• prostate
• cancer
• pet/ct
• psma

Aim of the study
The primary study objective was to assess the changes induced by the use of [68Ga]PSMA PET/CT in staging and in treatment decision making of patients with biochemical failure PCa.
The secondary objectives are:
1. to compare the diagnostic performances of [68Ga]PSMA PET/CT (ARM B) to the standard approach of [18F]FMCH PET/CT (ARM A) at different PSA levels
2. to define the contribution to risk stratification, resulting in a proper adaptive personalized treatment of patients with PCa after [68Ga]PSMA PET/CT and [18F]FMCH PET/CT
3. to identify new imaging biomarkers to advance the understanding of oligometastatic cancer by Radiomics Advanced analysis (Radiomics) of the [68Ga]PSMA PET/CT and [18F]FMCH PET/CT images in patients with oligometastatic (up to 3 active synchronous metastasis) and plurimetastatic disease (more than 3 synchronous metastasis)
4. to compare in the subgroup of patients who performed both [68Ga]PSMA-11 and [18F]FMCH scans, the contribution of each exam on the intention to treat, thus on patients’ management.
Methods
We enrolled 93 patients with BRPCa aged between 53 and 87 years. Two patients voluntarily interrupted the trial; therefore, we assessed 91 patients.
The inclusion criteria were:
- histologically documented PCa treated with radical prostatectomy or loco-regional EBRT
- BRPCa demonstrated by two consecutive PSA determinations
- ongoing hormonal therapy (HT) at the time of PET/CT scans
- male patients aged >18 years without upper age limit
- ability to understand and willingness to sign a written informed consent document
- written informed consent obtained according to international guidelines and local laws
The exclusion criteria were:
- other malignancies

Results
Between May 2021 and June 2022, we enrolled in the study 93 patients (mean age 74,1 years ± 7,6 years, median 76 years, range 53-87 years) with BRPCa after either primary RP (n=66) or EBRT (n=25) with radical intent. 40 patients were placed in the ARM A [18F]FMCH PET/CT (mean age 76,2 years ± 7,4 years, median 77 years, range 53-86 years) and 38 to ARM B [68Ga]PSMA-11 PET/ CT (mean age 71 years ± 6,6 years, median 72,5 years, range 58-82 years). Two patients voluntarily interrupted the trial; therefore, we assessed 91 patients. Most of the patients (n=22) presented a GS 8 (4+4), followed by 18 patients with GS 7 (4+3), 17 patients with 9 (4+5) and 15 patients with 7 (3+4). In 31 patients PSA undetectability was never reached. In the remaining ones, the mean time to biochemical recurrence was 54 months (median time of 36 months, range 4-228 months). The mean PSA value at the time of PET/CT was 30,6 ng/ml ± 135,1 (median 2,11 ng/ml, range 0,01-964 ng/ml).
A subgroup of these patients (n=13, mean age 73,5 years ± 6,4 years, median 74 years, range 62-87 years) performed both [18F]FMCH PET/CT and [68Ga]PSMA-11. In this subgroup the more represented Gleason Score was 8 (4+4, present in 33,3% of the population), followed by 7 (3+4, present in 16,7%). Patients were treated with RP in 11 cases (followed by EBRT in 2 patients) and with curative EBRT in 2 cases. The mean time to biochemical recurrence was 50,6 months (median time of 36 months ranging from 0 to 108 months) and the mean PSA value at the time of PET/CT was 1,81 ng/ml ± 1,73 (range 0,27 – 5,6 ng/ml). The mean PSA DT was 11,2 months ± 26,2 (range 0,0 – 70,6 months), the mean PSA velocity was 0,03 ng/ml/months ± 0,04 (range 0,0 – 0,11 ng/ml/months). At the time of PET/CT 13 patients were in ADT.
The statistical analysis demonstrated that there was a significant correlation between higher PSA values and bone and prostatic lodge localization.
With the radiomic signatures we showed that [68Ga]PSMA-11 can differentiate better than [18F]FMCH the oligometastatic patients, especially when using the <5 lesions threshold.
Regarding [68Ga]PSMA-11, we also tried to assess what it has already been successfully evaluated for [18F]FMCH, that is the intra-lesion heterogeneity and similarity and the radiomic silhouette analysis, in order to understand how the lesions’ inner characteristics can influence the disease itself.
We also demonstrated how a more specific radiotracer like [68Ga]PSMA-11 (compared to [18F]FMCH) can guide the intention to treat forward a more local yet aggressive treatment with curative intent in BRPCa patients with low PSA levels.

Conclusions
This study showed how clinically relevant data can be predicted by radiomic features analysis; these data can be implemented by the evaluation of a larger number of patients and lesions, to develop new methods and parameters for customized patient management.