The Radiolabeling of [161Tb]-PSMA-617 by a Novel Radiolabeling Method and Preclinical Evaluation by In Vitro/In Vivo Methods.

Background: Prostate cancer (PC) is the most common type of cancer in elderly men, with a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently, [161Tb], a radiolanthanide introduced for treating micrometastatic foci, has shown great promise for treating prostate cancer. Results: In this study, Terbium-161 [161Tb]Tb was radiolabeled with prostate-specific membrane antigen (PSMA)-617 ([161Tb]-PSMA-617) and the therapeutic efficacy of the radiolabeled compound investigated in vitro and in vivo. [161Tb]-PSMA-617 was found to have a radiochemical yield of 97.99 ± 2.01% and was hydrophilic. [161Tb]-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 hours. In vitro, [161Tb]-PSMA-617 showed a cytotoxic effect on LNCaP cells but not on PC-3 cells. In vivo, scintigraphy imaging visualized the accumulation of [161Tb]-PSMA-617 in the prostate, kidneys, and bladder. Conclusions: The results suggest that [161Tb]-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer.

Should Targeted Biopsy be Performed in Patients Who Have Only Pi-rads 3 Lesions?

OBJECTIVE: To determine whether clinical or radiological parameters can predict clinically significant prostate cancer (csPC) in patients with the Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions. PATIENTS AND METHODS: Data were obtained from 247 patients with PI-RADS 3 lesions on mpMRI and who had received a software guided transperineal/transrectal MRI/transrectal ultrasonography (MRI/TRUS) fusion prostate biopsy with concomitant standard systematic 12-core biopsy following mpMRI in the prostate cancer and prostate biopsy database of Turkish Urooncology Association, between 2016 and 2020. The cut-off values of clinical parameters were determined using receiver operating characteristic (ROC) curve analysis. Simple and multiple logistic regression analyses were performed to determine the clinical parameters in predicting csPC. RESULTS: A total of 56 patients (22.6%) had prostate cancer, 23 (9.3%) of whom had csPC. In the lesion- based analysis, cancer detection rates (CDRs) of each lesion in targeted biopsy were found to be 6% and 5% for ISUP GG 1 and ISUP GG ≥ 2, respectively. In the patient-based analysis, clinically insignificant CDRs were significantly higher in systematic biopsy compared with targeted biopsy, whereas no significant difference was found in terms of clinically significant CDRs (p = 0.020 and p=0.422, respectively). The cut-off values were determined as 48.3 mL (AUC [95% CI] = 0.68 [0.53-0.82]) for prostate volume, and 0.213 ng/mL/mL (AUC [95% CI] = 0.64 (0.51-0.77]) for PSAD in predicting csPC. In the multiple logistic regression analysis, only PSAD was found to be an independent risk factor in predicting csPC (OR [95% CI]: 3.56 [1.15-10.91], p = 0.024). CONCLUSION: Since PSAD > 0.20 ng/mL/mL was found to be positive independent risk factor in predicting csPC, in the absence of advanced radiological parameters, PSAD could be used for the biopsy decision in patients with PI-RADS 3 lesions.

Oncological Outcomes of Patients with Non-Clear Cell Renal Cell Cancers: Subtypes of Unclassified and Translocation Renal Cell Cancers.

PURPOSE: We aimed to compare oncological outcomes in the two rare subtypes, unclassified renal cell cancer (unRCC) and translocation RCC (tRCC), vs clear cell RCC (ccRCC). MATERIALS AND METHODS: Between 2004 and 2019, from Turkish Urooncology Society Database, we identified 2324 patients for histological subtypes including 80 unRCC (3.4%), 19 tRCC (0.8%) and 2225 ccRCC (95.8%). RESULTS: The overall (15.8%) and cancer-specific mortalities (11.1%) were found to be higher in tRCC group and the recurrence free mortality (13.8%) was found to be higher in unRCC group. Larger pathological tumor size (p = 0.012) and advanced pathological T stage (p = 0.042) were independent predictive factors on overall mortality in patients with unRCC tumors. CONCLUSION: The oncological outcomes of the unRCC and tRCC are worse than ccRCC and pathological tumor size and pathological stage are predictive factors for mortality in the unRCC.

Comparison of transperineal and transrectal targeted prostate biopsy using Mahalanobis distance matching within propensity score caliper method: A multicenter study of Turkish Urooncology Association.

OBJECTIVE: To compare the clinically significant prostate cancer (csPC)-detecting results of transperineal and transrectal targeted biopsy (TPTB and TRTB, respectively) by performing matching analysis. PATIENTS AND METHODS: This study has used the PC and prostate biopsy database from the Turkish Urooncology Association. A total of 1143 patients with Prostate Imaging-Reporting and Data System (PI-RADS) with ≥3 lesions on multiparametric magnetic resonance imaging (mpMRI) and who had received a software-guided transperineal/transrectal MRI/transrectal ultrasound (TRUS) fusion prostate biopsy with concomitant standard systematic 12-core biopsy were included in this study. csPC detection rates of the TP and TR approaches were compared following Mahalanobis distance matching within propensity score caliper method. The following four variables were selected as covariates for the matching procedure: age, digital rectal examination findings, PSA density, and the index lesion PI-RADS score. RESULTS: The matched sample included 508 TR and 276 TP patients. In both the TP and the TR groups, targeted biopsy was superior to systematic biopsy in detecting csPC (27.5% vs. 24.6%, p < 0.001 and 19.5% vs. 16.3%, p < 0.0001, respectively). Both TPTB and TP systematic biopsy was found to be superior to TRTB and TR systematic biopsy in terms of csPC detection (27.5% vs. 19.5%, p = 0.012 and 24.6% vs. 16.3%, p = 0.006). In patients with an anterior index lesion, an apical index lesion, and a larger prostate, the superiority of TPTB to TRTB was found to be more prominent in terms of csPC detection (37.8% vs. 18.3%, p = 0.044; 34.6% vs. 14.7%, p = 0.002; and 25% vs. 5.1%, p = 0.033, respectively). CONCLUSION: Targeted biopsy was found to be superior to systematic biopsy in detecting csPC in both the TP and the TR approaches. The TP approach is preferred because of its clear superiority in detecting csPC in targeted biopsy, especially in patients with anterior and apical lesions and with larger prostates.

[Comparison of magnetic resonance imaging-transrectal ultrasound fusion prostate biopsy with standard systematic biopsy: A single center experience.] / Comparación de la resonancia magnética biopsia próstata transrectal guiada por ultrasonido con fusión de resonancia magnética con la biopsia próstata sistemática: resultados de un solo centro.

OBJECTIVE: To compare systematic biopsy with MRI-TRUS fusion prostate biopsy in terms of cancer detection rates. PATIENTS AND METHODS: The data of the patients who had a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 or more lesions on mpMRI and underwent MRI-TRUS fusion biopsy with simultaneous 12-core standard systematic biopsy from June 2016 to June 2019 in our tertiary center were retrospectively reviewed. Clinical, radiological and pathological data were recorded. Statistical difference among the groups was determined by using McNemar tests. RESULTS: A total of 344 patients were included in the study. As a result of transrectal targeted and systematic combined biopsy, 117 patients were diagnosed with prostate cancer. Benign pathology rates in patients with PI-RADS 3, PI-RADS 4, and PI-RADS 5 lesions were 93.8%, 68.5%, and 46.4%, respectively. Patients were divided into two groups as ISUP grade 1 and ISUP grade ≥2 and cancer detection rates (CDRs) were found significantly higher in transrectal targeted biopsy compared with the systematic biopsy (12.5% vs. %6.4, p=0.007 and 17.4% vs. 8.7%, p<0.001, respectively). Targeted biopsy CDRs were found significantly higher in the high PSA density group (24.5% vs. 41.4%, p=0.001) unlike the systematic biopsy. CONCLUSION: Transrectal targeted biopsy was superior to systematic biopsy in the diagnosis of prostate cancer. Clinicians should be more selective when making a biopsy decision for patients with PI-RADS 3 lesions. PSA density can be used as a criterion for patient selection for targeted biopsy.

OBJETIVO: Comparar la biopsia sistemática próstata con fusión de resonancia transrectal vs la biopsia prostática sistemática, en términos de detección de cáncer de próstata.PACIENTES Y MÉTODOS: Los datos de pacientes con RNM y PIRADS (Prostate Imaging Reporting and Data System) 3 o más y que recibieron una biopsia prostática transrectal con biopsia simultanea de 12 cilindros sistemática entre junio 2016 y junio 2019 en nuestro centro académico fueron retrospectivamente revisados. Los datos radiológicos, clínicos y patológicos fueron también revisados. La diferencia estadística entre los grupos fue determinada utilizando los tests de McNemar. RESULTADOS: Un total de 344 pacientes fueron incluidos en el estudio. Como resultado de la biopsia transrectal sistemática y dirigida, 117 pacientes fueron diagnosticados de cáncer de próstata. Las tasas de patología benigna en pacientes con PIRADS 3, PIRADS 4 y PIRADS 5 fueron de 93,8%, 68,5%, y 46,4%, respectivamente. Los pacientes fueron divididos en 2 grupos como ISUP grado 1 y ISUP grado 2 o más, las tasas de detección de cáncer fueron superiores en los pacientes que recibieron una biopsia transrectal dirigida vs sistemática (12,5% vs. 6,4%, p=0,007 y 17,4% vs. 8,7%, p<0,001, respectivamente). La detección de cáncer por biopsia dirigida fue superior en pacientes con alta densidad de PSA (24,5% vs. 41,4%, p=0,001) a diferencia de la biopsia sistemática.CONCLUSIÓN: La biopsia transrectal dirigida fue superior a la biopsia sistemática en el diagnóstico de cáncer de próstata. Los clínicos deberían ser más selectivos al tomar la decisión de qué biopsia hacer en un paciente con PIRADS 3. La densidad de PSA se puede utilizar como criterio para realizar una biopsia dirigida.

Comparison of magnetic resonance imaging-transrectal ultrasound fusion prostate biopsy with standard systematic biopsy: a single center experience / Comparación de biopsia de próstata por fusión de imágenes por resonancia magnética-ultrasonido transrectal con biopsia sistemática estándar: experiencia en un solo centro

Objetive: To compare systematic biopsy with MRI-TRUS fusion prostate biopsy in terms ofcancer detection rates. Patients and methods: The data of the patientswho had a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 or more lesions on mpMRI andunderwent MRI-TRUS fusion biopsy with simultaneous12-core standard systematic biopsy from June 2016to June 2019 in our tertiary center were retrospectivelyreviewed. Clinical, radiological and pathological datawere recorded. Statistical difference among the groupswas determined by using McNemar tests. Results: A total of 344 patients were included in thestudy. As a result of transrectal targeted and systematiccombined biopsy, 117 patients were diagnosed withprostate cancer. Benign pathology rates in patients withPI-RADS 3, PI-RADS 4, and PI-RADS 5 lesions were93.8%, 68.5%, and 46.4%, respectively. Patients weredivided into two groups as ISUP grade 1 and ISUP grade≥2 and cancer detection rates (CDRs) were found significantly higher in transrectal targeted biopsy comparedwith the systematic biopsy (12.5% vs. %6.4, p=0.007and 17.4% vs. 8.7%, p<0.001, respectively). Targetedbiopsy CDRs were found significantly higher in the highPSA density group (24.5% vs. 41.4%, p=0.001) unlikethe systematic biopsy. Conclusions: Transrectal targeted biopsy was superior to systematic biopsy in the diagnosis of prostate cancer. Clinicians should be more selective when making abiopsy decision for patients with PI-RADS 3 lesions. PSAdensity can be used as a criterion for patient selectionfor targeted biopsy.(AU)

Objetivo: Comparar la biopsia sistemática próstata con fusión de resonancia transrectal vs labiopsia prostática sistemática, en términos de detecciónde cáncer de próstata. Pacientes y métodos: Los datos de pacientes conRNM y PIRADS (Prostate Imaging Reporting and DataSystem) 3 o más y que recibieron una biopsia prostáticatransrectal con biopsia simultanea de 12 cilindros sistemática entre junio 2016 y junio 2019 en nuestro centroacadémico fueron retrospectivamente revisados. Los datos radiológicos, clínicos y patológicos fueron tambiénrevisados. La diferencia estadística entre los grupos fuedeterminada utilizando los tests de McNemar. Resultados: Un total de 344 pacientes fueron incluidos en el estudio. Como resultado de la biopsiatransrectal sistemática y dirigida, 117 pacientes fuerondiagnosticados de cáncer de próstata. Las tasas de patología benigna en pacientes con PIRADS 3, PIRADS 4y PIRADS 5 fueron de 93,8%, 68,5%, y 46,4%, respectivamente. Los pacientes fueron divididos en 2 gruposcomo ISUP grado 1 y ISUP grado 2 o más, las tasas dedetección de cáncer fueron superiores en los pacientesque recibieron una biopsia transrectal dirigida vs sistemática (12,5% vs. 6,4%, p=0,007 y 17,4% vs. 8,7%,p<0,001, respectivamente). La detección de cáncerpor biopsia dirigida fue superior en pacientes con altadensidad de PSA (24,5% vs. 41,4%, p=0,001) a diferencia de la biopsia sistemática. Conclusion: La biopsia transrectal dirigida fuesuperior a la biopsia sistemática en el diagnóstico decáncer de próstata. Los clínicos deberían ser más selectivos al tomar la decisión de qué biopsia hacer en unpaciente con PIRADS 3. La densidad de PSA se puedeutilizar como criterio para realizar una biopsia dirigida.(AU)

External validation of a prostate cancer nomogram on magnetic resonance/transrectal ultrasound fusion biopsy in men with prior negative systematic biopsy.

OBJECTIVE: To observe how the nomogram, which was created by Truong et al, works in an independent patient group by performing external validation. PATIENTS AND METHODS: One hundred and eighty-one patients who had at least one prior negative 12-core standard systematic biopsy and lesions with PI-RADS scores of 3 or higher that were detected as a result of mpMRI were included in the study. Targeted biopsy with 12-core standard systematic biopsy was performed on all patients. Clinical and pathological features of the patients were recorded. The discrimination, calibration and decision curve analysis were performed to externally validate the nomogram. RESULTS: A total of 181 patients with previous negative 12-core systematic biopsies were analysed. One hundred and thirty-four patients (74%) had benign pathology. Radiological volume and PI-RADS scores of 4 and 5 were found as independent predictors of benign pathology. The area under the curve (CI 95%) was found to be 0.80 (0.73-0.87), indicating good discrimination. The median residual was calculated as -0.0873, the intercept as -0.0690, the slope as 0.8927 and r2 as 0.2586, indicating good calibration. The standardised net benefit of follow-up decisions was found to be 0.54 and 0.36 at the probability threshold of 0.7 and 0.8, respectively. CONCLUSION: The original model showed good discrimination and calibration with our data. Defining a high probability threshold for clinical use would be appropriate for centres with high benign biopsy rates similar to our centre.

Diagnostic accuracy of 68 Ga-PSMA PET/MRI and multiparametric MRI in detecting index tumours in radical prostatectomy specimen.

OBJECTIVE: To evaluate the diagnostic accuracy of the 68 gallium (68 Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) and multiparametric MRI (mpMRI) by region-based comparison of index tumour localisations using histopathological tumour maps of patients who underwent radical prostatectomy because of clinically significant prostate cancer. PATIENTS AND METHODS: The study included 64 patients who underwent radical prostatectomy after primary staging with mpMRI and 68 Ga-PSMA PET/MRI. Diagnostic analysis was performed by dividing the prostate into four anatomic regions as left/right anterior and left/right posterior. The extension of the lesions in mpMRI and the pathological uptake in 68 Ga-PSMA PET/MRI were matched separately for each region with the extension of the index tumour into each region. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the accuracy of mpMRI and 68 Ga-PSMA PET/MRI are shown as 55.7%, 91.8%, 80.6%, 77.2%, 78.1%, and 60.8%, 94.3%, 86.8% 79.8%, 83.5%, respectively. 68 Ga-PSMA PET/MRI has higher sensitivity and specificity compared with mpMRI. However, no statistically significant difference was found (P = .464). Combined imaging had significantly higher diagnostic accuracy compared with mpMRI and 68 Ga-PSMA PET/MRI (change in AUC: 0.084 and 0.046, P < .001 and P = .028, respectively), while no statistically significant difference was found between mpMRI and 68 Ga-PSMA PET/MRI (change in AUC: 0.038, P = .246). CONCLUSION: 68 Ga-PSMA PET/MRI had higher clinical diagnostic accuracy in prostate cancer compared with mpMRI. Diagnostic accuracy was significantly increased in the combined use of both imaging modalities.

Prognostic role of preoperative albumin to globulin ratio in predicting survival of clear cell renal cell carcinoma

ABSTRACT Purpose: To investigate the prognostic role of preoperative albumin/globulin ratio (AGR) in predicting disease-free survival (DFS) and overall survival (OS) in localized and locally advanced clear cell renal cell carcinoma (RCC) patients. Patients and Methods: 162 patients who met the criteria specified were included in the study. The DFS and OS ratios were determined using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors affecting DFS and OS. Results: Median follow-up period was 27.5 (6-89) months. There was a statistically significant relationship between low AGR and high pathological tumor (pT) stage, presence of collecting system invasion, presence of tumor necrosis, and a high platelet count (p = 0.012, p = 0.01, p = 0.001, and p = 0.004, respectively). According to the Kaplan-Meier survival analysis, both OS and DFS were found to be significantly lower in the low AGR group (p = 0.006 and p = 0.012). In the multivariate Cox regression analysis, collecting system invasion and tumor necrosis were found to be independent prognostic factors in predicting OS and pT stage was found to be an independent prognostic factor in predicting DFS (HR: 4.08, p = 0.043; HR: 8.64, p = 0.003 and HR: 7.78, p = 0.041, respectively). Conclusion: In our study, low AGR was found to be associated with increased mortality and disease recurrence in localized and locally advanced RCC.

Prognostic role of preoperative albumin to globulin ratio in predicting survival of clear cell renal cell carcinoma.

PURPOSE: To investigate the prognostic role of preoperative albumin/globulin ratio (AGR) in predicting disease-free survival (DFS) and overall survival (OS) in localized and locally advanced clear cell renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: 162 patients who met the criteria specified were included in the study. The DFS and OS ratios were determined using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors affecting DFS and OS. RESULTS: Median follow-up period was 27.5 (6-89) months. There was a statistically significant relationship between low AGR and high pathological tumor (pT) stage, presence of collecting system invasion, presence of tumor necrosis, and a high platelet count (p = 0.012, p = 0.01, p = 0.001, and p = 0.004, respectively). According to the Kaplan-Meier survival analysis, both OS and DFS were found to be significantly lower in the low AGR group (p = 0.006 and p = 0.012). In the multivariate Cox regression analysis, collecting system invasion and tumor necrosis were found to be independent prognostic factors in predicting OS and pT stage was found to be an independent prognostic factor in predicting DFS (HR: 4.08, p = 0.043; HR: 8.64, p = 0.003 and HR: 7.78, p = 0.041, respectively). CONCLUSION: In our study, low AGR was found to be associated with increased mortality and disease recurrence in localized and locally advanced RCC.