To analyze the impact of [18F]F-Choline PET/CT findings on therapeutic management compared to conventional imaging techniques in the high-risk prostate cancer (PC) staging.
Materials and methodsObservational, longitudinal and retrospective study including patients with high-risk PC who underwent a [18F]F-choline PET/CT after initial staging with conventional imaging techniques (bone scan and abdomen-pelvis CT) between January 2018 and December 2023. Findings were classified as limited disease (lymph node involvement in pelvis and/or axial skeleton) or extended disease (extrapelvic lymph node involvement, involvement of extra-axial skeleton and/or distant sites). Finally, the impact of the results on therapeutic management and on disease volume reclassification (CHAARTED criteria) was analyzed.
ResultsOne hundred and nineteen patients were included (mean age: 68.43 ± 9.33 years, diagnostic prostate-specific antigen 64.22 ± 159.40 ng/mL). [18F]F-choline PET/CT was positive in 71.4% of patients (50.4% with limited disease and 21.0% with extended disease) versus 21.2% detected by conventional techniques (P < .001). Based on PET findings, 18% of patients had high-volume disease compared to 5% based on conventional imaging (P = .002). [18F]F-choline PET/CT findings led to a change in therapeutic management in 54 patients (45.4%). Among them, 11 (9.2%) received radiotherapy to the pelvic lymph nodes, 14 patients (11.8%) hormone therapy, 23 patients (19.3%) were candidates for therapy with new antiandrogens, and 6 cases (5%) received systemic chemotherapy.
Conclusion[18F]F-choline PET/CT is superior to conventional imaging techniques in high-risk prostate cancer staging, detecting 18% of patients with high-volume disease and leading to a change in therapeutic management in 45% of cases.
Critical Relevance Statement[18F]F-choline PET/CT is superior to conventional imaging techniques in high-risk prostate cancer staging.
Analizar el impacto de los hallazgos de [18F]F-colina PET/TC en comparación con las técnicas de imagen convencionales (TC y gammagrafía ósea) en la estadificación y manejo terapéutico del cáncer de próstata (CP) de alto riesgo.
Materiales y métodosEstudio observacional, longitudinal y retrospectivo que incluyó pacientes con CP de alto riesgo a los que se realizaron PET/TC con [18F]F-colina tras la estadificación inicial mediante técnicas convencionales (gammagrafía ósea y TC abdominopélvica) entre enero de 2018 y diciembre de 2023. Los hallazgos se clasificaron como enfermedad limitada (afectación de ganglios pélvicos y/o esqueleto axial) o enfermedad extendida (ganglios extrapelvianos, esqueleto extra-axial y/o mestástasis a distancia). Se analizó el impacto de los resultados en la toma de decisiones terapéuticas y en la reclasificación del volumen tumoral según los criterios CHAARTED.
ResultadosSe incluyeron 119 pacientes (edad media 68,4 ± 9,3 años; PSA diagnóstico 64,2 ± 159,4 ng/mL). La PET/TC con [18F]F-colina fue positiva en el 71,4% de los pacientes (50,4% con enfermedad limitada y 21% con enfermedad extendida) frente al 21,2% detectado por técnicas convencionales (P < ,001). Según los hallazgos de la PET/TC, el 18% de los pacientes presentó enfermedad de alto volumen frente al 5% detectado por técnicas convencionales (P = ,002). Los resultados de la PET/TC condujeron a un cambio en el manejo terapéutico en el 45.4% de los pacientes, concretamente el 9,2% recibieron radioterapia sobre los ganglios pélvicos, 11,8% terapia hormonal, 19,3% terapia con nuevos antiandrógenos (ARPI) y 5% quimioterapia sistémica.
ConclusiónLa PET/TC con [18F]F-colina es superior a las técnicas de imagen convencionales en la estadificación del CP de alto riesgo, detectando pacientes con enfermedad de alto volumen y provocando un cambio en la estrategia terapéutica en casi la mitad de los casos.
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[18F]F-choline PET/CT has higher sensitivity and specificity than conventional imaging techniques for high-risk prostate cancer staging.
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[18F]F-choline PET/CT detects high-volume disease in up to one in five patients with high-risk prostate cancer.
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PET/CT with [18F]F-choline leads to a change in the therapeutic approach in 44.5% of patients with high-risk prostate cancer.
Prostate cancer (PC) is the most predominant neoplasm among men, accounting for one of the main causes of mortality in this group. In Spain, an annual incidence of 35,000 cases and 6,000 deaths is estimated, with a slightly higher incidence rate than breast cancer.1–3 Therapeutic decisions to treat the primary tumour are currently based on parameters such as the prostate-specific antigen (PSA) value, clinical stage and Gleason score.
Initial staging plays a crucial role in the management of PC, especially in intermediate- and high-risk patients, since it allows optimising treatment options with curative intent. Conventional imaging modalities (CI), such as computed tomography (CT), magnetic resonance imaging (MRI) and bone scan (BS), have significant limitations in the detection of bone and lymph node metastases of small-volume, while BS, although accessible and inexpensive, has low specificity and may generate false positives.4
In recent years, positron emission tomography/computed tomography (PET/CT) with radiopharmaceuticals such as [18F]F-choline and [18F]F PSMA (prostate-specific membrane antigen) have proven to be promising and effective tools for the detection of visceral and lymph node metastases. [18F]F PSMA PET/CT is known for its high sensitivity and specificity, being superior to [18F]F-choline PET/CT, although with limited availability in some settings.5
Recent studies have compared the effectiveness of [18F]F-choline PET/CT versus conventional techniques in the initial staging of high-risk PC. The results show a higher diagnostic yield of PET/CT, with a positive impact on modifying treatment decisions and reducing unnecessary treatments. However, ongoing challenges still remain, such as low sensitivity for micrometastases and the need for further studies to assess its cost-effectiveness.6
In this context, PET/CT, either with [18F]F-choline or [18F]F PSMA, has become a crucial tool for PC staging, although its role in initial staging remains a matter of discussion. The National Comprehensive Cancer Network (NCCN) has begun to recommend the use of [18F]F-choline or [18F]F PSMA PET/CT, as an alternative to conventional techniques for the assessment of bone and visceral metastases in patients with high-risk PC.7
The aim of our research was to evaluate the diagnostic capacity of [18F]F-choline PET/CT in the initial staging of high-risk PC in comparison with conventional imaging techniques and to assess changes in therapeutic approach resulting from its outcome. The secondary goals were to determine predictive factors for a positive [18F]F-choline PET/CT result and to assess the degree of concordance between PET/CT and CI.
Material and methodsStudy design and participantsRetrospective observational study, in which 119 patients were consecutively include from the Hospital Virgen de las Nieves in Granada (60 patients) and Hospital Virgen del Rocío in Seville (59 patients) from June 2018 to December 2023 who had undergone [18F]F-choline PET/CT in their initial staging.
Patients were eligible if they met the following criteria:
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Diagnosis of high-risk PC according to NCCN of 20197 meeting at least one of the following criteria:
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PSA > 20 ng/mL
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Gleason score > 7 o ISUP 4–5
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From CT2c
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Locally advanced PC
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Previous abdomino-pelvic CT and bone scan.
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Subjected or not to radical prostatectomy.
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With an accessible clinical follow-up.
Patients with other cancer in their medical history, with metastases confirmed by histopathological examination and patients who had already received hormonal therapy or previous radio/chemotherapy were excluded.
The study protocol was conducted in accordance with the Declaration of Helsinki and all participants provided consent before undergoing any study procedure.
Patient recruitment was performed by retrospective patient assessment, taking into account demographic information, medical history, blood test results and histopathological data from prostate biopsy. All data collection was performed using a database.
Study proceduresThe interval between imaging procedures was less than 2 months.
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Abdomen and Pelvis CT: CT imaging was performed after contrast injection. For lymph node staging, the short axis of all nodes was measured with a threshold value of 10 mm. For distant metastases, abnormalities in the skeleton, liver, lung or adrenal gland were considered.
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Bone scan (BS): Whole body images were obtained in anterior and posterior views 2–3 h after [99mTc]Tc-HDP injection. Findings were considered positive if there were solitary or multiple asymmetric areas of uptake unrelated to recent trauma or osteoarticular degenerative disease. Negative findings were defined as the absence of areas of increased uptake, outside the physiological distribution of the tracer.
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PET/CT: A PET/CT was performed from the vertex to the proximal femur, in 6–7 beds (2–3 min per position), 60 min after intravenous administration of 3 MBq/kg [18F]F-choline. Low-dose CT (non-contrast; 140 kV, 80–120 mA) was used for attenuation correction and anatomical localisation of lesions. PET/CT images were interpreted jointly by 2 nuclear medicine specialists.
A quantitative and qualitative visual analysis was performed, determining the number of lesions and their location, along with the assessment of maximum SUL, mean SUL and minimum SUL, as well as MTV.
Variables analysedData was collected on patient and tumour characteristics: age at diagnosis, PSA at diagnosis (ng/mL), Gleason score, International Society of Urological Pathology (ISUP) prognostic group grade, tumour location, extent and clinical stage (TNM).
The results of conventional imaging tests and [18F]F-choline PET/CT were classified into local, nodal or metastatic involvement and the latter into oligometastatic (defined as ≤4 bone lesions) and polymetastatic disease (defined as >4 bone lesions or visceral disease).
Extent and risk stratification was assessed according to CHAARTED (low/high volume) and LATITUDE (low/high risk) criteria based on conventional and PET/CT scans.
In addition, the initially proposed treatment and whether there was a change in the therapeutic indication after the PET/CT results were collected.
Reference standardGiven the retrospective nature of the study and the lack of histological confirmation in most patients, a real-world clinical approach was adopted. In this context, imaging findings were validated using a composite reference standard that included clinical assessment, PSA kinetics, follow-up imaging, and multidisciplinary consensus when available. True-positive results were defined by concordant clinical or biochemical evidence of disease, while true-negative results were defined by clinical stability or biochemical remission during follow-up. This pragmatic methodology reflects actual clinical practice in settings where histological verification is not always feasible.
Outcome measuresThe main goal was to evaluate the diagnostic performance of [18F]F-choline PET/CT by calculating the diagnostic validity of the scan, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy.
The clinical impact of the PET/CT scan on subsequent patient management was systematically evaluated. “Change in therapeutic management” was defined as any modification of the initial treatment plan based on PET/CT findings, including changes in treatment modality or therapeutic intent (curative vs. palliative). To assess this, five treatment categories were considered: radical prostatectomy, radiotherapy (RT), androgen deprivation therapy (ADT), new androgen receptor pathway inhibitors (ARPI), and systemic chemotherapy (QT). Management decisions were recorded both before and after PET/CT to identify and quantify any changes.
As secondary aims we analysed:
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The extent/staging and risk stratification according to CHAARTED (low/high volume) and LATITUDE (low/high risk) criteria based on CI and [18F]F-choline PET/CT8
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Disease volume and risk based on [18F]F-choline PET/CT results.
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Correlations found between [18F]F-choline PET/CT quantification values and different clinical and analytical variables.
Descriptive analysis of quantitative variables was performed including measures of trend (mean or median) and central dispersion (standard deviation, range), as well as absolute and relative frequencies for qualitative variables. The Chi-square test or Fisher's exact test was used to compare proportions of independent samples, and McNemar's test was used to compare proportions of related samples. Kappa analysis was included to determine the agreement between [18F]F-choline PET/CT and CI (values of k > 0.4, >0.6 and >0.8 indicate reasonable, good and excellent agreement, respectively). For comparison of quantitative data between the different groups the Student's t-test for paired data was used as a parametric test and the Wilcoxon test as a non-parametric test. For the comparison of quantitative data according to the [18F]F-choline PET/CT final result by location, the analysis of variance (ANOVA) or the Kruskal-Wallis test was used, depending on the distribution of the data, applying the Bonferroni correction for multiple comparisons.
Sensitivity, specificity, PPV and NPV were calculated for CI and [18F]F-choline PET/CT. Sensitivity and specificity were calculated using clinical and biochemical follow-up as the reference standard. Histological confirmation was included only when available. To assess the discriminant ability of PSA with respect to the [18F]F-choline PET/CT result, the area under the curve (AUC) was studied by estimating a 95% confidence interval and establishing the best cut-off point. Finally, uni/multivariate binary logistic regression was used to establish independent factors associated with [18F]F-choline PET/CT outcome. The analysis was performed using SPSS software (v.15.0; IBM-SPSS) establishing P < .05 as statistical significance.
ResultsStudy populationThe study included 119 patients, whose baseline characteristics are shown in Table 1.
Baseline characteristics of the study population.
| Variable | Global (n = 119) |
|---|---|
| Age (mean ± SD; years) | 68.43 ± 9.33 |
| PSA diagnosis (mean ± SD; ng/mL) | 64.23 ± 159.40 |
| Gleason n (%) | |
| <6 | 9 (14.7) |
| 7 | 45 (37.8) |
| 8 | 27 (22.7) |
| 9 | 37 (31.1) |
| Not available | 1 (0.8) |
| ISUP n (%) | |
| 1 | 3 (2.5) |
| 2 | 13 (10.9) |
| 3 | 32 (26.9) |
| 4 | 35 (29.4) |
| 5 | 36 (30.3) |
| Extracapsular infiltration, n (%) | |
| No | 50 (42.0) |
| Yes | 54 (45.4) |
| SVs infiltration, n (%) | |
| No | 101 (84.9) |
| Yes | 11 (9.2) |
| Extent of disease by BS, n (%) | |
| Negative | 95 (79.8) |
| Axial | 16 (13.4) |
| Extra-axial | 5 (4.2) |
| Axial and extra-axial | 3 (2.5) |
| Extent of disease by CT, n (%) | |
| Negative | 79 (66.4) |
| Pelvis and/or axial | 32 (26.9) |
| Extra-pelvic and/or extra-axial | 8 (6.7) |
| PSA trigger (mean ± SD; ng/mL) | 45.45 ± 59.49 |
| [18F]F-choline PET/CT, n (%) | |
| Negative | 34 (28.6) |
| Positive | 85 (71.4) |
| Extent of disease PET/CT, n (%) | |
| Negative | 34 (28.6) |
| Pelvis and/or axial | 60 (50.4) |
| Extra-pelvic and/or extra-axial | 25 (21.0) |
| CI time interval (CT and BS) (mean ± SD; days) | 20.73 ± 39.23 |
| CI time interval and [18F]F-choline PET/CT (mean ± SD; days) | 72.73 ± 72.72 |
SD: standard deviation; BS: bone scintigraphy; CI: conventional imaging tests; SVs: seminal vesicles.
**The number of patients (n) and percentages (relative frequency in %) refer to the total number of patients included in the analysis, excluding missing values.
Based on TNM classification, [18F]F-choline PET/CT detected extracapsular extension of the primary tumour (T3) in 40.7% of cases vs. 21.8% for CI, P < .001. Similarly, the diagnostic ability of [18F]F-choline PET/CT was significantly higher than CI for detecting nodal (63.2% vs. 35.9%, P < .001) or distant (34% vs. 25%, P < .001). See Table 2.
Results of the staging and risk stratification study according to CHAARTED (low/high volume) and LATITUDE (low/high risk) criteria according to CI (CT and BS) and [18F]F-choline PET/CT.**
| Variable | Conventional imaging (CT + BS), n (%) | [18F]F-choline PET/CT, n (%) | P |
|---|---|---|---|
| T status, (n = 118) | < .001 | ||
| 1–2 | 86 (72.3) | 61 (51.7) | |
| 3 | 26 (21.8) | 48 (40.7) | |
| 4 | 6 (5) | 9 (7.6) | |
| N status, (n = 117) | < .001 | ||
| 0 | 75 (64.1) | 43 (36.8) | |
| 1 | 42 (35.9) | 74 (63.2) | |
| M status, (n = 118) | .014 | ||
| 0 | 89 (75.4) | 78 (66.1) | |
| 1a | 5 (4.2) | 18 (15.3) | |
| 1b | 21 (17.8) | 18 (15.3) | |
| 1c | 3 (2.5) | 4 (3.4) | |
| Extent of disease (n = 119) | < .001 | ||
| Negative | 79 (66.4) | 34 (28.6) | |
| Pelvis and/or axial | 32 (26.9) | 60 (50.4) | |
| Extra-pelvic and/or extra-axial | 8 (6.7) | 25 (21.0) | |
| CHAARTED (n = 118) | .109 | ||
| Low | 113 (95.8) | 107 (90.7) | |
| High | 5 (4.2) | 11 (9.3) | |
| LATITUDE (n = 118) | .146 | ||
| Low | 113 (95.8) | 107 (90.8) | |
| High | 5 (4.2) | 11 (9.2) |
BS: bone scan.
The diagnostic ability to detect metastatic disease (including nodal and bone involvement) of [18F]F-choline PET/CT showed an sensitivity of 95%, specificity of 95%, PPV of 99% and NPV of 76%, while for CI the sensitivity was 56%, specificity of 76%, PPV of 91% and NPV of 28%. There was a low correlation between the two diagnostic procedures, with 69 patients (60% of the total) matching, with a Kappa index of 0.175, P = .032.
Disease volume and risk (LATITUDE and CHAARTED criteria)Table 3 shows the results of the risk stratification of disease according CHAARTED and LATITUDE criteria on basis CI and [18F]F-choline PET/CT results, considering only true positive (TP) and true negative (TN) results. The [18F]F-choline PET/CT findings led to a statistically significant (P = .031) change in disease volume stratification (according to CHAARTED criteria) in 18 patients (16.8%) and risk stratification based on LATITUDE criteria in 11 patients (10.3%), although this change was not statistically significant (P = .146). There was a low correlation between the two techniques, with 81 (84%) of patients being classified in the same way, with a Kappa index of 0.224, P = .008.
Risk stratification according to CHAARTED (low/high volume) and LATITUDE (low/high risk) criteria based on conventional imaging (CT and BS) and [18F]F-choline PET/CT findings, excluding false negative and false positive results.
| Variable | Conventional imaging (CT + BS) | [18F]F-choline PET/CT | P |
|---|---|---|---|
| n (%) | n (%) | ||
| CHAARTED (n = 106) | |||
| Low | 101 (95.3) | 80 (83.3) | .031 |
| High | 5 (4.7) | 16 (16.7) | |
| LATITUDE (n = 106) | |||
| Low | 101 (95.3) | 95 (89.6) | .146 |
| High | 5 (4.7) | 11 (10.4) |
Among the [18F]F-choline PET/CT quantification parameters, MTV is the quantification parameter with the best high-volume discriminatory capacity (AUC 0.828, 95% CI 0.722–0.933), with the MTV value = 6.25 cm3 being the cut-off point that correctly discriminates 83% of the subjects with a sensitivity of 83.3% and a specificity of 76%. Fig. 1 shows the AUC determined by ROC curve analysis of the different quantification parameters of [18F]F-choline PET/CT. Fig. 2 also shows that the high volume group showed significantly higher mean MTV values (cm3) compared to the low volume group (53.06 ± 78.57 vs. 8.64 ± 21.36 respectively, P = .025).
![ROC curves showing the discriminatory ability of the different quantification parameters of [18F]F-choline PET/CT to CHARTEED high volume.](https://static.elsevier.es/multimedia/22538089/unassign/S2253808925001788/v1_202601150434/en/main.assets/gr1.jpeg?xkr=ue/ImdikoIMrsJoerZ+w997EogCnBdOOD93cPFbanNdV4B9vwZQjgKcZv3MP4CdsNwQlWjMJVGmnQkWYSILi5GNgjfQuFBtk30GrsghMxM/Eh/5LoYV8EROz2ueArcojCcd56VD36LK3aP9PyCA9bU36JFQPQ4+yOHWMTu0vQhpnShIB7jU/PB94ug1tP94RWqQLKZNxFsv/NN795XxQCvAZ7uTSDf/q6GFZXHc8tjI+Gan3lctD5imNgrJ2Ygd2P8ruAvhQ8LVue9RAfimhOxVG8/qG2LTPTYm/KO1R1Z3Lr2Ht2hu2Q2VO+tXLzIVwii6YW5qNr7EVy6mmCqNfkw==)
The initial therapeutic approach according to CI and [18F]F-choline PET/CT findings is shown in Table 4. [18F]F-choline PET/CT findings conditioned a modification in the initial treatment approach in 54 patients (45.4%, P < .001, Fig. 2). Of these patients, 9.2% (11/119) received radiotherapy (RT) to the pelvic lymph node chains, 11.8% (14/119 patients) received associated treatment with androgen deprivation therapy (ADT), 23/119 patients (19.3%) were candidates for therapy with the new androgen receptor pathway inhibitors (ARPI) and in 6/119 cases (5%) the extent of disease detected on [18F]F-choline PET/CT prompted treatment with Docetaxel (systemic chemotherapy), see Fig. 3. The level of concordance between the initially proposed treatment and the one performed after [18F]F-choline PET/CT was low (kappa index of 0.333, P < .01), resulting in changes in the therapeutic approach in 44.5% of the patients.
Therapeutic approach based on the findings of conventional imaging tests (CT + BS) and [18F]F-choline PET/CT.
| Variable | Conventional imaging tests (CT + BS) | [18F]F-choline PET/CT | P |
|---|---|---|---|
| n (%) | n (%) | ||
| Therapeutic approach, n (%) | < .001 | ||
| Radical | 51 (42.9) | 23 (19.3) | |
| RP/RT + ADT | 48 (40.3) | 58 (48.7) | |
| ADT + ARPI | 13 (10.9) | 27 (22.7) | |
| ADT + ARPI + Docetaxel | 7 (5.9) | 11 (9.2) |
RP: Radical Prostatectomy; RT: radiotherapy; ADT: androgen deprivation therapy; ARPI: androgen receptor pathway inhibitors.
![Sankey plot showing patient flow as a function of therapeutic approach according to conventional imaging (initial) and [18F]F-choline PET/CT findings (final).](https://static.elsevier.es/multimedia/22538089/unassign/S2253808925001788/v1_202601150434/en/main.assets/gr3.jpeg?xkr=ue/ImdikoIMrsJoerZ+w997EogCnBdOOD93cPFbanNdV4B9vwZQjgKcZv3MP4CdsNwQlWjMJVGmnQkWYSILi5GNgjfQuFBtk30GrsghMxM/Eh/5LoYV8EROz2ueArcojCcd56VD36LK3aP9PyCA9bU36JFQPQ4+yOHWMTu0vQhpnShIB7jU/PB94ug1tP94RWqQLKZNxFsv/NN795XxQCvAZ7uTSDf/q6GFZXHc8tjI+Gan3lctD5imNgrJ2Ygd2P8ruAvhQ8LVue9RAfimhOxVG8/qG2LTPTYm/KO1R1Z3Lr2Ht2hu2Q2VO+tXLzIVwii6YW5qNr7EVy6mmCqNfkw==)
The results of our study demonstrate that [¹⁸F]F-choline PET/CT is superior to conventional imaging (CI) in the initial staging of high-risk prostate cancer (PC), detecting a higher proportion of patients with nodal and distant involvement and, consequently, with a greater disease burden, which leads to a significant change in the initial therapeutic approach. Initial staging of high-risk PC remains challenging. Although the superiority of [¹⁸F]F-choline PET/CT over CI techniques (including CT and bone scintigraphy) is widely recognized, it is not recommended in most clinical practice guidelines.4,9
In our cohort, the overall sensitivity and specificity of CI were 56% and 76%, respectively, whereas [¹⁸F]F-choline PET/CT achieved 95% for both, clearly outperforming CI. Although variability exists depending on the type of analysis, radiotracer, and availability of histological confirmation, our results are consistent with previously published studies, such as Sopeña et al.,5 who reported 92.9% sensitivity and 83.3% specificity for [¹⁸F]F-choline PET/CT in 78 patients with high-risk PC, and Umbehr MH et al., who performed a meta-analysis including 637 patients, reporting 85% sensitivity and 79% specificity.6 Differences between our series and the literature may be explained by the fact that all patients in our study met high-risk criteria, implying a higher likelihood of extraprostatic involvement, and that many patients lacked histological confirmation, as this was an observational study reflecting routine clinical practice.
Regarding nodal involvement (N stage), [¹⁸F]F-choline PET/CT showed superior detection compared to CI (63.2% vs. 35.9%, P < .001). Similar results have been reported in recent studies, including a phase III trial by Evangelista et al.,10 which compared [¹⁸F]F-choline PET/CT (intervention) versus CI (control) for initial staging of high-risk PC, reporting nodal involvement detection rates of 77.8% versus 7.7%, respectively.
For distant metastases (M1 stage), [¹⁸F]F-choline PET/CT also outperformed CI, with detection rates of 34% versus 25% (P < .001). Other studies have reported comparable findings, with detection rates of approximately 29% for [¹⁸F]F-choline PET/CT and 27% for CI,10 though most literature focuses on bone involvement, where meta-analyses report pooled sensitivity and specificity of 79% and 82%, respectively.11
The concordance between [¹⁸F]F-choline PET/CT and CI in initial staging was low (Kappa: 0.175), with agreement in about one-third of patients, similar to Sopeña et al.5 (kappa = 0.134). Nevertheless, [¹⁸F]F-choline PET/CT is considered superior to CI and has proven more effective in detecting nodal disease and additional bone involvement.5,11
[¹⁸F]F-choline PET/CT findings led to a statistically significant (P = .031) change in disease volume stratification according to CHAARTED criteria in 18 patients (16.8%). To our knowledge, no prior studies have specifically evaluated the role of [¹⁸F]F-choline PET/CT in disease volume classification, likely due to the growing use of PSMA-based PET/CT tracers.12 Bodar et al.13 reported that PSMA PET/CT led to reclassification from low to high disease volume in 12.8% of patients with negative bone scans and 44.4% with positive scans, results comparable to our findings.
The impact of [¹⁸F]F-choline PET/CT on therapeutic decision-making was substantial and multifaceted. Here, a “change in therapeutic management” was defined to include any modification of the initially planned treatment, a shift in therapeutic intent (curative versus palliative), or initiation of therapy expected to confer clinical benefit. PET/CT findings led to management changes in 54 patients (44.5%, P < .001), approximately 50% of whom (23/54) were candidates for novel androgen receptor pathway inhibitors (ARPI), while others received targeted pelvic radiotherapy, combined androgen deprivation therapy (ADT), or systemic chemotherapy with Docetaxel. These results align with previously reported ranges for changes in intention-to-treat (5%–71%).14–16 The results support the importance of [18F]F-choline PET/CT in therapeutic decision making, not only in selecting patients who are candidates for hormone therapy, but also in selecting and planning external beam radiation therapy with radical intent.17
The low concordance between initially proposed and actual treatment post-PET/CT (kappa = 0.333, P < .01) underscores the significant impact of imaging on clinical decision-making. PET/CT not only revealed higher rates of extraprostatic disease and high-volume tumors compared to CI but also enabled clinicians to tailor therapeutic strategies accordingly. Patients with extensive nodal or metastatic disease were directed toward systemic or combined therapies, whereas those with localized disease received curative-intent interventions, including targeted radiotherapy with or without ADT.
These findings highlight the real-world utility of [¹⁸F]F-choline PET/CT as a tool for personalized, evidence-based treatment planning. By accurately delineating disease burden and identifying patients likely to benefit from specific therapies, PET/CT contributes to optimized management and improved alignment of treatment intent with disease characteristics.18 Our study confirms that [¹⁸F]F-choline PET/CT detects a greater proportion of patients with extraprostatic disease and high-volume metastases, leading to significant changes in initial management. Until PSMA-based radiotracers are universally available, [¹⁸F]F-choline PET/CT remains a pragmatic modality guiding treatment decisions and planning.
Currently, PSMA-PET/CT is the gold standard for staging high-risk prostate cancer19 Therefore, it is important to contextualize the results with respect to this technique and analyze the current role of F-choline in situations where PSMA is unavailable. Interest in [¹⁸F]F-choline PET/CT has declined due to the emergence of PSMA-based radiopharmaceuticals, now considered the most accurate for staging PC, particularly in high-risk cases where replacement of bone scintigraphy and abdominopelvic CT with PSMA PET/CT is suggested.4,9 Systematic reviews and meta-analyses comparing PSMA-based tracers and [¹⁸F]F-choline PET/CT have yielded conflicting results. Alberts et al.20 included 12 studies analyzing 13 radiotracers and concluded that although detection rates differ between PSMA and choline, there is insufficient evidence to favor any of the four routinely used PSMA ligands (PSMA-11, PSMA-1007, PSMA-I&T, DCFPyL) due to limited evidence and publication bias. Lin et al.21 observed no statistically significant difference between [⁶⁸Ga]Ga-PSMA PET/CT and [¹⁸F]F-choline PET/CT (sensitivity 92% vs. 93%, specificity 94% vs. 83%).
Several meta-analyses have confirmed that [¹⁸F]F-choline PET/CT achieves high diagnostic accuracy for nodal and distant metastases, enabling accurate disease burden assessment and aiding therapeutic planning.22 Head-to-head comparisons indicate that while PSMA tracers outperform F-choline at very low PSA levels, particularly in recurrent disease, their superiority is less pronounced at higher PSA levels and in first-line staging.20,23 Our findings confirm that [¹⁸F]F-choline PET/CT is effective in identifying distant metastases in high-risk PC, detecting up to 16% of patients with high-volume disease and leading to changes in treatment intent in a considerable number of cases. Understanding its performance in initial staging is essential for identifying scenarios where this test is most beneficial in daily practice.
The retrospective design and lack of histological confirmation in most patients represent inherent limitations. However, this real-world approach mirrors routine clinical decision-making, where management often relies on PSA dynamics, imaging findings, and multidisciplinary evaluation rather than systematic biopsy. This provides a pragmatic estimate of diagnostic performance in routine practice. Moreover, many previously published studies employ similar methodologies, using follow-up imaging and PSA as confirmation.5,10,16
ConclusionsIn our series, [¹⁸F]F-choline PET/CT outperformed conventional imaging in the initial staging of high-risk prostate cancer, detecting a higher proportion of patients with extraprostatic disease and high-volume metastases. Importantly, PET/CT findings led to modifications in the initial therapeutic approach in 45% of patients, highlighting its clinical relevance in treatment planning. Nevertheless, prospective studies are warranted to confirm these results and to evaluate the ongoing role of [¹⁸F]F-choline PET/CT in the era of PSMA-based radiopharmaceuticals.
CRediT authorship contribution statementThe authors confirm contribution to the paper as follows: study conception and design: EMTI, ARG, RMAP and JMFM, data collection: CCP, JLVP, LBS, analysis and interpretation of results: EMTI, ARG, RMAP, VPG, ICL, JMHG. JMFM, draft manuscript preparation: CCP, JLVP, LBS, EMTI, ARG, RMAP. All authors reviewed the results and approved the final version of the manuscript.
Informed consentWritten informed consent from patients was waived due to the retrospective nature of the research.
Ethical approvalThis retrospective study was conducted using anonymized clinical data. In accordance with national regulations and the European General Data Protection Regulation (GDPR, EU 2016/679), specific approval from the Institutional Review Board/Ethics Committee was not required. The obligation to obtain informed consent was waived, as the study involved no intervention and entailed minimal risk to participants. The research complied with the ethical principles of the Declaration of Helsinki and its subsequent amendments.
FundingNo funds, grants or other support was received.
The authors have no competing interests to declare that are relevant to the content of this article.
