46,48,50] and two 18F-flotufolastat [11,51]) reported detection rate data for patients who had undergone radical prostatectomy. The overall patient-level detection rate among patients who had undergone radical prostatectomy ranged from 25 to 80% across the 12 68Ga-PSMA-11 studies, from 47 to 76% across the four 18F-DCFPyL studies, and from 73 to 78% across the two 18F-flotufolastat studies. The sample-weighted mean detection rates patients who had undergone radical prostatectomy are 58% for 68Ga-PSMA-11, 55% for 18F-DCFPyL, and 76% for 18F-flotufolastat as shown in Figure 3.
Fewer articles (n = 7 [19%]; four 68Ga-PSMA-11 [24,25,37,40], two 18F-DCFPyL [46,48], and one 18F-flotufolastat [11]) reported detection rate data for patients who had undergone primary radiotherapy. The overall patient-level detection rate among those who had undergone radiotherapy ranged from 67 to 97% across the four 68Ga-PSMA-11 studies, 89–92% across the two 18F-DCFPyL studies and was reported to be 99% in the only 18F-flotufolastat study. Sample-weighted mean detection rates for patients who had undergone radiotherapy calculated from these data are 87% for 68Ga-PSMA-11, 90% for 18F-DCFPyL, and 99% for 18F-flotufolastat as presented in Figure 3.

3.3.3. Patient-Level Detection Rates Stratified by PSA Levels

In total, 20 of the 37 (54%) included articles reported detection rate data for patients who had a prescan PSA level < 1 ng/mL. Of these, 13 reported 68Ga-PSMA-11 data [16,23,24,26,28,29,31,33,34,38,40,41,42], five 18F-DCFPyL data [43,44,46,47,48], and two 18F-flotufolastat data [11,51]. The overall patient-level detection rate among patients with a PSA level < 1 ng/mL ranged from 30 to 73% across the 13 68Ga-PSMA-11 studies, from 38 to 58% across the five 18F-DCFPyL studies, and from 64 to 68% across the two 18F-flotufolastat studies. The sample-weighted mean detection rates in patients with a PSA level < 1 ng/mL are 53% for 68Ga-PSMA-11, 42% for 18F-DCFPyL and 66% for 18F-flotufolastat as shown in Figure 4.
Figure 5 provides a summary of the sample-weighted mean detection rates of 68Ga-PSMA-11, 18F-DCFPyL and 18F-flotufolastat among patients with biochemical recurrence of prostate cancer to illustrate the impact of low PSA level and prior treatment.

3.4. Positive Predictive Values

Only four (11%) of the studies verified the PSMA-positive detections as true and false positive in order to estimate the patient-level PPV [11,17,28,47]. Three of these studies provided PPV estimates based on histopathological verification of PSMA-positive lesions and show the PPV to be 84% for 68Ga-PSMA-11 [28], 79–83% for 18F-DCFPyL [47], and 82% for 18F-flotufolastat [11]. The fourth study used a composite reference standard that comprised PSA- or radiological-response to treatment, confirmative histology, or correlative imaging to verify 68Ga-PSMA-11-positive lesions and reported a higher PPV estimate of 93% [17].

4. Discussion

The advent of PSMA-targeting PET radiopharmaceuticals has facilitated the localization of small lesions below the resolution of conventional imaging techniques, earlier in the recurrence timeline. To date, three PSMA-targeting PET radiopharmaceuticals have been FDA-approved for use in recurrent prostate cancer. We conducted a large-scale systematic literature review to evaluate evidence of their detection efficacy in patients with recurrent prostate cancer.
Our data show the overall patient-level detection rate to be high for all three PSMA-targeted radiopharmaceuticals, with sample-weighted mean detection rates ranging from 71% for 68Ga-PSMA-11, to 66% for 18F-DCFPyL, and 79% for 18F-flotufolastat. However, considerable heterogeneity was noted across the enrolled populations, which likely would have influenced the detection rates. For example, a patient’s PSA level is known to impact the detection rate of all three radiopharmaceuticals, with higher detection rates observed at higher PSA levels [23,47,53]. Our analysis highlights the variation in the median PSA levels of the enrolled cohorts, with a broader range of median PSA levels noted for 68Ga-PSMA-11 studies than for studies of the other two radiopharmaceuticals.
Currently, biochemical recurrence is defined using the RTOG-ASTRO Phoenix consensus criteria [52]. However, as noted previously by others, these criteria have limited sensitivity for identifying early relapse that may require treatment before the Phoenix PSA thresholds are met [25]. It is likely that these thresholds, which consider the limited sensitivity of conventional imaging techniques such as CT, MRI, and bone scintigraphy, need redefining in the PSMA era. As such, it is perhaps not surprising that only 38% of the evaluated studies selected patients who met the RTOG-ASTRO Phoenix consensus criteria definition of biochemical recurrence, with many opting for modifications of these instead.
Further variation in patient populations was noted in their prior treatments, with over half of the studies recruiting mixed populations of patients initially treated with radical prostatectomy and/or radiotherapy. Perhaps consistent with the observation of its lowest range of median PSA levels, a greater proportion of post-prostatectomy patients was noted for the 18F-flotufolastat studies than for the other radiopharmaceuticals.
Given these disparities in patient cohorts, we evaluated the patient-level detection rates in more homogenous populations by extracting any detection rate data stratified by patients’ prior treatment, or in patients with low (<1 ng/mL) PSA levels. When stratified by prior treatment, the sample-weighted mean data show high detection rates for each of the radiopharmaceuticals in post-radiotherapy patients, ranging from 87% for 68Ga-PSMA-11 to 99% for 18F-flotufolastat. As might be expected, lower rates were achieved in post-prostatectomy patients, ranging from 55% for 18F-DCFPyL to 76% for 18F-flotufolastat. Moreover, the sample-weighted mean data reveal that 18F-flotufolastat identified recurrence in two-thirds of patients with a PSA level < 1 ng/mL, compared with approximately half the patients scanned with 68Ga-PSMA-11 or just two-fifths with 18F-DCFPyL, with similarly low-level PSA recurrences.
The high detection rate of 18F-flotufolastat at low PSA levels has been noted previously [53], with the authors suggesting that its favorable biodistribution, with sustained plasma bioavailability and limited bladder activity at the point of imaging [10], offers a diagnostic advantage [53]. Furthermore, in contrast with other PSMA-targeted radiopharmaceuticals, 18F-flotufolastat shows high-affinity receptor binding and internalization which likely contribute to its high detection rate [54].
Aside from the heterogeneity noted across the patient populations of the included studies, the main limitation of these data is that the patient-level detection rate evaluated here provides the overall percent positivity of patients scanned with the PSMA-targeted radiopharmaceutical in question. These positive PET findings were not verified pathologically and so likely include a proportion of false positive findings along with the true positive results of imaging. As indicated by the QUADAS-2 assessment, the risk of bias in the reference standard domain is considered high. Typical of studies in patients with recurrent prostate cancer, there are multiple practical and ethical factors which limit histopathological verification of the PET findings, especially when the scan is negative. Moreover, histopathology is unlikely to accurately determine every site of metastatic disease. While some studies attempted to verify positive scans by a variety of methods including histopathology, conventional imaging, and PSA follow up monitoring in order to verify PSMA-positive lesions, only 11% of the included studies reported a PPV estimate. Moreover, as recently reported [55], the standard of truth methodology used to verify PSMA-PET findings substantially impacts estimates, which could impact cross-trial comparisons. However, our analysis did identify studies reporting patient-level PPV estimates for each of the three evaluated radiopharmaceuticals using the gold standard histopathological verification of PET-positive detections. These data show very similar PPV estimates for the three radiopharmaceuticals (84% for 68Ga-PSMA-11 [28], 79–83% for 18F-DCFPyL [47], and 82% for 18F-flotufolastat [11]), and so it might be assumed that for each radiopharmaceutical a similar proportion of PET-positive lesions will be verified as true positive on a patient-level.
Vastly more studies were available for 68Ga-PSMA-11 than for 18F-DCFPyL or 18F-flotufolastat, likely a reflection of 68Ga-PSMA-11 having the earliest FDA-approval date [5,6,7]. Only two studies were available for 18F-flotufolastat, with the majority of data coming from a phase 3 registration trial, which had more stringent inclusion parameters than some of the post-approval studies reported for the earlier approved agents. Our analysis included only studies with larger patient cohorts (≥ 100 patients) to avoid the variability in data from small sample sizes. However, the relative paucity of large scale 18F-DCFPyL and 18F-flotufolastat studies limit our findings and further systematic literature reviews are warranted at a later date.

5. Conclusions

Considerable heterogeneity exists across populations in studies of diagnostic PET radiopharmaceuticals. Although we note a relative paucity of 18F-DCFPyL and 18F-flotufolastat studies compared with 68Ga-PSMA-11, the available data suggest that all three radiopharmaceuticals have high detection rates when considering the alternative conventional imaging modalities that were most commonly used previously. Due to the inherent differences in inclusion criteria and heterogeneity amongst the studies, we cannot make any conclusions around comparative detection rates. Head-to-head trials would provide direct comparisons to determine potential superiority of any one PSMA-targeted radiopharmaceutical over another. Until such studies are performed, decisions to use a specific radiopharmaceutical will be likely be determined by access to these agents, ease of administration, and discretion of the ordering physicians.

Author Contributions

Conceptualization, C.M.T. and P.D.; methodology, A.C. and P.D.; formal analysis and interpretation, all authors; writing—original draft preparation, C.M.T.; writing—reviewing and editing, all authors. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

The data reported in this article are available from the corresponding author on reasonable request.

Acknowledgments

The authors would like to thank S Cusco for their contributions to the search strategy.

Conflicts of Interest

Soroush Rais-Bahrami reports a consulting or advisory relationship with Blue Earth Diagnostics Ltd., Intuitive Surgical, Progenics, Bayer Healthcare, GE Healthcare, Boston Scientific, and Tempus. Phillip Davis is an employee of Blue Earth Diagnostics Inc. Albert Chau is a contractor for Blue Earth Diagnostics Ltd. Samuel J. Galgano reports funding grants from Blue Earth Diagnostics Ltd. Brian F. Chapin reports a consulting or advisory relationship with Johnson and Johnson, Janssen, Merck, Pfizer, Blue Earth Diagnostics Ltd., Blue Earth Therapeutics Ltd., and Provepharm. David M. Schuster reports funding grants from Blue Earth Diagnostics Ltd., Nihon MediPhysics Co., Ltd., Telix Pharmaceuticals (US) Inc., Advanced Accelerator Applications USA Inc., Fujifilm Pharmaceuticals USA Inc., and Amgen Inc.; a consulting or advisory relationship with Global Medical Solutions Taiwan, Progenics Pharmaceuticals Inc., Heidelberg University, and DuChemBio Co., Ltd.; and speakers fees from School of Breast Oncology and PrecisCa. Catriona M. Turnbull is an employee of Blue Earth Diagnostics Ltd.

References

  1. Siegel, R.L.; Giaquinto, A.N.; Jemal, A. Cancer statistics, 2024. CA Cancer J. Clin. 2024, 74, 12–49. [Google Scholar] [CrossRef] [PubMed]
  2. Cornford, P.; Tilki, D.; van den Bergh, R.C.N.; Briers, E.; Erberli, D.; De Meerleer, G.; Santis, M.D.; Farolfi, A.; Gandaglia, G.; Gillessen, S.; et al. EAU—EANM—ESTRO—ESUR—ISUP—SIOG guidelines on prostate cancer. In EAU Guidelines Edn, Proceedings of the EAU Annual Congress, Paris, France, 5–8 April 2024; EAU: London, UK, 2024; ISBN 978-94-92671-23-3. [Google Scholar]
  3. Morgan, T.M.; Boorjian, S.A.; Buyyounouski, M.K.; Chapin, B.F.; Chen, D.Y.T.; Cheng, H.H.; Chou, R.; Jacene, H.A.; Kamran, S.C.; Kim, S.K.; et al. Salvage therapy for prostate cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and treatment decision-making at the time of suspected biochemical recurrence after radical prostatectomy. J. Urol. 2024, 211, 509–517. [Google Scholar] [CrossRef] [PubMed]
  4. NCCN. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 3.2024. 2024. Available online: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf (accessed on 8 May 2025).
  5. FDA. Highlights of Prescribing Information: PYLARIFY® (Piflufolastat F 18) Injection. 2021. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214793s000lbl.pdf (accessed on 8 May 2025).
  6. FDA. Highlights of Prescribing Information: Gallium Ga 68 PSMA-11 Injection. 2020. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212642s000lbl.pdf (accessed on 8 May 2025).
  7. FDA. Highlights of Prescribing Information: POSLUMA (Flotufolastat F 18) Injection. 2023. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216023s000lbl.pdf (accessed on 8 May 2025).
  8. Dietlein, M.; Kobe, C.; Kuhnert, G.; Stockter, S.; Fischer, T.; Schomäcker, K.; Schmidt, M.; Dietlein, F.; Zlatopolskiy, B.D.; Krapf, P.; et al. Comparison of [18F]DCFPyL and [68Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol. Imaging Biol. 2015, 17, 575–584. [Google Scholar] [CrossRef] [PubMed]
  9. Ferreira, G.; Iravani, A.; Hofman, M.S.; Hicks, R.J. Intra-individual comparison of 68Ga-PSMA-11 and 18F-DCFPyL normal-organ biodistribution. Cancer Imaging 2019, 19, 23. [Google Scholar] [CrossRef]
  10. Kuo, P.H.; Hermsen, R.; Penny, R.; Postema, E.J. Quantitative and qualitative assessment of urinary activity of 18F-flotufolastat-PET/CT in patients with prostate cancer: A post hoc analysis of the LIGHTHOUSE and SPOTLIGHT studies. Mol. Imaging Biol. 2024, 26, 53–60. [Google Scholar] [CrossRef]
  11. Jani, A.B.; Ravizzini, G.C.; Gartrell, B.A.; Siegel, B.A.; Twardowski, P.; Saltzstein, D.; Fleming, M.T.; Chau, A.; Davis, P.; Chapin, B.F.; et al. Diagnostic performance and safety of 18F-rhPSMA-7.3 PET in men with suspected prostate cancer recurrence: Results from a phase 3, prospective, multicenter study (SPOTLIGHT). J. Urol. 2023, 210, 299–311. [Google Scholar] [CrossRef]
  12. Jani, A.B.; Ravizzini, G.C.; Gartrell, B.A.; Siegel, B.A.; Twardowski, P.; Saltzstein, D.; Fleming, M.T.; Chau, A.; Davis, P.; Chapin, B.F.; et al. Reply by authors. J. Urol. 2023, 210, 310–311. [Google Scholar] [CrossRef]
  13. Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ 2009, 339, b2700. [Google Scholar] [CrossRef]
  14. Campbell, M.; McKenzie, J.E.; Sowden, A.; Katikireddi, S.V.; Brennan, S.E.; Ellis, S.; Hartmann-Boyce, J.; Ryan, R.; Shepperd, S.; Thomas, J.; et al. Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline. BMJ 2020, 368, l6890. [Google Scholar] [CrossRef]
  15. Whiting, P.F.; Rutjes, A.W.; Westwood, M.E.; Mallett, S.; Deeks, J.J.; Reitsma, J.B.; Leeflang, M.M.; Sterne, J.A.; Bossuyt, P.M. QUADAS-2: A revised tool for the quality assessment of diagnostic accuracy studies. Ann. Intern. Med. 2011, 155, 529–536. [Google Scholar] [CrossRef]
  16. Akdemir, E.N.; Tuncel, M.; Akyol, F.; Bilen, C.Y.; Baydar, D.E.; Karabulut, E.; Ozen, H.; Caglar, M. 68Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer. World J. Urol. 2019, 37, 813–821. [Google Scholar] [CrossRef] [PubMed]
  17. Alberts, I.; Mingels, C.; Zacho, H.D.; Lanz, S.; Schöder, H.; Rominger, A.; Zwahlen, M.; Afshar-Oromieh, A. Comparing the clinical performance and cost efficacy of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in the diagnosis of recurrent prostate cancer: A Markov chain decision analysis. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 4252–4261. [Google Scholar] [CrossRef] [PubMed]
  18. Armstrong, W.R.; Kishan, A.U.; Booker, K.M.; Grogan, T.R.; Elashoff, D.; Lam, E.C.; Clark, K.J.; Steinberg, M.L.; Fendler, W.P.; Hope, T.A.; et al. Impact of prostate-specific membrane antigen positron emission tomography/computed tomography on prostate cancer salvage radiotherapy management: Results from a prospective multicenter randomized phase 3 trial (PSMA-SRT NCT03582774). Eur. Urol. 2024, 86, 52–60. [Google Scholar] [CrossRef] [PubMed]
  19. Boreta, L.; Gadzinski, A.J.; Wu, S.Y.; Xu, M.; Greene, K.; Quanstrom, K.; Nguyen, H.G.; Carroll, P.R.; Hope, T.A.; Feng, F.Y. Location of recurrence by gallium-68 PSMA-11 PET scan in prostate cancer patients eligible for salvage radiotherapy. Urology 2019, 129, 165–171. [Google Scholar] [CrossRef]
  20. Brito, A.E.T.; Mourato, F.A.; de Oliveira, R.P.M.; Leal, A.L.G.; Filho, P.J.A.; de Filho, J.L.L. Evaluation of whole-body tumor burden with 68Ga-PSMA PET/CT in the biochemical recurrence of prostate cancer. Ann. Nucl. Med. 2019, 33, 344–350. [Google Scholar] [CrossRef]
  21. Burgard, C.; Hoffmann, M.A.; Frei, M.; Buchholz, H.-G.; Khreish, F.; Marlowe, R.J.; Schreckenberger, M.; Ezziddin, S.; Rosar, F. Detection efficacy of 68Ga-PSMA-11 PET/CT in biochemical recurrence of prostate cancer with very low PSA levels: A 7-year, two-center “real-world” experience. Cancers 2023, 15, 1376. [Google Scholar] [CrossRef]
  22. Caroli, P.; Sandler, I.; Matteucci, F.; De Giorgi, U.; Uccelli, L.; Celli, M.; Foca, F.; Barone, D.; Romeo, A.; Sarnelli, A.; et al. 68Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: Prospective results in 314 patients. Eur. J. Nucl. Med. Mol. Imaging 2018, 45, 2035–2044. [Google Scholar] [CrossRef]
  23. Cerci, J.J.; Fanti, S.; Lobato, E.E.; Kunikowska, J.; Alonso, O.; Medina, S.; Novruzov, F.; Lengana, T.; Granados, C.; Kumar, R.; et al. Diagnostic performance and clinical impact of 68Ga-PSMA-11 PET/CT imaging in early relapsed prostate cancer after radical therapy: A prospective multicenter study (IAEA-PSMA Study). J. Nucl. Med. 2022, 63, 240–247. [Google Scholar] [CrossRef]
  24. Christensen, M.T.; Jochumsen, M.R.; Klingenberg, S.; Sorensen, K.D.; Borre, M.; Bouchelouche, K. Evaluation of predictors of biochemical recurrence in prostate cancer patients, as detected by 68Ga-PSMA PET/CT. Diagnostics 2022, 12, 195. [Google Scholar] [CrossRef]
  25. Einspieler, I.; Rauscher, I.; Düwel, C.; Krönke, M.; Rischpler, C.; Habl, G.; Dewes, S.; Ott, A.; Wester, H.-J.; Schwaiger, M.; et al. Detection efficacy of hybrid 68Ga-PSMA ligand PET/CT in prostate cancer patients with biochemical recurrence after primary radiation therapy defined by Phoenix Criteria. J. Nucl. Med. 2017, 58, 1081–1087. [Google Scholar] [CrossRef]
  26. Emmett, L.; Tang, R.; Nandurkar, R.H.; Hruby, G.; Roach, P.J.; Watts, J.A.; Cusick, T.; Kneebone, A.; Ho, B.; Chan, L.; et al. 3-Year freedom from progression after 68Ga-PSMA PET/CT-triaged management in men with biochemical recurrence after radical prostatectomy: Results of a prospective multicenter trial. J. Nucl. Med. 2020, 61, 866–872. [Google Scholar] [CrossRef] [PubMed]
  27. Farolfi, A.; Ceci, F.; Castellucci, P.; Graziani, T.; Siepe, G.; Lambertini, A.; Schiavina, R.; Lodi, F.; Morganti, A.G.; Fanti, S. 68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA < 0.5 ng/mL. Efficacy and impact on treatment strategy. Eur. J. Nucl. Med. Mol. Imaging 2019, 46, 11–19. [Google Scholar] [CrossRef] [PubMed]
  28. Fendler, W.P.; Calais, J.; Eiber, M.; Flavell, R.R.; Mishoe, A.; Feng, F.Y.; Nguyen, H.G.; Reiter, R.E.; Rettig, M.B.; Okamoto, S.; et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: A prospective single-arm clinical trial. JAMA Oncol. 2019, 5, 856–863. [Google Scholar] [CrossRef]
  29. Fourquet, A.; Lahmi, L.; Rusu, T.; Belkacemi, Y.; Crehange, G.; de la Taille, A.; Fournier, G.; Cussenot, O.; Gauthé, M. Restaging the biochemical recurrence of prostate cancer with [68Ga]Ga-PSMA-11 PET/CT: Diagnostic performance and impact on patient disease management. Cancers 2021, 13, 1594. [Google Scholar] [CrossRef] [PubMed]
  30. Freitag, M.T.; Radtke, J.P.; Afshar-Oromieh, A.; Roethke, M.C.; Hadaschik, B.; Gleave, M.; Bonekamp, D.; Kopka, K.; Eder, M.; Heusser, T.; et al. Local recurrence of prostate cancer after radical prostatectomy is at risk to be missed in 68Ga-PSMA-11-PET of PET/CT and PET/MRI: Comparison with mpMRI integrated in simultaneous PET/MRI. Eur. J. Nucl. Med. Mol. Imaging 2017, 44, 776–787. [Google Scholar] [CrossRef]
  31. Hamed, M.A.G.; Basha, M.A.A.; Ahmed, H.; Obaya, A.A.; Afifi, A.H.M.; Abdelbary, E.H. 68Ga-PSMA PET/CT in patients with rising prostatic-specific antigen after definitive treatment of prostate cancer: Detection efficacy and diagnostic accuracy. Acad. Radiol. 2019, 26, 450–460. [Google Scholar] [CrossRef]
  32. Hoffmann, M.A.; Buchholz, H.-G.; Wieler, H.J.; Müller-Hübenthal, J.; Trampert, L.; Richardsen, I.; Schreckenberger, M. Diagnostic performance of 68Ga-PSMA-11 positron-emission-tomography/computed-tomography in a large cohort of patients with biochemical recurrence of prostate carcinoma. Health Phys. 2020, 119, 141–147. [Google Scholar] [CrossRef]
  33. Lawal, I.O.; Lengana, T.; Popoola, G.O.; Orunmuyi, A.T.; Kgatle, M.M.; Mokoala, K.M.G.; Sathekge, M.M. Pattern of prostate cancer Recurrence assessed by 68Ga-PSMA-11 PET/CT in men treated with primary local therapy. J. Clin. Med. 2021, 10, 3883. [Google Scholar] [CrossRef]
  34. McCarthy, M.; Francis, R.; Tang, C.; Watts, J.; Campbell, A. A multicenter prospective clinical trial of 68Gallium PSMA HBED-CC PET-CT restaging in biochemically relapsed prostate carcinoma: Oligometastatic rate and distribution compared with standard imaging. Int. J. Radiat. Oncol. Biol. Phys. 2019, 104, 801–808. [Google Scholar] [CrossRef]
  35. Miksch, J.; Bottke, D.; Krohn, T.; Thamm, R.; Bartkowiak, D.; Solbach, C.; Bolenz, C.; Beer, M.; Wiegel, T.; Beer, A.J.; et al. Interobserver variability, detection rate, and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 2339–2347. [Google Scholar] [CrossRef]
  36. Müller, J.; Ferraro, D.A.; Muehlematter, U.J.; Schüler, H.I.G.; Kedzia, S.; Eberli, D.; Guckenberger, M.; Kroeze, S.G.C.; Sulser, T.; Schmid, D.M.; et al. Clinical impact of 68Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction. Eur. J. Nucl. Med. Mol. Imaging 2019, 46, 889–900. [Google Scholar] [CrossRef] [PubMed]
  37. Pinot, F.; Le Pennec, R.; Abgral, R.; Blanc-Béguin, F.; Hennebicq, S.; Schick, U.; Valeri, A.; Fournier, G.; Le Roux, P.-Y.; Salaun, P.-Y.; et al. PSMA-11 PET/CT for detection of recurrent prostate cancer in patients with negative choline PET/CT. Clin. Genitourin. Cancer 2023, 21, 248–257. [Google Scholar] [CrossRef] [PubMed]
  38. Rauscher, I.; Düwel, C.; Haller, B.; Rischpler, C.; Heck, M.M.; Gschwend, J.E.; Schwaiger, M.; Maurer, T.; Eiber, M. Efficacy, predictive factors, and prediction nomograms for 68Ga-labeled prostate-specific membrane antigen-ligand positron-emission tomography/computed tomography in early biochemical recurrent prostate cancer after radical prostatectomy. Eur. Urol. 2018, 73, 656–661. [Google Scholar] [CrossRef]
  39. Rauscher, I.; Kroenke, M.; König, M.; Gafita, A.; Maurer, T.; Horn, T.; Schiller, K.; Weber, W.; Eiber, M. Matched-pair comparison of 68Ga-PSMA-11 and 18F-PSMA-1007 PET/CT: Frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J. Nucl. Med. 2020, 61, 51–57. [Google Scholar] [CrossRef]
  40. Raveenthiran, S.; Yaxley, J.; Gianduzzo, T.; Kua, B.; McEwan, L.; Wong, D.; Tsang, G.; MacKean, J. The use of 68Ga-PET/CT PSMA to determine patterns of disease for biochemically recurrent prostate cancer following primary radiotherapy. Prostate Can. Prostate Dis. 2019, 22, 385–390. [Google Scholar] [CrossRef]
  41. Seniaray, N.; Verma, R.; Khanna, S.; Belho, E.; Pruthi, A.; Mahajan, H. Localization and restaging of carcinoma prostate by 68Gallium prostate-specific membrane antigen positron emission tomography computed tomography in patients with biochemical recurrence. Indian J. Urol. 2020, 36, 191–199. [Google Scholar] [CrossRef]
  42. Verburg, F.A.; Pfister, D.; Heidenreich, A.; Vogg, A.; Drude, N.I.; Vöö, S.; Mottaghy, F.M.; Behrendt, F.F. Extent of disease in recurrent prostate cancer determined by [68Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score. Eur. J. Nucl. Med. Mol. Imaging 2016, 43, 397–403. [Google Scholar] [CrossRef]
  43. Garcia-Zoghby, L.; Lucas-Lucas, C.; Amo-Salas, M.; Soriano-Castrejon, A.M.; Garcia-Vicente, A.M. Head-to-head comparison of [18F]F-choline and imaging of prostate-specific membrane antigen, using [18F]DCFPyL PET/CT, in patients with biochemical recurrence of prostate cancer. Curr. Oncol. 2023, 30, 6271–6288. [Google Scholar] [CrossRef]
  44. Li, E.V.; Bennett, R.; Ho, A.; Wong, C.; Mahenthiran, A.K.; Kumar, S.K.S.R.; Sun, Z.; Savas, H.; Rowe, S.P.; Schaeffer, E.M.; et al. Clinical factors associated with suspicious 18F-DCFPyL prostate-specific membrane antigen positron emission tomography activity in patients initially managed with radical prostatectomy including prostate-specific antigen < 0.5 ng/mL. J. Urol. 2025, 213, 183–191. [Google Scholar] [CrossRef]
  45. Meijer, D.; Jansen, B.H.E.; Wondergem, M.; Bodar, Y.J.L.; Srbljin, S.; Vellekoop, A.E.; Keizer, B.; van der Zant, F.M.; Hoekstra, O.S.; Nieuwenhuijzen, J.A.; et al. Clinical verification of 18F-DCFPyL PET-detected lesions in patients with biochemically recurrent prostate cancer. PLoS ONE 2020, 15, e0239414. [Google Scholar] [CrossRef]
  46. Mena, E.; Rowe, S.P.; Shih, J.H.; Lindenberg, L.; Turkbey, B.; Fourquet, A.; Lin, F.I.; Adler, S.; Eclarinal, P.; McKinney, Y.L.; et al. Predictors of 18F-DCFPyL PET/CT positivity in patients with biochemical recurrence of prostate cancer after local therapy. J. Nucl. Med. 2022, 63, 1184–1190. [Google Scholar] [CrossRef] [PubMed]
  47. Morris, M.J.; Rowe, S.P.; Gorin, M.A.; Saperstein, L.; Pouliot, F.; Josephson, D.; Wong, J.Y.; Pantel, A.R.; Cho, S.Y.; Gage, K.L.; et al. Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: Results from the CONDOR phase III, multicenter study. Clin. Cancer Res. 2021, 27, 3674–3682. [Google Scholar] [CrossRef] [PubMed]
  48. Oprea-Lager, D.-E.; Gontier, E.; García-Cañamaque, L.; Gauthé, M.; Olivier, P.; Mitjavila, M.; Tamayo, P.; Robin, P.; Vicente, A.M.G.; Bouyeure, A.-C.; et al. [18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in biochemical recurrence of prostate cancer (PYTHON): A prospective, open label, cross-over, comparative study. Eur. J. Nucl. Med. Mol. Imaging 2023, 50, 3439–3451. [Google Scholar] [CrossRef] [PubMed]
  49. Rousseau, E.; Wilson, D.; Lacroix-Poisson, F.; Krauze, A.; Chi, K.; Gleave, M.; McKenzie, M.; Tyldesley, S.; Goldenberg, S.L.; Bénard, F. A prospective study on 18F-DCFPyL PSMA PET/CT imaging in biochemical recurrence of prostate cancer. J. Nucl. Med. 2019, 60, 1587–1593. [Google Scholar] [CrossRef]
  50. Sigurdson, S.; al Salman, K.; Mesci, A.; Dayes, I.; Quan, K.; Goldberg, M.; Schnarr, K.; Shayegan, B.; Bauman, G.; Zukotynski, K.; et al. Patterns of failure with 18F-DCFPyL PSMA-PET/CT in the post-prostatectomy setting: A regional cohort analysis. Can. Urol. Assoc. J. 2024, 19, 17–24. [Google Scholar] [CrossRef]
  51. Rauscher, I.; Karimzadeh, A.; Schiller, K.; Horn, T.; D’alessandria, C.; Franz, C.; Wörther, H.; Nguyen, N.; Combs, S.E.; Weber, W.A.; et al. Detection efficacy of 18F-rhPSMA-7.3 PET/CT and impact on patient management in patients with biochemical recurrence of prostate cancer after radical prostatectomy and prior to potential salvage treatment. J. Nucl. Med. 2021, 62, 1719–1726. [Google Scholar] [CrossRef]
  52. Roach, M.; Hanks, G.; Thames, H.; Schellhammer, P.; Shipley, W.U.; Sokol, G.H.; Sandler, H. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int. J. Radiat. Oncol. Biol. Phys. 2006, 65, 965–974. [Google Scholar] [CrossRef]
  53. Lowentritt, B.H.; Jani, A.B.; Helfand, B.T.; Uchio, E.M.; Morris, M.A.; Michalski, J.M.; Chau, A.; Davis, P.; Chapin, B.F.; Schuster, D.M. Impact of clinical factors on 18F-flotufolastat detection rates in men with recurrent prostate cancer: Exploratory analysis of the phase 3 SPOTLIGHT Study. Adv. Rad. Oncol. 2024, 9, 101532. [Google Scholar] [CrossRef]
  54. Wurzer, A.; Di Carlo, D.; Schmidt, A.; Beck, R.; Eiber, M.; Schwaiger, M.; Wester, H.-J. Radiohybrid ligands: A novel tracer concept exemplified by 18F- or 68Ga-labeled rhPSMA-inhibitors. J. Nucl. Med. 2020, 61, 735–742. [Google Scholar] [CrossRef]
  55. Lowentritt, B.H.; Chau, A.; Davis, P. How standard of truth methodology impacts diagnostic PSMA-targeting radiopharmaceutical evaluation: Learnings from the Phase 3 SPOTLIGHT study. Diagnostics 2025, 15, 473. [Google Scholar] [CrossRef]
Diagnostics 15 01224 g001
Figure 1. PRISMA flow chart illustrating the systematic literature search process. * Excluded articles comprised review articles, practice guidelines, editorials, and letters. † Excluded study types included case studies, case series and preclinical evaluations. ‡ Excluded studies included those evaluating a radiopharmaceutical other than 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat, those focused on another cancer type, therapeutic studies, and any studies that included patients with PSA persistence following primary therapy among their cohort of patients with biochemical recurrence. § Any studies that reported data from fewer than 100 patients in the cohort of interest were excluded. The minimum data requirement for inclusion was for a patient-level 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat detection rate in 100 or more patients with biochemical recurrence of prostate cancer.
Figure 1. PRISMA flow chart illustrating the systematic literature search process. * Excluded articles comprised review articles, practice guidelines, editorials, and letters. † Excluded study types included case studies, case series and preclinical evaluations. ‡ Excluded studies included those evaluating a radiopharmaceutical other than 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat, those focused on another cancer type, therapeutic studies, and any studies that included patients with PSA persistence following primary therapy among their cohort of patients with biochemical recurrence. § Any studies that reported data from fewer than 100 patients in the cohort of interest were excluded. The minimum data requirement for inclusion was for a patient-level 68Ga-PSMA-11, 18F-DCFPyL, or 18F-flotufolastat detection rate in 100 or more patients with biochemical recurrence of prostate cancer.
Diagnostics 15 01224 g001
Diagnostics 15 01224 g002
Figure 2. Sample-weighted mean patient-level detection rates across the 27 68Ga-PSMA-11 studies, 8 18F-DCFPyL studies, and 2 18F-flotufolastat studies.
Figure 2. Sample-weighted mean patient-level detection rates across the 27 68Ga-PSMA-11 studies, 8 18F-DCFPyL studies, and 2 18F-flotufolastat studies.
Diagnostics 15 01224 g002
Diagnostics 15 01224 g003
Figure 3. Sample-weighted mean patient-level detection rates across the included studies stratified by prior treatment. Post-prostatectomy data (solid bars) were available for 12 68Ga-PSMA-11 studies, 4 18F-DCFPyL studies and 2 18F-flotufolastat studies. Post-radiotherapy data (hatched bars) were reported for 4 68Ga-PSMA-11 studies, 2 18F-DCFPyL studies, and 1 18F-flotufolastat study.
Figure 3. Sample-weighted mean patient-level detection rates across the included studies stratified by prior treatment. Post-prostatectomy data (solid bars) were available for 12 68Ga-PSMA-11 studies, 4 18F-DCFPyL studies and 2 18F-flotufolastat studies. Post-radiotherapy data (hatched bars) were reported for 4 68Ga-PSMA-11 studies, 2 18F-DCFPyL studies, and 1 18F-flotufolastat study.
Diagnostics 15 01224 g003
Diagnostics 15 01224 g004
Figure 4. Sample-weighted mean detection rates in patients with PSA levels < 1 ng/mL across the included studies. Detection rates among patients with PSA < 1 ng/mL were reported for 13 68Ga-PSMA-11 studies, 5 18F-DCFPyL studies, and 2 18F-flotufolastat studies.
Figure 4. Sample-weighted mean detection rates in patients with PSA levels < 1 ng/mL across the included studies. Detection rates among patients with PSA < 1 ng/mL were reported for 13 68Ga-PSMA-11 studies, 5 18F-DCFPyL studies, and 2 18F-flotufolastat studies.
Diagnostics 15 01224 g004
Diagnostics 15 01224 g005
Figure 5. Summary of sample-weighted mean detection rates and impact of low PSA and prior treatment.
Figure 5. Summary of sample-weighted mean detection rates and impact of low PSA and prior treatment.
Diagnostics 15 01224 g005
Table 1. Risk of bias appraisal of the included studies according to the QUADAS-2 tool.
Table 1. Risk of bias appraisal of the included studies according to the QUADAS-2 tool.
ArticleRisk of Bias
Patient SelectionIndex TestReference
Standard		Flow and
Timing
Akdemir, 2019 [16]LOWLOWHIGHHIGH
Alberts, 2022 [17]LOWLOWHIGHHIGH
Armstrong, 2024 [18]LOWLOWHIGHHIGH
Boreta, 2019 [19]LOWLOWHIGHHIGH
Brito, 2019 [20]LOWLOWHIGHHIGH
Burgard, 2023 [21]UNCLEARLOWHIGHHIGH
Caroli, 2018 [22]LOWLOWHIGHHIGH
Cerci, 2022 [23]UNCLEARLOWHIGHHIGH
Christensen, 2022 [24]LOWLOWHIGHHIGH
Einspieler, 2017 [25]LOWLOWHIGHHIGH
Emmett, 2020 [26]UNCLEARLOWHIGHHIGH
Farolfi, 2019 [27]UNCLEARLOWHIGHHIGH
Fendler, 2019 [28]LOWLOWHIGHHIGH
Fourquet, 2021 [29]LOWLOWHIGHHIGH
Freitag, 2017 [30]LOWLOWHIGHHIGH
Hamed, 2019 [31]LOWLOWHIGHHIGH
Hoffmann, 2020 [32]LOWLOWHIGHHIGH
Lawal, 2021 [33]UNCLEARLOWHIGHHIGH
McCarthy, 2019 [34]UNCLEARLOWHIGHHIGH
Miksch, 2020 [35]UNCLEARLOWHIGHHIGH
Müller, 2019 [36]LOWLOWHIGHHIGH
Pinot, 2023 [37]LOWLOWHIGHHIGH
Rauscher, 2018 [38]UNCLEARLOWHIGHHIGH
Rauscher, 2020 [39]LOWLOWHIGHHIGH
Raveenthiran, 2019 [40]LOWLOWHIGHHIGH
Seniaray, 2020 [41]LOWLOWHIGHHIGH
Verburg, 2016 [42]LOWLOWHIGHHIGH
García-Zoghby, 2023 [43]UNCLEARLOWHIGHHIGH
Li, 2025 [44]UNCLEARLOWHIGHHIGH
Meijer, 2020 [45]LOWLOWHIGHHIGH
Mena, 2022 [46]UNCLEARLOWHIGHHIGH
Morris, 2021 [47]UNCLEARLOWHIGHHIGH
Oprea-Lager, 2023 [48]LOWLOWHIGHHIGH
Rousseau, 2019 [49]LOWLOWHIGHHIGH
Sigurdson, 2024 [50]LOWLOWHIGHHIGH
Jani, 2023 [11]LOWLOWHIGHHIGH
Rauscher, 2021 [51]LOWLOWHIGHHIGH
Table 2. Patient characteristics and overall detection rates across the included studies.
Table 2. Patient characteristics and overall detection rates across the included studies.
ArticleRadiopharmaceutical EvaluatedNumber of Patients in the Relevant CohortMedian PSA, ng/mLOverall Patient-Level Detection Rate a, %Proportion of Patients Who Had Undergone Radical Prostatectomy, %
Akdemir, 2019 [16]68Ga-PSMA-111213.97647
Alberts, 2022 [17]68Ga-PSMA-111222.88779
Armstrong, 2024 [18]68Ga-PSMA-111020.238100
Boreta, 2019 [19]68Ga-PSMA-111250.453100
Brito, 2019 [20]68Ga-PSMA-111001.77269
Burgard, 2023 [21]68Ga-PSMA-111150.125100
Caroli, 2018 [22]68Ga-PSMA-113140.86384
Cerci, 2022 [23]68Ga-PSMA-111004NR (mean = 1.6)6578
Christensen, 2022 [24]68Ga-PSMA-1118910.55581
Einspieler, 2017 [25]68Ga-PSMA-111186.4910
Emmett, 2020 [26]68Ga-PSMA-112600.365100
Farolfi, 2019 [27]68Ga-PSMA-111190.334100
Fendler, 2019 [28]68Ga-PSMA-116352.17573
Fourquet, 2021 [29]68Ga-PSMA-11294NR (mean = 3.0)6986
Freitag, 2017 [30]68Ga-PSMA-111191.778100
Hamed, 2019 [31]68Ga-PSMA-111882.28838
Hoffmann, 2020 [32]68Ga-PSMA-1166010.77681
Lawal, 2021 [33]68Ga-PSMA-112472.78164
McCarthy, 2019 [34]68Ga-PSMA-112382.67764
Miksch, 2020 [35]68Ga-PSMA-11116NR (mean = 0.3)50100
Müller, 2019 [36]68Ga-PSMA-112231.07498
Pinot, 2023 [37]68Ga-PSMA-111590.86690
Rauscher, 2018 [38]68Ga-PSMA-112720.565100
Rauscher, 2020 [39]68Ga-PSMA-111020.980100
Raveenthiran, 2019 [40]68Ga-PSMA-112763.6860
Seniaray, 2020 [41]68Ga-PSMA-111241.870100
Verburg, 2016 [42]68Ga-PSMA-111554.08064
García-Zoghby, 2023 [43]18F-DCFPyL138NR (mean = 2.8)6557
Li, 2025 [44]18F-DCFPyL4150.449100
Meijer, 2020 [45]18F-DCFPyL2622.58648
Mena, 2022 [46]18F-DCFPyL2451.67980
Morris, 2021 [47]18F-DCFPyL2080.86285
Oprea-Lager, 2023 [48]18F-DCFPyL2010.55873
Rousseau, 2019 [49]18F-DCFPyL130NR (mean = 5.2)8572
Sigurdson, 2024 [50]18F-DCFPyL1160.252100
Jani, 2023 [11]18F-Flotufolastat3891.18379
Rauscher, 2021 [51]18F-Flotufolastat2420.673100
a Either reported directly or extrapolated from data included in the article. NR, not reported.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Rais-Bahrami, S.; Davis, P.; Chau, A.; Galgano, S.J.; Chapin, B.F.; Schuster, D.M.; Turnbull, C.M. Detection Rates of PSMA-PET Radiopharmaceuticals in Recurrent Prostate Cancer: A Systematic Review. Diagnostics 2025, 15, 1224. https://doi.org/10.3390/diagnostics15101224

AMA Style

Rais-Bahrami S, Davis P, Chau A, Galgano SJ, Chapin BF, Schuster DM, Turnbull CM. Detection Rates of PSMA-PET Radiopharmaceuticals in Recurrent Prostate Cancer: A Systematic Review. Diagnostics. 2025; 15(10):1224. https://doi.org/10.3390/diagnostics15101224

Chicago/Turabian Style

Rais-Bahrami, Soroush, Phillip Davis, Albert Chau, Samuel J. Galgano, Brian F. Chapin, David M. Schuster, and Catriona M. Turnbull. 2025. "Detection Rates of PSMA-PET Radiopharmaceuticals in Recurrent Prostate Cancer: A Systematic Review" Diagnostics 15, no. 10: 1224. https://doi.org/10.3390/diagnostics15101224

APA Style

Rais-Bahrami, S., Davis, P., Chau, A., Galgano, S. J., Chapin, B. F., Schuster, D. M., & Turnbull, C. M. (2025). Detection Rates of PSMA-PET Radiopharmaceuticals in Recurrent Prostate Cancer: A Systematic Review. Diagnostics, 15(10), 1224. https://doi.org/10.3390/diagnostics15101224

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop