Stesura Seveso Archivio Italiano di Urologia e Andrologia 2024; 96(1):12132 1 ORIGINAL PAPER of primary PCa tumours have low PSMA activity which evade detection by PSMA PET, mostly in high-grade and variant tumour types (7-10). Prostatic ductal adenocarcinoma (DAC) is an uncommon variant of prostatic carcinoma with aggressive behavior and worse prognosis and, still today, the of role PSMA PET/CT in its diagnosis and staging has not been clearly established (11). We evaluated the accuracy of fluoride 18 (18-F) PSMA PET/CT in the diagnosis and clinical staging in two patients with DAC. CASE REPORT Two Caucasian men 58 and 62 years old were admitted to our Department for dysuria: the patients had not famil- iarity for PCa and assumed antihypertensive drugs. PSA values were equal to 5.6 and 2.8 ng/ml, digital rectal examination was highly suspicious for PCa and magnetic resonance image (mpMRI) showed for both the presence of a index lesion Prostate Imaging Reporting and Data System (PIRADS) score 5. The patients underwent extend- ed transperineal prostate biopsy (18 cores) combined with four mpMRI/TRUS fusion biopsy using a 18 gauge needle under sedation and antibiotic prophylaxis (12, 13). The biopsy histology demonstrated the presence of a mixed PCa characterized by ductal and acinar PCa (Grade Group 4/Gleason score 8) with a Greatest Percentage of Cancer equal to 100%, a mean number of positive cores of 15 (3 targeted cores and 12 systematic biopsies)) and a mean total percentage of cancer equal to 45% (35-55%). The clinical staging performing lung and abdominal CT plus technetium-based bone scan did not demonstrate distant metastases and/or others primitive tumors; in addition, the 18-F PSMA PET/CT (5) showed in both patients an intraprostatic lesion provided of a standard- ized uptake value (SUVmax) equal to 4.6 and 4.9 in the absence of distant lesions suspicious for metastases (Figure 1). Following multidisciplinary evaluation, the patients underwent open radical prostatectomy (RP) plus extended pelvic lymphadenectomy. Definitive specimen showed the presence in both cases of a mixed pT3bN1 PCa (ductal plus acinar Grade Group 4/Gleason score 8) with positive surgical margins, perineuronal invasion and nodes metastases (5/20 and 6/24, respectively). Post- operative PSA (one month from surgery) in the two patients was 0.8 and 0.3 ng/ml, therefore patients under- Introduction: To evaluate the accuracy of PSMA PET/CT in the diagnosis and clinical staging of prostatic ductal adenocarcinoma (DAC). Materials and methods: Two Caucasian men 58 and 62 years old were admitted to our Department for dysuria: the patients had not familiarity for prostate cancer (PCa), PSA values were 5.6 and 2.8 ng/ml, digital rectal examination was positive, mul- tiparametric magnetic resonance image (mpMRI) showed for both the presence of an index lesion PIRADS score 5. The patients underwent extended transperineal prostate biopsy com- bined with four mpMRI/TRUS fusion biopsy under sedation and antibiotic prophylaxis; biopsy histology demonstrated the pres- ence of a mixed PCa characterized by DAC and acinar PCa (Grade Group 4/Gleason score 8). The patients underwent clini- cal staging performing lung and abdominal CT, bone scan and fluoride 18 (18F) PSMA PET/CT. Results: Conventional imaging was negative for distant metas- tases; 18F-PSMA PET/CT showed in both patients an intrapro- static lesion characterized by a standardized uptake value (SUVmax) equal to 4.6 and 4.9 in the absence of distant lesions suspicious for metastases. Following multidisciplinary evalua- tion, the patients underwent radical prostatectomy plus extend- ed pelvic lymphadenectomy. Definitive specimen showed the presence in both cases of a mixed pT3bN1 PCa (ductal plus aci- nar pattern Grade Group 4) with positive surgical margins, neu- ronal invasion, and nodes metastases (5/20 and 6/24, respective- ly). Post-operative PSA in the two patients was 0.8 and 0.3 ng/ml, therefore patients underwent adjuvant therapy. Conclusions: Conventional imaging and PSMA PET/CT could result inadequate in clinical staging of DAC, the use of more imaging data (i.e. mpMRI and/or F-18 FDG) could improve overall accuracy. KEY WORDS: PSMA PET/CT; Prostate cancer; Ductal PCa; Ductal PCa staging. Submitted 25 November 2023; Accepted 30 November 2023 INTRODUCTION Prostate cancer (PCa) is the most commonly diagnosed malignancy in men; although, conventional imaging with computed tomography (CT) and technetium-based bone scan are widely used for staging, recently, cumulative evi- dence indicates that prostate-specific membrane antigen (PSMA) positron-emission tomography (PET/CT) should be a centerpiece of diagnosis and staging for intermediate/high risk patients (1-5). Although, PSMA PET/CT seems about 27% more accurate than conventional imaging (6), 5-10% Ductal prostate cancer staging: Role of PSMA PET/CT Pietro Pepe 1, Ludovica Pepe 1, Mara Curduman 2, Michele Pennisi 1, Filippo Fraggetta 3 1 Urology Unit, Cannizzaro Hospital, Catania, Italy; 2 Pathology Unit, Cannizzaro Hospital, Catania, Italy; 3 Pathology Unit, Gravina and S. Pietro Hospital, Caltagirone (CT), Italy. DOI: 10.4081/aiua.2024.12132 Summary Archivio Italiano di Urologia e Andrologia 2024; 96(1):12132 P. Pepe, L. Pepe, M. Curduman, M. Pennisi, F. Fraggetta 2 went adjuvant radiotherapy of prostatic fossa and andro- gen deprivation therapy (ADT). DISCUSSION DAC is rare, aggressive, and characterized by cancer involving ducts and/or acini usually associated with a high-grade Gleason score/Grade Group, large tumor vol- ume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion (14, 15). In the WHO Classification fifth edition the term ‘duc- tal adenocarcinoma’ is now reserved for those radical prostatectomy cases with more than 50% ductal morphol- ogy, while in needle biopsy cases the term ‘adenocarcino- ma with ductal features’ is recommended for both pure ductal and mixed ductal and acinar features (16). Although DAC is treated with conventional therapies, it demonstrated worse outcomes in comparison with high- grade acinar PCa, regardless of the treatment modality. Ranasinghe et al. (17) in 228 men with DAC submitted to RP vs. radiotherapy demonstrated a 5-yrs overall survival (OS) and metastases free survival (MFS) equal to 75 vs. 62% and 88 vs. 82%, respectively; in addition, 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS and was characterized in 91% of them by intrinsic upregulation of androgen-resistant pathways. Although mpMRI and PSMA PET/CT are provided of superimposable accuracy in the diagnosis of high risk PCa (12, 18) showing direct correlation between PIRADS score and SUVmax values (19), in the presence of DAC only mpMRI (20) allows to perform diagnosis because PSMA PET/CT demonstrated a very limited diagnostic accuracy (21). In this respect, PSMA uptake has sometimes been poor compared with prominent 18-flourodeoxyglucose (F-18 FDG) avidity, which would suggest that FDG PET/CT scans are important in staging of ductal pattern (22, 23). The diagnostic utility of dual-tracer FDG/PSMA PET/CT for PCa may assist in characterizing high-risk dis- ease during primary staging and restaging especially with concurrently negative PSMA PET. When applied to high- risk or variant histology (i.e., DAC), detection of the FDG- positive phenotype may signal a poorer prognosis to prompt more aggressive intervention earlier in the disease course and dual PSMA/FDG PET/CT may improve onco- logical outcomes (24); in definitive, the use of PSMA and FDG PET imaging in PCa should be examined individual- ly and the potential diagnostic impact for individual patients to undergo dual-tracer PET imaging could be reserved in case of inconclusive conventional imaging and/or negative PSMA PET (25). In our series, both the patients had a negative conven- tional imaging (CT and technetium-based bone scan) and 18F PSMA PET/CT despite a locally advanced disease with the presence of metastatic nodes (pT3bN1) under- lining the lower accuracy of imaging in local and distant staging in case of DAC. 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Correspondence Pietro Pepe, MD (Corresponding Author) piepepe@hotmail.com Ludovica Pepe, MD ludopepe97@gmail.com Michele Pennisi, MD michepennisi2@virgilio.it Unità Operativa di Urologia, Azienda Ospedaliera Cannizzaro, Catania, Italy Mara Curduman, MD mara.curduman@aoec.it Unità Operativa di Anatomia Patologica, Azienda Ospedaliera Cannizzaro, Catania, Italy Filippo Fraggetta, MD filippofra@hotmail.com Unità Operativa Anatomia Patologica, Presidio Ospedaliero Gravina e San Pietro, Caltagirone, Italy Conflict of interest: The authors declare no potential conflict of interest.