Advances in radiology and pathology of prostate cancer: a review for the pathologist.

Multiparametric magnetic resonance imaging (mpMRI) has improved systematic prostate biopsy procedures in the diagnosis of clinically significant prostate cancer (csPCa) by reducing the number of unnecessary biopsies; numerous level one evidence studies have confirmed the accuracy of MRI-targeted biopsy, but, still today, systematic prostate biopsy is recommended to reduce the 15-20% false negative rate of mpMRI. New advanced imaging has been proposed to detect suspicious lesions and perform targeted biopsies especially when mpMRI cannot be performed. Transrectal ultrasound (TRUS) modalities are emerging as methods with greater sensitivity and specificity for the detection of PCa compared to the traditional TRUS; these techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach: multiparametric ultrasound (mpUS). More recently, micro-ultrasound (MicroUS) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) have demonstrated to be sensitive for the detection of primary prostatic lesions resulting highly correlated with the aggressiveness of the primary prostatic tumor. In parallel, artificial intelligence is advancing and is set out to deeply change both radiology and pathology. In this study we address the role, advantages and shortcomings of novel imaging techniques for Pca, and discuss future directions including the applications of artificial intelligence-based techniques to imaging as well as histology. The significance of these findings for the practicing pathologist is discussed.

A study of gene expression by RNA-seq in patients with prostate cancer and in patients with Parkinson disease: an example of inverse comorbidity.

BACKGROUND: Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with the presence of Lewy bodies and genetic factors are involved in its pathogenesis. Several studies have indicated that the expression of target genes in patients with PD is inversely related to cancer development; this phenomenon has been named "inverse comorbidity". The present study was undertaken to evaluate whether a genetic dysregulation occurs in opposite directions in patients with PD or PCa. METHODS AND RESULTS: In the present study, next-generation sequencing transcriptome analysis was used to assess whether a genetic dysregulation in opposite directions occurs in patients with PD or PCa. The genes SLC30A1, ADO, SRGAP2C, and TBC1D12 resulted up-regulated in patients with PD compared to healthy donors as controls and down-regulated in patients with PCa compared with the same control group. CONCLUSIONS: These results support the hypothesis of the presence of inverse comorbidity between PD and PCa.

Is it Time to Perform Only Magnetic Resonance Imaging Targeted Cores? Our Experience with 1,032 Men Who Underwent Prostate Biopsy.

PURPOSE: We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging to diagnose clinically significant prostate cancer and compared it with the diagnostic accuracy of transperineal saturation prostate biopsy. MATERIALS AND METHODS: From January 2011 to February 2018 repeat saturation prostate biopsy (the reference test) was done due to suspicion of cancer in 1,032 men with a median age of 63 years in whom median prostate specific antigen was 8.6 ng/ml. All patients underwent 3.0 Tesla pelvic multiparametric magnetic resonance imaging before saturation prostate biopsy. Additional targeted fusion prostate biopsy was done of lesions with a PI-RADS™ (Prostate Imaging Reporting and Data System) score of 3 or greater. RESULTS: T1c prostate cancer was found in 372 of the 1,032 patients (36%). Of these cases 272 (73.1%) were classified as clinically significant prostate cancer. Saturation prostate biopsy vs targeted fusion prostate biopsy and a PI-RADS score of 3 or greater vs targeted fusion prostate biopsy and a PI-RADS score of 4 or greater diagnosed 95.6% vs 83.8% vs 60.3% of clinically significant prostate cancers (p <0.0001). Saturation prostate biopsy missed 12 of 272 clinically significant prostate cancers (4.5%) vs 44 (16.2%) and 108 of 272 (39.7%) missed by targeted fusion prostate biopsy and a PI-RADS score of 3 or greater and a score of 4 or greater, respectively (p <0.0001). As a triage test multiparametric magnetic resonance imaging would have spared 49.3% vs 73.6% of patients using a PI-RADS cutoff of 3 or greater vs 4 or greater. CONCLUSIONS: Multiparametric magnetic resonance imaging could significantly reduce the number of unnecessary repeat prostate biopsies in about 50% of cases in which a PI-RADS score of 3 or greater is used. At the same time patients should be informed of the 16.2% and 39.7% false-negative rates of clinically significant prostate cancer for targeted fusion prostate biopsy of PI-RADS 3 or greater and 4 or greater lesions, respectively.

Can MRI/TRUS fusion targeted biopsy replace saturation prostate biopsy in the re-evaluation of men in active surveillance?

PURPOSE: The detection rate for significant prostate cancer of mMRI/TRUS fusion targeted biopsy versus saturation prostate biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol. METHODS: From May 2013 to January 2015, 40 men aged 66 years (median) with very low-risk PCa were enrolled in an AS protocol, and eligible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density <0.20, ≤2 unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core ≤50 %. All patients underwent 3.0-Tesla pelvic mpMRI before confirmatory transperineal saturation biopsy (SPBx; median 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (median 4 cores) of suspicious lesions (PI-RADS 4-5). RESULTS: Ten out of 40 (25 %) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI found all the lesions predictive of significant PCa showing a false-positive rate equal to 5 %; on the contrary, mpMRI/TRUS targeted biopsy missed 3/10 (30 %) significant PCa characterised by the presence of a single positive core of GS ≥ 7 and GPC ≤ 5 %, suggesting that reduced number of targeted biopsies could miss small but significant PCa. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value of mpMRI in diagnosing significant PCa were 95.2, 100, 93.8, 83.4, 100 %, respectively. CONCLUSIONS: Although mpMRI provided high diagnostic accuracy (about 95 %) in diagnosing clinically significant PCa, mpMRI/TRUS fusion targeted biopsy cannot replace SPBx at confirmatory biopsy of men enrolled in AS protocols.

Accuracy of pelvic multiparametric MRI in diagnosing local recurrence following radical prostatectomy. Case report and revision of the literature.

A Caucasian man (73 years old) six years from radical prostatectomy for prostate cancer (PCa) showed biochemical recurrence (BCR); the follow up based on PSA evaluated every 6 months was negative (0.1 ng/ml) for 5 years, but in the last year PSA increased to 0.3 vs 0.5 ng/ml. The patient was asymptomatic and underwent 3.0 Tesla mpMRI equipped with surface 16 channels phased-array coil placed around the pelvic area; multiplanar turbo spin-echo T2-weighted (T2W), axial diffusion weighted imaging (DWI), axial dynamic contrast enhanced (DCE) and spectroscopy were performed. Pelvic mpMRI demonstrated the presence of a nodular tissue with a diameter of 10 mm. located on the left of the prostatic fossa near the rectum that was higly sospicious for local PCa recurrence. The patient underwent salvage RT (64 Gy); one year from RT PSA was 0.1 ng/ml suggesting that the patient was free from recurrence. In conclusion, mpMRI could be combined with PSA kinetics in the evaluation of men with BRC also in the presence of PSA values < 1 ng/ml.

Azoospermic patient's treatment: An experience of a PMA hospital unit and role of ultrasonography.

INTRODUCTION: Azoospermia causes about 10% of male infertility and the best therapeutic option is the retrieval of sperm from testis or epididymis. MATERIAL AND METHODS: From Juanary 2008 to June 2016, 92 men (median 36 years; range: 25-54 years) were submitted in 47 cases to TESE (testicular sperm extraction) and in 45 cases to PESA (percutaneous epididymal sperm aspiration) for secretory and obstructive azoospermia, respectively; moreover, all the patients previously underwent color Doppler ultrasound of the testis and transrectal ultrasound of the prostate. RESULTS: Serum FSH values were 9.4 ml/UI and 36.4 ml/UI (median 18.2 ml/UI) with an estimated volume of the testis equal to 5 ml; 40 men had the mutation for cystic fibrosis with bilateral agenesis of the deferentia vasa, 4 men had a cyst of the prostatic utricle, 1 man had retrograde ejaculation, 7 had an epididymis cyst and 2 had anejaculation secondary to traumatic neurologic spinal cord injury. The retrieval of sperm was performed in 39 (83%) and 36 (80%) of the patients submitted to TESE and PESA, respectively. The pregnancy rate was equal to 28% and 33% in men with secretory and obstructive azoospermia, respectively. DISCUSSION: Assisted reproduction technology with a multidisciplinary team is provided of a pregnancy rate equal about 30% in men with azoospermia; ultrasound allows to evaluate abnormalities of the testis and prostate improving the percentage of pregnancy.

Detection rate for significant cancer at confirmatory biopsy in men enrolled in Active Surveillance protocol: 20 cores vs 30 cores vs MRI/TRUS fusion prostate biopsy.

INTRODUCTION: The detection rate for significant prostate cancer of extended vs saturation vs mMRI/TRUS fusion biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol. Mterials and methods: From May 2013 to September 2016 75 men aged 66 years (median) with very low risk PCa were enrolled in an AS protocol and elegible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density < 0.20, 2 < unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core < 50%. All patients underwent 3.0 Tesla pelvic mpMRI before confirmatory transperineal extended (20 cores) or saturation biopsy (SPBx; 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (4 cores) of suspicious lesions (PI-RADS 3-5). RESULTS: 21/75 (28%) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI lesions PI-RADS 4-5 vs PI-RADS 3-5 diagnosed 9/21 (42.8%) vs 16/21 (76.2%) significant PCa with 2 false positives (6.5%). The detection rate for significant PCa was equal to 76.2% (mpMRI/TRUS fusion biopsy) vs 81% (extended) vs 100% (SPBx) (p = 0.001); mpMRI/TRUS targeted biopsy and extended biopsy missed 5/21 (23.8%) and 4/21 (19%) significant PCa which were found by SPBx (p = 0.001) being characterised by the presence of a single positive core of GS ≥ 7 with GPC < 10%. CONCLUSIONS: Although mpMRI improve the diagnosis of clinically significant PCa, SPBx is provided of the best detection rate for PCa in men enrolled in AS protocols who underwent confirmatory biopsy.

Anterior prostate biopsy at initial and repeat evaluation: is it useful to detect significant prostate cancer?

PURPOSE: Detection rate for anterior prostate cancer (PCa) in men who underwent initial and repeat biopsy has been prospectively evaluated. MATERIALS AND METHODS: From January 2013 to March 2014, 400 patients all of Caucasian origin (median age 63.5 years) underwent initial (285 cases) and repeat (115 cases) prostate biopsy; all the men had negative digital rectal examination and the indications to biopsy were: PSA values > 10 ng/mL, PSA between 4.1-10 or 2.6-4 ng/mL with free/total PSA≤ 25% and ≤ 20%, respectively. A median of 22 (initial biopsy) and 31 cores (repeat biopsy) were transperineally performed including 4 cores of the anterior zone (AZ) and 4 cores of the AZ plus 2 cores of the transition zone (TZ), respectively. RESULTS: Median PSA was 7.9 ng/mL; overall, a PCa was found in 180 (45%) patients: in 135 (47.4%) and 45 (36%) of the men who underwent initial and repeat biopsy, respectively. An exclusive PCa of the anterior zone was found in the 8.9 (initial biopsy) vs 13.3% (repeat biopsy) of the men: a single microfocus of cancer was found in the 61.2% of the cases; moreover, in 7 out 18 AZ PCa the biopsy histology was predictive of significant cancer in 2 (28.5%) and 5 (71.5%) men who underwent initial and repeat biopsy, respectively. CONCLUSIONS: However AZ biopsies increased detection rate for PCa (10% of the cases), the majority of AZ PCa with histological findings predictive of clinically significant cancer were found at repeat biopsy (about 70% of the cases).

Ischemia of the glans penis following circumcision: case report and revision of the literature.

Ischemic complications of the glans penis are rare and commonly result from trauma, inadvertent administration of vasoconstrictive solutions, diabetes mellitus, circumcision and vasculitis; we refer about a young man with severe ischemia of the glans penis following circumcision. The patient had undergone circumcision 5 days before in a surgery department under local anesthesia (1% mepivacaine hydrochloride). The patient noticed a brownish color and edema of the glans penis at 24 h after he opened the wound dressing, but arrived to our hospital only 5 days after circumcision because these findings had progressed. Physical examination revealed the black color or necrotic appearance of the glans penis, and edema on the dorsal penile skin. The patient underwent antibiotic, antiplatatelet, corticosteroid and iperbaric therapy achieving a complete restitutio ad integrum.

Gleason score stratification according to age at diagnosis in 1028 men.

AIM OF THE STUDY: Gleason score stratification according to age at diagnosis has been retrospectively evaluated in 1028 men with biopsy-proven prostate cancer (PCa). MATERIAL AND METHODS: From January 2006 to December 2014, 2435 Caucasian men aged between 37 and 92 years underwent transperineal prostate biopsy for suspicion of PCa. The indications were as follows: abnormal digital rectal examination (DRE), PSA values > 10 ng/ml or between 4.1-10 or 2.6-4 ng/ml, with free/total PSA < 25% and < 20%, respectively. RESULTS: In 1028 (42.2%) patients with median PSA of 9.6 ng/ml a PCa was found (median age 62.3 years; range: 42-92 years); 757 (73.7%) vs. 271 (26.3%) men had a T1c vs. T2 clinical stage, respectively. Median Gleason score was 7 (range: 6-10). The Gleason score progressively increased with the age of the patients at diagnosis, and a significantly correlation between Gleason score ≥ 8 and men older than 80 years was demonstrated (p = 0.0001). CONCLUSIONS: The detection rate of aggressiveness of PCa progressively increased with the age at diagnosis; Gleason score ≥ 8 was more frequently diagnosed in men older than 80 years with PSA values > 10 ng/ml (about 80% of the cases) and abnormal DRE (about 60% of the cases).

Prostate biopsy: results and advantages of the transperineal approach--twenty-year experience of a single center.

PURPOSE: Detection rate for prostate cancer (PCa) and complications following transperineal prostate biopsy (TPBx) were reported. METHODS: From January 1991 to December 2012, 4,000 men underwent TPBx; from 1991 to 2001, the patients underwent biopsy for suspicious DRE or PSA values >4 ng/mL; moreover, from 2002, the indications were abnormal DRE, PSA >10 ng/mL, PSA values between 4.1 and 10, 2.6 and 4 and <2.5 ng/mL with F/T PSA <25, <20 <15 %, respectively. In case of initial biopsy, the number of needles cores increased from 6 (1991-1996) to 12 (1997-2012) and 18 cores (2002-2012); in case of repeat biopsy, since 2005 a saturation biopsy (SPBx) with >24 cores was performed. RESULTS: Overall, PCa, normal parenchyma, HGPIN and ASAP were found in 1,379 (34.5 %), 2,400 (60 %), 175 (4.4 %) and 46 (1.1 %) patients, respectively; in case of initial TPBx, the scheme at 18 showed a greater PCa detection in comparison with scheme at 6-12 cores (p < 0.05). In case of repeat biopsy, a higher detection of microfocus of cancer was found performing a SPBx; moreover, 15 % of cancers were localized in the anterior zone. Incidence of hemospermia and urinary retention were correlated with the number of needle cores resulting equal to 30.4 versus 11.1 % in case of SPBx (p < 0.05); moreover, none developed sepsis. CONCLUSIONS: Transperineal prostate biopsy (TPBx) resets the risk of sepsis; moreover, in case of repeat SPBx, the transperineal approach detects a high number of significant PCa localized in the anterior zone (15 % of the cases).

Detection rate of anterior prostate cancer in 226 patients submitted to initial and repeat transperineal biopsy.

OBJECTIVE: To evaluate the detection rate of anterior zone (AZ) prostate cancer (PCa) in patients submitted to initial and repeat transperineal prostate biopsy. METHODS: From January 2013 to August 2013, 226 patients (median age 64 years) with negative digital rectal examination underwent initial (144 cases) and repeat (82 cases) transperineal prostate biopsy for PSA >10 ng/ml, PSA 4.1-10.0 or 2.6-4.0 ng/ml with free/total PSA ≤25% and ≤20%, respectively. A median of 22 versus 32 cores were performed, including 4 cores of the AZ versus 6 cores (4 anterior plus 2 cores of the transition zone, TZ) at initial versus repeat biopsy, respectively. The detection rate of PCa of the peripheral zone (PZ), AZ and TZ was prospectively evaluated. RESULTS: The median PSA was 7.6 ng/ml; overall, a stage cT1c PCa was found in 104/226 (46%) patients, in 70 (48.6%) and 34 (41.5%) of the men who underwent initial and repeat biopsy, respectively. An AZ PCa was found in 11.5 vs. 8.8% (p = 0.32) of the patients submitted to initial versus repeat biopsy, respectively. AZ cancers demonstrated a number of positive cores (p = 0.03), greatest percentage of cancer (p = 0.001) and total percentage of cancer (p = 0.001) significantly lower in comparison with PZ PCa; moreover, 56.2 vs. 36.5% of AZ versus PZ PCa were characterized by a microfocus of cancer (p = 0.001), respectively. CONCLUSIONS: AZ biopsies increase the detection rate of PCa (about 10% of cases) at initial and repeat biopsy, allowing reduction of the biopsy false-negative rate.

Accuracy of 3 Tesla pelvic phased-array multiparametric MRI in diagnosing prostate cancer at repeat biopsy.

INTRODUCTION: Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated. MATERIALS AND METHODS: From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA >10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA < 25% and < 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. RESULTS: A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p < 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively. CONCLUSION: Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers.

Negative biopsy histology in men with PI-RADS score 5: is it useful PSMA PET/CT evaluation?

INTRODUCTION: To evaluate the accuracy of PSMA PET/CT in men with mpMRI PI-RADS score 5 negative biopsy histology. MATERIALS AND METHODS: From January 2011 to January 2023, 180 men with PI-RADS score 5 underwent systematic plus mpMRI/TRUS biopsy; 25/180 (13.9%) patients had absence of cancer and six months from biopsy were submitted to: digital rectal examination, PSA and PSA density exams, mpMRI and 68GaPSMA PET/CT evaluation (standardized uptake value "SUVmax" was reported). RESULTS: In 24/25 (96%) patients PSA and PSA density significantly decreased, moreover, the PI-RADS score was downgraded resulting < 3; in addition, median SUVmax was 7.5. Only 1/25 (4%) man had an increased PSA value (from 10.5 to 31 ng/ml) with a confirmed PI-RADS score 5, SUVmax of 32 and repeated prostate biopsy demonstrating a Gleason score 9/ISUP Grade Group 5 PCa. CONCLUSIONS: The strict follow up of men with PI-RADS score 5 and negative histology reduce the risk of missing csPCa especially if PSMA PET/CT evaluation is in agreement with downgrading of mpMRI (PI-RADS score < 3).

Oncological Outcomes in Men With Favorable Intermediate Risk Prostate Cancer Enrolled in Active Surveillance.

BACKGROUND/AIM: To evaluate the long-term oncological outcomes in men with intermediate risk prostate cancer (PCa) enrolled in active surveillance (AS). PATIENTS AND METHODS: From April 2015 to December 2022, 30 men with Gleason score 3+4/ISUP Grade Group2 (GG2), greatest percentage of cancer (GPC) ≤50%, Gleason pattern 4 ≤10%, ≤3 positive biopsy cores were enrolled in AS. All patients underwent confirmatory transperineal saturation biopsy (SPBx: 20 cores) 12 months from diagnosis plus multiparametric magnetic resonance (mpMRI) evaluation. At the last follow-up, 68Ga prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) was added: lesions with PIRADS score ≥3 and/or standardized uptake value (SUVmax) >5 were submitted to four targeted cores. RESULTS: Three out of 30 (10%) men with GG2 PCa were reclassified at confirmatory biopsy. At the last follow-up (median 5.2 years), only 2 of 27 (7.4%) men were reclassified and 23/30 (76.6%) continued AS. CONCLUSION: Men with favorable GG2 PCa enrolled in AS have good long-term oncological results. The use of selective criteria (i.e., SPBx, mpMRI, PSMA PET/CT) reduces the risk of reclassification.

Ductal prostate cancer staging: Role of PSMA PET/CT.

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, multiparametric magnetic resonance image (mpMRI) showed for both the presence of an index lesion PIRADS score 5. The patients underwent extended transperineal prostate biopsy combined with four mpMRI/TRUS fusion biopsy under sedation and antibiotic prophylaxis; biopsy histology demonstrated the presence of a mixed PCa characterized by DAC and acinar PCa (Grade Group 4/Gleason score 8). The patients underwent clinical staging performing lung and abdominal CT, bone scan and fluoride 18 (18F) PSMA PET/CT. RESULTS: Conventional imaging was negative for distant metastases; 18F-PSMA PET/CT showed in both patients an intraprostatic 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 evaluation, the patients underwent radical prostatectomy plus extended pelvic lymphadenectomy. Definitive specimen showed the presence in both cases of a mixed pT3bN1 PCa (ductal plus acinar pattern Grade Group 4) with positive surgical margins, neuronal invasion, and nodes metastases (5/20 and 6/24, respectively). 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.

PSMA PET/CT Accuracy in Diagnosing Prostate Cancer Nodes Metastases.

BACKGROUND/AIM: This study aimed to evaluate the diagnostic accuracy of prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) in pelvic nodal staging, using postoperative histopathology data as the reference standard. PATIENTS AND METHODS: From January 2020 to June 2024, 78 patients with clinically significant prostate cancer (PCa) (ISUP Grade Group 2) underwent radical prostatectomy plus extended pelvic lymph node dissection (ePLND): 60 (77%) vs. 18 (23%) men had an intermediate vs. high risk PCa. All the patients underwent PSMA PET/TC before surgery for clinical staging and nodes focal uptake (standardized uptake value "SUVmax) was evaluated to rule out the presence of metastases. RESULTS: PSMA PET/CT was suspicious for nodes metastases in 16/78 (20.5%) men (median SUVmax 26.2), conversely, histology demonstrated nodes metastases in 18/78 (23.1%). PSMA PET/CT was negative for nodal involvement in all Grade Group 2 (GG2) PCa, positive in 4/4 (100%) GG3 PCa, and in 10/14 (71.4%) GG5 PCa. In detail, PSMA PET/CT was false negative in 2/4 PCa, characterized by GG5 plus ductal adenocarcinoma. Overall, PSMA PET/CT sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy in diagnosing nodal metastases were equal to 87.5, 96.8, 87.5 96.7, and 92.3%, respectively. CONCLUSION: PSMA PET/CT demonstrated an overall diagnostic accuracy of 92.3% in nodal staging (100% in GG2 PCa), which decreased to 63.6% in GG5 PCa. In high-risk patients or in case of ductal adenocarcinoma, a negative PSMA PET/CT does not rule out the need for ePLND.

Salvage Radiotherapy PSMA PET/CT-guided in Men With PSA Recurrence.

BACKGROUND/AIM: To evaluate the clinical outcome in men with recurrent prostate cancer (PCa) treated by salvage radiotherapy (sRT) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT)-guided. PATIENTS AND METHODS: From January 2021 to January 2023, 33 patients who previously underwent definitive/systemic therapy were submitted to sRT PSMA PET/CT-guided for PCa recurrence: 16 (48.5%) on the prostate bed (PB), 12 (36.4%) on the lymph node (LN) and five (15.1%) on the bone. The median PSA value was 3.3 ng/ml (range=0.3-15.5 ng/ml): 0.2-0.5 ng/ml (18.2% cases), 0.51-1 ng/ml (39.4% cases) and >1 ng/ml (42.4% cases). Median 18F PSMA PET/CT standardized uptake value (SUVmax) was evaluated on PB, vs. LN vs. bones PCa recurrences and was equal to 12.5 vs. 19.0 vs. 30.1, respectively. RESULTS: Overall, at a median follow up of 12 months, 23/33 patients (69.7%) had local control without distant progression (PSA and SUVmax evaluation): 14/16 (87.5%) vs. 7/12 (58.3%) vs. 2/5 (40%) underwent sRT on the PB vs. LN vs. bone metastases, respectively. CONCLUSION: PSMA PET/CT allows to perform sRT early in men with PCa recurrence and low PSA values obtaining a complete clinical response in approximately 70% of the cases one year from treatment.

Transcriptome Analysis in Patients With Muscle-invasive Bladder Cancer.

BACKGROUND/AIM: Bladder cancer (BC) is the most prevalent malignant tumor in the urinary tract, classified mainly into muscle-invasive BC (MIBC) and non-MIBC (NMIBC). Recent studies highlight the important role of changes in transcriptome activity in carcinogenesis, aiding in the identification of additional differentially regulated candidate genes, improving our understanding of the molecular basis of gene regulation in BC. This study aimed to evaluate the transcriptome of MIBC patients compared with normal subjects. MATERIALS AND METHODS: mRNA sequencing was conducted using the Illumina NovaSeq 6000 Dx system in a case series comprising 11 subjects with MIBC and 19 healthy controls matched for age and sex. For functional analysis, the pathfindR package was utilized to comprehensively identify pathways enriched in omics data within active subnetworks. RESULTS: Our results demonstrated the presence of differentiated pathways, including spliceosome activity, oxidative phosphorylation, and chemical carcinogenesis due to reactive oxygen species, in MIBC patients compared with controls. CONCLUSION: The identification of novel molecular pathways in MIBC patients could prove useful in defining cancer predisposition factors and exploring potential therapeutic options.

Prostate cancer detection rate at repeat saturation biopsy: PCPT risk calculator versus PCA3 score versus case-finding protocol.

INTRODUCTION: To evaluate Prostate Cancer Prevention Trial (PCPT) risk calculator versus prostate cancer gene 3 (PCA3) score versus case-finding protocol accuracy in prostate cancer diagnosis in patients with prostate-specific antigen (PSA) below 10 ng/mL submitted to repeat saturation biopsy (SPBx). MATERIALS AND METHODS: From December 2010 to December 2011, 100 patients (median 66 years) underwent a SPBx (median 30 cores); the indications for repeat biopsy were those of a case-finding protocol: PSA values between 4.1 ng/mL-10 ng/mL or 2.6 ng/mL-4 ng/mL with F/T PSA ≤ 25% and ≤ 20%, respectively. All patients had negative digital rectal examination (DRE) and median PSA was 7.9 ng/mL. The performance of PCPT risk calculator (alone, combined with PSA free/total ( F/T) or PCA3 score) and PCA3 score in comparison with the case-finding protocol results (alone or combined with PCA3 score) was retrospectively evaluated in terms of detection rate for cancer and number of avoided biopsies. RESULTS: Prostate cancer was found in 28 (28%) patients; in the presence and absence of prostate cancer median PCA3 score was 57 versus 35 (p < 0.05). Using PCPT risk calculator (cut off probability of 25%) combined with PCA3 score no prostate cancer would be missed avoiding 8% of unnecessary biopsies. PCA3 score > 20 missed 7.2% of cancer; the case-finding protocol combined with PCA3 score > 35 would save 22% of avoidable biopsies, missing no cancer if all patients with PSA F/T ≤ 15% would undergo prostate biopsy irrespective of PCA3 values. CONCLUSIONS: PCA3 score improves PCPT risk calculator accuracy in prostate cancer diagnosis; moreover, PCA3 score combined with PSA F/T reduce number of unnecessary biopsies (about 20%).