Urological Pathology Grade Research Articles

Impact of ISUP grade group on cancer-specific mortality in radical prostatectomy-treated prostate cancer patients with organ-confined disease

Introduction: We aimed to test the impact of International Society of Urological Pathology (ISUP) grade group (GG) on cancer-specific mortality (CSM) in organ-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP). Methods: RP organ-confined prostate cancer (PCa) patients were identified (Surveillance, Epidemiology, and End Results 2004−2015). Cancer-specific survival (CSS) rates were tested in Kaplan-Meier plots and multivariable Cox regression (MCR) models according to GG: 1–3 vs. 4 vs. 5. Sensitivity analyses addressed GG4 and GG5 patients with available primary and secondary Gleason score (GS). Results: Overall, 61 172 patients with RP organ-confined PCa were identified. Of these, 57 715 (94.4%), 2036 (3.3%) and 1421 (2.3%) harbored GG1–3, 4, and 5, respectively. In Kaplan-Meier analyses, seven-years’ CSS estimates were 99.6 vs. 98.2 vs. 93.8% for GG1–3 vs. 4 vs. 5, respectively (p<0.001). In MCR models, GG4 (hazard ratio [HR] 2.72, p<0.001) and 5 (HR 9.95, p<0.001) independently predicted higher CSM, relative to GG1–3. Furthermore, GG5 also independently predicted higher CSM (HR 3.72, p<0.001) vs. GG4. In sensitivity analyses, 1.2, 1.6, and 2.4 CSM events per 1000 person-years of followup were respectively recorded for GS 4+4, 3+5, and 5+3 patients. Conversely, 4.8 vs. 5.3 CSM events per 1000 person-years of followup were respectively recorded for GS 4+5 vs. 5+4/5+5 patients. Conclusions: In organ-confined PCa, at RP, a small proportion of patients harbor GG4–5. These patients exhibit higher CSM than their GG1–3 counterparts. Moreover, detectable mortality rate differences indicate a dose-response effect according to primary and secondary GS. This phenomenon applies in both GG4 and GG5, as well as between GG4 and GG5.

Prospective validation study of a combined urine and plasma test for predicting high-grade prostate cancer in biopsy naïve men.

Early and accurate diagnosis of prostate cancer (PC) is crucial for effective treatment. Diagnosing clinically insignificant cancers can lead to overdiagnosis and overtreatment, highlighting the importance of accurately selecting patients for further evaluation based on improved risk prediction tools. Novel biomarkers offer promise for enhancing this diagnostic process. In this study, we aimed to externally validate a previously developed urine and plasma biomarker test in a biopsy-naïve population. Urine and blood samples were prospectively collected from 362 biopsy-naïve men with suspected PC before they underwent transrectal prostate biopsies. The expression levels of a 10-gene mRNA panel were quantified using reverse transcription/quantitative polymerase chain reaction of both urine and plasma. These gene expression levels, combined with clinical features and plasma prostate-specific antigen (PSA) levels, were used to predict the presence of International Society of Urological Pathology grade group ≥ 2 PC. Complete data were available for 314 patients. The sensitivity and specificity of the biomarker test were 87% (95% CI: 79-93%) and 42% (95% CI: 36-49%), respectively. The area under the curve was 0.76 (95% CI: 0.7-0.82) for the biomarker test probability and 0.65 (95% CI: 0.59-0.72) for PSA (p = 0.02). The test's negative predictive value was 89% (CI: 81-94%). This study did not replicate the previously reported high accuracy of the biomarker test, highlighting the need for further refinement and robust external validation to ensure reliable performance across diverse patient populations.

MR-guided Transrectal Focal Laser Ablation for Localized Low- and Intermediate Risk Prostate Cancer: Initial Outcomes Using an Integrated Laser Ablation System.

To investigate the feasibility and safety of MRI-guided focal laser ablation (FLA) in localized, International Society of Urological Pathology (ISUP) grade 1-3, prostate cancer (PCa) using an integrated system. Ten consecutive males (mean age: 66±7 years) with low-to-intermediate risk PCa were prospectively included (April 2022-May 2023) and treated with MRI-guided FLA using an integrated system for laser energy control and MR thermometry monitoring. Primary endpoints were technical success, procedure-related adverse events (AEs) following SIR (Society of Interventional Radiology) classification, and 12-months local tumor progression-free survival (LTPFS), defined as no evident residual/ recurrent disease on follow-up imaging or histopathology at the treatment site. Secondary endpoints included MRI-derived percentual volumetric tumor coverage, prostate-specific antigen (PSA), sexual and urinary function response measured by the International Prostate Symptom Score index and Sexual Health Inventory for Men (SHIM) questionnaires. Technical success was achieved in 10/10 (100%) patients (ISUP grade 1 (n=1), 2 (n=8) and 3 (n=1)). Three AEs were observed: urinary tract infection (n=2; SIR grade B) and acute urinary retention (n=1; SIR grade D). Cumulative 12-month LTPFS was 80% (8/10 patients). Median tumor coverage was 100% (IQR: 95-100%). Compared to baseline, the mean PSA level decreased, but did not reach statistical significance (6.6 vs. 4.4 ng/mL; p=0.06), and mean urinary (8.6 vs. 7.3; p=0.60) and sexual function (11.3 vs. 10.5; p=1.00) scores were non-significantly altered at 12 months follow-up. MRI-guided FLA in patients with low-to-intermediate risk PCa using an integrated system was feasible and safe and indicates promising short-term oncological and functional outcomes.

Development and Validation of a Deep Learning Model Based on MRI and Clinical Characteristics to Predict Risk of Prostate Cancer Progression.

Purpose To validate a deep learning (DL) model for predicting the risk of prostate cancer (PCa) progression based on MRI and clinical parameters and compare it with established models. Materials and Methods This retrospective study included 1607 MRI scans of 1143 male patients (median age, 64 years; IQR, 59-68 years) undergoing MRI for suspicion of clinically significant PCa (csPCa) (International Society of Urological Pathology grade > 1) between January 2012 and May 2022 who were negative for csPCa at baseline MRI. A DL model was developed using baseline MRI and clinical parameters (age, prostate-specific antigen [PSA] level, PSA density, and prostate volume) to predict the time to PCa progression (defined as csPCa diagnosis at follow-up). Internal and external testing was performed. The model's ability to predict progression to csPCa was assessed by Cox regression analyses. Predictive performance of the DL model up to 5 years after baseline MRI in comparison with the European Randomized Study of Screening for Prostate Cancer (ERSPC) future-risk calculator, Prostate Cancer Prevention Trial (PCPT) risk calculator, and Prostate Imaging Reporting and Data System (PI-RADS) was assessed using the Harrell C-index. Optimized follow-up intervals were derived from Kaplan-Meier curves. Results DL scores predicted csPCa progression (internal cohort: hazard ratio [HR], 1.97 [95% CI: 1.61, 2.41; P < .001]; external cohort: HR, 1.32 [95% CI: 1.14, 1.55; P < .001]). The model identified a subgroup of patients (approximately 20%) with risks for csPCa of 3% or less, 8% or less, and 18% or less after 1-, 2-, and 4-year follow-up, respectively. DL scores had a C-index of 0.68 (95% CI: 0.63, 0.74) at internal testing and 0.56 (95% CI: 0.51, 0.61) at external testing, outperforming ERSPC and PCPT (both P < .001) at internal testing. Conclusion The DL model accurately predicted PCa progression and provided improved risk estimations, demonstrating its ability to aid in personalized follow-up for low-risk PCa. Keywords: MRI, Prostate Cancer, Deep Learning Supplemental material is available for this article. ©RSNA, 2025.

Impact of neurovascular bundle preservation on biochemical recurrence after robot-assisted radical prostatectomy for high-risk prostate cancer.

To evaluate functional and oncological outcomes in patients who underwent unilateral or bilateral nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) for high-risk prostate cancer. The cohort comprised 2683 patients with clinical stage T1-4, N0M0 high-risk prostate cancer who underwent RARP in Japanese tertiary care centers from August 2011 to April 2023. High risk was defined using the European Association of Urology risk stratification criteria. Patients were classified as high risk if they had clinical stage T2c-T4, a serum prostate-specific antigen concentration (PSA) of > 20ng/dL, or an International Society of Urological Pathology (ISUP) grade of 4-5. Patients were grouped into NS and non-NS surgery groups. Propensity score matching was performed (1:1 ratio) to reduce confounding bias. The primary outcome was biochemical recurrence (BCR)-free survival (BCR-FS). The impact of NS surgery on BCR-FS was examined in the propensity score-matched cohort using Cox proportional hazards regression. The propensity score-matched cohort comprised 1722 patients. In the matched cohort, median follow-up was 31.9months. The 5-year BCR-FS was 70.2% in the NS group and 71.9% in the non-NS group (HR 1.05; 95% confidence interval, 0.85-1.29). NS surgery did not increase the risk of BCR in subgroups of patients stratified according to ISUP grade, T stage, percent cancer core involvement, and PSA. Neurovascular bundle preservation during RARP for high-risk prostate cancer appears feasible without increasing the BCR rate. However, the retrospective study design carries the potential influence of selection bias.

Does bladder outflow obstruction obfuscate the traditional clinical factors that are used to assess the risk of prostate cancer at rapid-access diagnostic clinics?

To understand whether bladder outflow obstruction influences the association between traditional clinical predictive factors, particularly prostate-specific antigen (PSA) density and clinically significant prostate cancer (csPCa). This will help facilitate effective and evidence-based triaging of patients in rapid-access clinics. We retrospectively analysed prospectively collected data from 307 suspected prostate cancer patients who underwent diagnostic biopsy from 2019 to 2023 at a single, high-volume, specialist cancer centre. Uroflowmetry testing generated two cohorts: patients with bladder outflow obstruction and non-obstructed patients. The cohort characteristics between the groups were compared and logistic regression analyses were performed to assess associations between clinical predictive factors (age, PSA density, ethnicity, family history, digital rectal examination, urinary symptom severity and magnetic resonance imaging using the PI-RADS scoring system) and clinically significant prostate cancer (csPCa) on biopsy (defined as International Society of Urological Pathology grade of greater than or equal to two). The obstructed group (n = 80) had significantly larger prostates and worse symptom severity (p < 0.05). There was no significant difference between the other predictive factors or csPCa compared to the non-obstructed (n = 227) cohort. Multivariable logistic regression analysis showed age, PSA density, an abnormal digital rectal examination and scoring PI-RADS 4-5 on magnetic resonance imaging were all significantly associated with csPCa in the non-obstructed cohort (p < 0.05). Contrastingly, only symptom severity and scoring PI-RADS 5 were significantly associated with csPCa for the obstructed patients (p < 0.05). In the presence of bladder outflow obstruction, traditional predictive variables such as age, PSA density, digital rectal examination and scoring PI-RADS 4 are not associated with csPCa. This study suggests that using these predictive variables to triage patients in rapid-access clinics with a patient who has bladder outflow obstruction could lead to the overuse of invasive biopsy.

Radical prostatectomy without prostate biopsy based on a noninvasive diagnostic strategy: a prospective single-center study.

Prostate biopsy is the most common approach for diagnosing prostate cancer (PCa); however, it has inherent limitations, such as the invasive procedure, postoperative complications, and false negative results. We aimed to provide a noninvasive diagnostic strategy for patients with highly suspected PCa and to evaluate the feasibility of performing biopsy-spared radical prostatectomy. This prospective study included a total of 57 patients between November 10, 2022, and December 1, 2023. All 57 patients underwent radical prostatectomy without prior prostate biopsy based on a noninvasive diagnostic strategy consisting of a diagnostic prediction model [comprised of the prostate imaging-reporting and data system (PI-RADS) score and prostate-specific antigen density (PSAD)] and the 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/computed tomography (CT) examination. The primary endpoint was the positive predictive value (PPV) of clinically significant PCa [the International Society of Urological Pathology (ISUP) grade ≥2, Gleason score ≥3 + 4]. The secondary endpoints were a PPV of any-grade PCa (ISUP grade ≥ 1, Gleason score ≥3 + 3) and high-grade PCa (ISUP grade ≥3, Gleason score ≥4 + 3), and the false positive rate of the diagnostic strategy. Of the 371 screened patients with clinically suspected PCa, 57 patients fulfilled the criteria and consented to participate in this study. The median PSAD level was 0.56 (0.42-0.82) ng/mL2; 13 (22.8%) patients were identified as having a PI-RADS score of 4, and 44 (77.2%) patients with a PI-RADS score of 5. The median SUVmax of 18F-PSMA-1007 PET/CT was 21.6 (15.8-33.0). For the 57 enrolled patients who received radical prostatectomy directly, the PPV of clinically significant PCa was 98.2% [56/57, 95% confidence interval (CI): 90.6-100%]. Only 1.8% (1/57, 95% CI: 0.0-9.4%) of patients were diagnosed with clinically insignificant PCa (ISUP grade = 1, Gleason score = 3 + 3). The PPV of any-grade PCa and high-grade PCa were 100% and 73.7% (42/57, 95% CI: 60.3-84.5%), respectively. No one had a false positive result. We proposed a noninvasive diagnostic strategy consisting sequentially of a diagnostic prediction model and the 18F-PSMA-1007 PET/CT examination for diagnosing PCa. Despite some limitations, our initial findings suggest the potential feasibility of radical prostatectomy without prior prostate biopsy.

Oncological Safety of MRI-Informed Biopsy Decision-Making in Men With Suspected Prostate Cancer

The magnetic resonance imaging (MRI) pathway for diagnosing clinically significant prostate cancer (csPCa; defined as International Society of Urological Pathology grade group ≥2) uses multiparametric MRI (mpMRI) for prostate biopsy (PB) decision-making. However, the intermediate impact on patient outcomes in men with negative MRI results avoiding PB and men with positive MRI results without PCa remains unknown. To assess the feasibility and safety of a community-based MRI diagnostic strategy in men with suspected PCa using 3-year active monitoring. This multisite, longitudinal cohort trial took place across 54 community-based urology practices and 2 radiology imaging centers at a referral academic institution in Berlin, Germany. Eligible participants aged 18 to 75 years with clinically suspected PCa were enrolled between September 2016 and December 2017 and monitored for 3 years. Final analysis was reported on December 23, 2023. Participants underwent 3-T mpMRI. Men with findings suspected to be PCa were recommended for targeted PB (diagnostic phase). Men with negative mpMRI results or positive mpMRI results with benign findings at PB were systematically monitored for 3 years (monitoring phase). Clinical visits were recommended every 6 months. The total proportion of men avoiding PB and those with csPCa. A total of 593 men (median [IQR] age, 64 [58-70] years) underwent mpMRI, with 286 (48%) having negative MRI results, 261 (44%) avoiding PB initially, and 242 (41%) avoiding PB over 3 years. csPCa was detected in 161 (27%) men after immediate PB, increasing to 172 (29%) men after 3 years. Seven men with negative MRI results were diagnosed with PCa by immediate PB (including 4 cases of csPCa), while 279 entered monitoring. Three-year monitoring was completed by 233 (84%) men, with 7 diagnoses of csPCa. Of 307 men with positive MRI results, 58 (19%) showed no PCa after immediate PB, of which 41 (71%) completed monitoring and 4 (7%) were diagnosed with csPCa. In this cohort study, men with negative mpMRI results avoiding biopsy were not at elevated risk of csPCa. The study confirms the oncological safety of the prebiopsy MRI strategy of avoiding an immediate PB after negative MRI results when a programmatic safety net is in place.

Comparison of rigid and elastic registration methods in software-based targeted prostate biopsy: a multicenter cohort study.

This study aims to compare the success rates of rigid registration (RR) and elastic registration (ER) systems in diagnosing all cancers and clinically significant prostate cancer (csPC) in software-based targeted prostate biopsies (TPBs) by performing matching analysis. The data of 2061 patients from six centers where software-based TPB is performed were used. All cancer and csPC detection rates of the RR and ER systems were compared following Mahalanobis distance matching with the propensity score caliper method. Logistic regression analysis was applied to identify factors predicting clinically insignificant prostate cancer (ciPC) and csPC diagnoses. Additionally, the International Society of Urological Pathology Grade Group (ISUP GG) upgrade rates of RR and ER systems were compared between biopsy and radical prostatectomy pathologies. The matched sample included 157 RR and 157 ER patients. No statistically significant difference was found between ER and RR in terms of csPC detection rate (28.0% vs. 22.3% respectively, p = 0.242). The detection rate of all cancers by ER compared to RR was found to be significantly higher (54.8% vs. 35.7% respectively p < 0.001,). No statistically significant difference was found between the ER and RR groups regarding pathological upgrade (39.7% vs. 24.2% respectively, p = 0.130). In the logistic regression analysis performed to determine the factors predicting ciPC, decreased prostate volume and ER system use were found to be independent predictive factors. While the detection rate of csPC was similar for the RR and ER systems, the detection rate of all cancers and ciPC was significantly higher with the ER systems.

Prevalence of SPOP and IDH Gene Mutations in Prostate Cancer in a Jordanian Population.

Speckle-type POZ (SPOP) is described as an essential tumor suppressor factor in gastric cancer, colorectal cancer, and prostate cancer (PCa). SPOP gene mutations were reported in primary human PCa. Isocitrate dehydrogenase-1 (IDH1) oncogene mutations were detected in gliomas, acute myeloid leukemia, some benign and malignant cartilaginous tumors, and only 1% of PCa. This study aimed to investigate the prevalence of mutations of SPOP and IDH1 genes in PCa in the Jordanian population. One hundred formalin-fixed paraffin-embedded tissue samples were collected from patients diagnosed with prostate adenocarcinoma. The obtained specimens were subjected to genomic DNA extraction, PCR amplification, and direct sequencing of exons 4, 5, 6, and 7 of the SPOP gene and exon 6 of the IDH1 gene. SPOP gene mutations were found in 17% of PCa cases, while no mutation was detected in the screened exon 6 of the IDH1 gene. Clinicopathological data demonstrated a strong correlation between prostate-specific antigen (PSA) levels and both Gleason score (GS) and the International Society of Urological Pathology (ISUP) grade group (GG). There was no significant correlation between PSA levels and age (p = 0.816) nor there were significant associations for SPOP mutational status with age (p = 0.659), PSA levels (p = 0.395), GS (p = 0.259), and ISUP GG (p = 0.424) in the tested population. The study found a strong correlation between PSA levels and both GS and ISUP GG. It also identified a high frequency (17%) of SPOP gene mutations in Jordanian Arab PCa patients, mainly in exon 7. No IDH1 mutations were detected in exon 6.

Optimization of Extended Pelvic Lymph Node Dissection Side for Prostate Cancer.

This study aimed to show the association between tumor location and laterality of positive lymph nodes by evaluating biopsy and magnetic resonance imaging (MRI) findings, and to optimize the extended pelvic lymph node dissection (ePLND) side for prostate cancer. The study enrolled patients who underwent robot-assisted radical prostatectomy with ePLND. Tumor locations were determined according to International Society of Urological Pathology grade group 4/5 in biopsies and Prostate Imaging-Reporting and Data System category 4/5 in MRI results. The concordance of tumor location lobe and positive lymph node side with the performance of tumor location-guided ePLND for positive lymph node detection was evaluated. For 301 patients who underwent ePLND at Kyushu University Hospital, tumor locations determined by biopsy and MRI findings showed no lesion in 8 (2.7%) patients, unilateral lobe in 223 (74.1%) patients, and bilateral lobe in 70 (23.3%) patients. The accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were 99.6% and 97.3%, respectively. Among the patients at St. Luke's International Hospital, the accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were estimated to be 99.0% and 97.3%, respectively. This study proposed tumor location-guided ePLND according to biopsy and MRI findings. This novel strategy is expected to reduce the burden of bilateral ePLND at the cost of acceptable risk of failing to detect positive lymph nodes.

Transperineal 3D fusion imaging-guided targeted microwaves ablation for low to intermediate-risk prostate cancer: results of a phase I-II study

Background Targeted microwave ablation (TMA) is a novel modality of focal therapy to treat localized prostate cancer (PCa). We evaluated its short-term functional and oncologic outcomes. Method We performed a single-center, prospective, interventional phase I-II pilot trial (NCT04627896). TMA was performed in 11 patients with a single intracapsular MRI-visible lesion ≤12 mm, International Society of Urological Pathology (ISUP) grade ≤ 2, Prostate Specific Antigen (PSA) < 20 ng/mL, and a 5-mm safety distance from apex and rectum. Patients were treated with a 12 W very low-loss microwaves ablation system, guided by 3D ultrasound/MRI fusion imaging. Follow-up consisted in clinical visits, PSA and validated questionnaires. MRI was scheduled at five months and rebiopsy at six months. The primary endpoints of study were safety and efficacy (absence of tumour in the treated area). Results No severe complications were reported. All patients were discharged the same day of treatment without bladder catheter. No significant changes in PSA or questionnaires scores were reported. At rebiopsy, no cancer was found in five patients (45%); eight patients (73%) had an absence of in-field PCa and nine patients (82%) had an absence of in-field ISUP ≥ 2 PCa. New cancer foci outside the treated area were found in three patients (27%). Limitations of this study were the very limited sample size, the short follow-up, and the lack of a comparator. Conclusions TMA guided by fusion imaging is a safe modality with good ablative efficacy.

Utility of PSA free-to-total ratio for clinically significant prostate cancer in men with a PSA level of

To investigate the relationship between the prostate-specific antigen (PSA) free-to-total ratio (FTR) and International Society of Urological Pathology Grade Group ≥2, clinically significant prostate cancer (csPCa) in men with a low PSA level (≤4 ng/mL). Patients and Methods Data were obtained from the Prostate Cancer Prevention Trial. Patients with a PSA level of ≤4 ng/mL and who received a biopsy within a year of this PSA measurement were included. Associations between FTR and csPCa were investigated with logistic regression, adjusting for age and PSA, a re-scaled Brier score (index of predictive accuracy), and decision curve analysis. A total of 406 patients were analysed with 139 (34%) having csPCa and 204 (50%) having any grade PCa. For those with an FTR ≤0.15, 46% had csPCa, vs 22% for those with a ratio ≥0.20. In a regression model, the predicted probability of csPCa for a 60-year-old with a PSA of 3 ng/mL was 61% if the FTR was 0.05, falling to 18% if the FTR was 0.30. A clear negative relationship between increasing FTR and probability of csPCa was observed. A model containing FTR additional to PSA and age provides greater net benefit as per decision curve analysis and likely superior discrimination and calibration measured by a higher index of predictive accuracy. In middle-aged men with a PSA level between 1.5 and 4 ng/mL but otherwise indicated for biopsy, a low FTR is associated with higher rates of csPCa. It should be utilised as an additional, readily available and inexpensive test to improve prediction of csPCa and aid in patient counselling.

The value of radiomics based on 2-[18 F]FDG PET/CT in predicting WHO/ISUP grade of clear cell renal cell carcinoma

BackgroundThe aim is to develop and validate radiomics based on 2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) parameters for predicting the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of clear cell renal cell carcinoma (ccRCC).MethodsA total of 209 patients with 214 lesions, who underwent 2-[18F]FDG PET/CT scans between December 2016 to December 2023, were included in our study. All ccRCC lesions were categorized into low grade (WHO/ISUP grade I-II) and high grade (WHO/ISUP grade III-IV). The lesions were allocated into a training group and a testing group in a ratio of 7:3. The radiomics features were extracted by a serious of maximum standardized uptake value (SUVmax) thresholds (0,2.5%,25%,40%) with the utilization of the minimum redundancy and maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithm. The clinical, radiomics and combined models were constructed. The receiver operating characteristic (ROC) curve, decision curve and calibration curves were plotted to assess the predicting performance.ResultsThe area under curve (AUC) of PET-0, PET-2.5%, PET-25%, PET-40% model in the training group were 0.881(95% CI: 0.822–0.940),0.883(95% CI: 0.825–0.942),0.889(95% CI: 0.831–0.946),0.887(95% CI: 0.826–0.948); and 0.878(95% CI: 0.777–0.978),0.876(95% CI: 0.776–0.977),0.871(95% CI: 0.769–0.972),0.882(95% CI: 0.786–0.979) in the testing group. Due to perfect prediction and verification performance, the volume of interest (VOI) from PET images with SUVmax threshold of 40% were selected to construct the radiomics model and combined model. The AUC of the clinical model and radiomics model was 0.859 (sensitivity = 0.846, specificity = 0.747) and 0.909 (sensitivity = 0.808, specificity = 0.751) in the training group, respectively; 0.882 (sensitivity = 0.857, specificity = 0.857) and 0.901 (sensitivity = 0.905, specificity = 0.833) in the testing group, respectively. In combined models, the AUC was 0.916, the sensitivity was 0.923 and the specificity was 0.808 in the training group; the AUC was 0.916, the sensitivity was 0.881 and the specificity was 0.792 in the training group.ConclusionRadiomics based on 2-[18F]FDG PET/CT can be helpful to predict WHO/ISUP grade of ccRCC.

Multimodal approach to optimize biopsy decision-making for PI-RADS 3 lesions on multiparametric MRI

PurposeTo develop and evaluate a multimodal approach including clinical parameters and biparametric MRI-based artificial intelligence (AI) model for determining the necessity of prostate biopsy in patients with PI-RADS 3 lesions. MethodsThis retrospective study included a prospectively recruited patient cohort with PI-RADS 3 lesions who underwent prostate MRI and MRI/US fusion-guided biopsy between April 2019 and February 2024 in a single institution. The study examined demographic data, PSA and PSA density (PSAD) levels, prostate volumes, prospective PI-RADS v2.1-compliant interpretations of a genitourinary radiologist, lesion characteristics, history of prior biopsies, and AI evaluations, focusing mainly on the detection of clinically significant prostate cancer (csPCa) (International Society of Urological Pathology grade group ≥2) on MRI/US fusion-guided biopsy. The AI model lesion segmentations were compared to manual segmentations and biopsy results. The statistical methods employed included Fisher's exact test and logistic regression. ResultsThe cohort was comprised of 248 patients with 312 PI-RADS 3 lesions in total (n = 268 non-csPCa, n = 44 csPCa). The AI model's negative predictive value (NPV) was 89.2 % for csPCa in all lesions. In patient-level analysis, the NPV was 91.2 % for patients with a highest PI-RADS score of 3. PSAD was a significant predictor of csPCa (odds ratio = 5.8, p = 0.038). Combining AI and PSAD, where AI correctly mapped a lesion or PSAD ≥0.15 ng/mL2, achieved higher sensitivity (77.8 %) while maintaining a high NPV (93.1 %). ConclusionCombining AI and PSAD has the potential to enhance biopsy decision-making for PI-RADS 3 lesions by minimizing missed csPCa occurrences and reducing unnecessary biopsies.

The prognostic implications and oncogenic role of NSUN5 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC), a predominant form of urinary malignancy, requires the identification of reliable biomarkers to enhance both prognostic outcomes and therapeutic developments specific to ccRCC. NSUN5, a member of the NOL1/NOP2/SUN domain (NSUN) family, plays a critical role in RNA stabilization and exhibits widespread expression across various tumor types. However, the exact function of NSUN5 in ccRCC remains insufficiently understood. Data were collated from cohorts of ccRCC patients who underwent nephrectomy, including those from the Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC), to evaluate the clinical relevance of NSUN5. Integrative models based on NSUN5 expression were subsequently developed to predict the prognosis of ccRCC within the TCGA and SYSUCC cohorts. Furthermore, the impact of NSUN5 on RCC cells and its association with cellular senescence were corroborated through in vitro experimental analyses. NSUN5 exhibited elevated expression in both ccRCC patients and renal cancer cell lines, whose upregulation significantly correlated with age, tumor size, TNM stage, WHO/International Society of Urological Pathology (ISUP) grade, presence of necrosis, and a poor prognosis. An accessible nomogram, incorporating NSUN5 along with various clinicopathological parameters, was adept at predicting outcomes for ccRCC patients. Additionally, in vitro findings indicated that reduced expression of NSUN5 enhanced tumor cell senescence and simultaneously inhibiting cell proliferation and migration. These observations suggest that elevated NSUN5 expression is linked to poorer overall survival (OS) and progression-free survival (PFS), positioning NSUN5 as a viable diagnostic and prognostic biomarker in ccRCC.

Enhancing bone metastasis prediction in prostate cancer using quantitative mpMRI features, ISUP grade and PSA density: a machine learning approach.

Bone metastasis is a critical complication in prostate cancer, significantly impacting patient prognosis and quality of life. This study aims to enhance bone metastasis prediction using machine learning (ML) techniques by integrating dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion features, International Society of Urological Pathology (ISUP) grade, and prostate-specific antigen (PSA) density. A retrospective analysis was conducted on 122 patients with histopathologically confirmed prostate cancer who underwent multiparametric prostate magnetic resonance imaging (mpMRI). Quantitative mpMRI features, PSA density, and ISUP grades were extracted and normalized. The dataset was balanced using oversampling and divided into training (70%) and test (30%) sets. Various ML models were developed and evaluated using area under the curve (AUC) metrics. Bone metastases were present in 26 patients (21.3%) at diagnosis. IAUGC and MaxSlope showed a statistically significant association with bone metastasis (p = 0.035, p = 0.050 respectively). The optimal PSA density cut-off value of 0.24 yielded a sensitivity of 0.88, specificity of 0.60, and AUC of 0.77. Machine learning models were developed using the dataset created with IAUGC, MaxSlope, ISUP grade, and PSA density values. Among the ML models, XGBoost demonstrated superior performance with validation and test AUCs of 91.5% and 92.6%, respectively, along with high precision (93.3%) and recall (93.1%). Integrating quantitative mpMRI features, ISUP grade, and PSA density through machine learning algorithms, particularly XGBoost, significantly improves the accuracy of bone metastasis prediction in prostate cancer patients. This approach can potentially reduce the need for additional imaging modalities and associated radiation exposure.

The impact of age on clinicopathological features and treatment results in patients with localised prostate cancer receiving definitive radiotherapy.

This study assessed the biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), overall survival (OS), and side effects in patients aged < 70 and ≥ 70 years following definitive radiotherapy (RT). It also analysed the correlation between age at diagnosis and clinicopathological characteristics of prostate cancer (PCa). The prognostic factors for bDFS, PCSS, and OS were determined through univariable and multivariable analyses. Two age groups were also compared in terms of acute and late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities, the predictors of which were determined through logistic regression analysis. Of the 1,328 patients, 715 (53.8%) and 613 (46.2%) were aged < 70 and ≥ 70 years, respectively. Median follow-up time was 84.5 months. No significant differences in the 7-year bDFS (86.3% vs. 86.8%) and PCSS rates (92.9% vs. 93.3%) were found between the ≥ 70 and < 70 age groups. The multivariable analysis showed that advanced clinical T stage, high International Society of Urological Pathology (ISUP) grade, and high-risk disease independently predicted poor bDFS and PCSS. Metastatic lymph nodes were another bDFS prognostic factor. The multivariable analysis identified age ≥ 70 years, cardiac events at diagnosis, advanced stage, higher ISUP grade, and non-use of simultaneous integrated boost technique as negative factors for OS. Additionally, diabetes and transurethral resection of the prostate (TUR-P) independently predict late-grade ≥ 2 GU toxicity. Definitive RT is a safe and effective treatment for patients with localised PCa no matter their age. Although patients over 70 years have higher risk factors and comorbidities, their bDFS, PCSS, and toxicities were comparable to those of patients aged < 70 years.

Nomogram Analysis for Predicting Response to Androgen-Receptor-Axis-Targeted Therapies in Patients With Metastatic Castration-Resistant Prostate Cancer.

This study aimed to identify the clinical predictors for the response of patients with mCRPC to ARATs. We retrospectively collected data on consecutive patients who were diagnosed with mCRPC and underwent ARAT treatment during this stage of the disease. Clinical parameters were obtained through medical chart reviews. ARAT failure was defined as a continuous increase in the serum prostate-specific antigen (PSA) level above nadir to > 2 ng/mL, accompanied by radiographic progression. ARAT failure-free survival and overall survival were assessed through Kaplan-Meier survival analysis and Cox regression survival analysis. Nomogram analysis based on significant predictors of ARAT failure-free survival was performed. In total, 319 patients with mCRPC who underwent ARAT were included. Multivariate analysis revealed that age, International Society of Urological Pathology (ISUP) grading, and chemotherapy-naïve status were significant predictors of ARAT failure-free survival. For overall survival, age, ISUP grading, and nadir PSA level during androgen deprivation therapy (ADT) were significant predictors. Through nomogram analysis based on age, ISUP grading, and chemotherapy-naïve status, the likelihood of ARAT duration being more or less than 1 year could be predicted. For mCRPC patients, being older, having ISUP Grade 5 cancer, and having a history of chemotherapy were associated with a shorter duration of response to next-line ARATs. Therefore, other therapeutic agents should be prioritized for such patients. Notably, among the included patients, those who were older, had a higher ISUP grade and a higher nadir PSA level during ADT exhibited worse overall survival.

Active Surveillance as Preferred Treatment for ISUP Grade I Prostate Cancer: Confronting the ProtecT Trial.

The advantages of active surveillance (AS) in low-risk prostate cancer (PC) have already been widely demonstrated. The 15-year results of the Prostate Testing for Cancer and Treatment (ProtecT) trial were published recently, reflecting worse oncological outcomes of their active monitoring programme (AMP) compared with radical prostatectomy (RP) or radiotherapy (RDT). Our objective was to analyse the survival of patients with International Society of Urological Pathology (ISUP) grade I PC depending on the treatment received and point out the differences between an AS protocol and the AMP established in the ProtecT trial. A retrospective study of patients with ISUP grade I PC managed by AS, RP or RDT was conducted. A comparative intention-to-treat survival analysis was performed. Our AS protocol included routine 18-core surveillance biopsies of all patients. On the basis of this assumption, the patients included in AS were divided into two groups: Those who met the rebiopsy criteria of the ProtecT trial and those who should not have been biopsied in accordance with this trial. Of the total 2865 patients, 981 met the selection criteria with a median follow-up of 7.7 years: 448 (45.7%) in AS, 399 (40.7%) in RP and 134 (13.7%) in RDT. The median age at diagnosis was 66.9, 63.2 and 69.2 years, respectively. The AS and RP groups were comparable in all the variables. The overall and cancer-specific survival results were similar, but the AS group had better metastasis-free survival. The RDT group presented worse clinical features in prostate-specific antigen and stage and worse survival outcomes compared with the other groups (p < 0.005). Out of the 448 patients included in AS, 100 met some of the criteria for rebiopsy of the ProtecT trial. Amongst the 348 patients who did not meet any criteria, 138 (39.6%) ended up receiving active treatment due to Gleason progression, increasing number of positive cores or both in the majority of cases (94.4%). Surveillance biopsy is a major factor that contributes to achieving good oncological results in AS. Active monitoring is not comparable with an AS protocol, and thus, the results of the ProtecT trial are poorly assessable.