Search Results (941)

The complex relationship between human cytomegalovirus (HCMV) and cancer has been of interest since the 1960s. As a highly prevalent human β-herpesvirus, HCMV establishes lifelong latency in CD34+ myeloid progenitor cells and has been implicated as an oncomodulatory virus in various cancers, including glioblastoma multiforme, breast, prostate, colorectal, and ovarian cancer (OC). Recently, discussions have emerged regarding the classification of HCMV as an eighth oncovirus due to the persistence of its nucleic acids and proteins in many tumour types. As one of the deadliest gynaecological cancers, OC is often characterised as the ‘silent killer’ with less than half of women surviving for 5 years, a rate that drops below 20% when detected at advanced stages. Reported effects of HCMV vary between cancers, likely due to differences in tumour type, viral strain, and disease stage. While HCMV infection has been linked to poor OC patient outcomes, its impact on the OC tumour microenvironment (TME) and immune system remains less understood. Investigating HCMV’s potential oncogenic role could provide critical insights into OC progression. This review discusses recent developments on HCMV’s multifaceted roles in OC, including strain heterogeneity, immunomodulation of the TME, dysregulation of inflammatory signalling pathways, and potential therapeutic approaches targeting HCMV in anti-cancer immunotherapies. Full article

Background: Non-muscle-invasive bladder cancer (NMIBC) represents approximately 70–75% of newly diagnosed bladder cancers and is characterized by high recurrence rates despite guideline-based management. Chronic urinary retention and bladder outlet obstruction (BOO) have been proposed as under-recognized modifiers of NMIBC outcomes through prolonged exposure to urinary carcinogens, inflammation, and altered intravesical pharmacokinetics. This narrative review qualitatively synthesizes biological and clinical evidence linking BOO-related dysfunction with NMIBC behavior and explores the emerging, but preliminary, role of Holmium Laser Enucleation of the Prostate (HoLEP) as a functional adjunct in selected patients. Methods: A narrative review was conducted according to SANRA guidelines. PubMed/MEDLINE, Embase, and Scopus were searched (January 2000–October 2025) using predefined terms for NMIBC, BOO, urinary retention, and HoLEP. Two reviewers independently screened records, with disagreements resolved by consensus. Sixty-one studies met inclusion criteria. Results: Elevated postvoid residual (PVR) (>80–100 mL) and moderate to severe lower urinary tract symptoms (LUTS) were consistently associated with higher NMIBC recurrence rates, independent of tumor stage and grade, in heterogeneous cohorts. Retention correlated with reduced efficacy of Bacillus Calmette–Guérin (BCG) and mitomycin C, likely via uneven drug distribution and a chronically inflamed urothelium. Mechanistic data support a plausible link between BOO-related inflammation, barrier dysfunction, and tumor biology, although direct biomarker correlations with PVR or pharmacokinetic studies are lacking. HoLEP provides durable relief of BOO, reduces PVR, and improves LUTS. Limited retrospective data suggest an association between HoLEP and lower recurrence, but these observations are confounded and should be viewed as hypothesis-generating. Conclusions: Chronic urinary retention and BOO appear to be modifiable functional factors that may influence NMIBC recurrence and intravesical therapy performance. HoLEP is a promising option to optimize bladder emptying in carefully selected patients, but its oncologic impact remains unproven and should be considered hypothesis-generating pending prospective, risk-adjusted studies. Full article

Prostate cancer is the most diagnosed cancer among Canadian men, except non-melanoma skin cancers. Prostate-specific antigen (PSA) screening can enable early detection, but it is not formally recommended in Canada. Nonetheless, opportunistic screening persists, influenced by US practices and some Canadian guidelines that support screening. This study provides a detailed analysis of trends in prostate cancer incidence, mortality, stage distribution, and net survival in the context of evolving PSA screening guidelines. Prostate cancer case (1984–2022) and death (1984–2023) data were primarily from the Canadian Cancer Registry and the Canadian Vital Statistics Death database, respectively. Joinpoint regression identified incidence and mortality trends. Net survival was determined using the Pohar Perme estimator. Following the introduction of PSA screening, the prostate cancer age-standardized incidence rate among men aged 50–74 increased 1.8% annually until 2007 (p = 0.006) before declining at an annualized rate of −5.9% (p = 0.005) until 2014. Among men aged ≥75, incidence declined at −3.2% annually from 1992 to 2015 (p < 0.001). The prostate cancer age-standardized mortality rate (ASMR) among men aged 50–74 fell at an annualized rate of −4.3% between 1994 and 2010 (p = 0.022), but the decline slowed thereafter. The ASMR among men aged ≥75 continuously declined after a peak in 1995, with the greatest change noted before 2012. From 2010 to 2017, stage IV prostate cancer incidence increased across all 10-year age groups, peaking among men aged 60–69 at 4.1% annually (p < 0.001). Among men aged 50–74, the corresponding annualized increase was 3.7% (p = 0.010), while among men aged ≥75, it was 3.1% (p < 0.001). Although stage IV net survival among men aged 50–74 increased from 49.4% in 2010–2011 to 56.6% in 2016–2017, all-stage net survival declined slightly after 2011, concurrent with a shift towards a greater proportion of stage IV cases. Prostate cancer outcomes in Canada reflect US PSA screening recommendations. Organized and thoughtful screening may represent an opportunity to decrease the rising late-stage incidence. Full article

Prostate cancer remains one of the most prevalent malignancies among men worldwide, with late-stage diagnosis contributing significantly to mortality rates. In this study, we report the development of a graphene oxide (GO)-based QCM biosensor for the early and sensitive detection of Prostate Cancer Antigen 3 (PCA3), a biomarker with higher specificity than conventional PSA tests. The sensor interface was fabricated via a layer-by-layer approach of L-cysteine, GO, and a capture probe onto a gold electrode, resulting in enhanced surface area and biomolecular recognition capacity. Structural and morphological characterizations using XRD, FE-SEM, AFM, and FT-IR confirmed the successful and uniform integration of GO and functional layers. Optimization of fabrication parameters, including EDC-NHS activation time, capture probe concentration, and target incubation time, was performed to achieve maximum sensitivity and binding efficiency. The biosensor demonstrated a distinct, concentration-dependent frequency shift upon hybridization with PCA3 targets over a range of 1.00 fM to 1.00 μM, with a calculated limit of detection (LOD) of 0.268 nM and a rapid response time of 20 min. These results underscore the potential of GO-modified QCM platforms for highly sensitive, rapid, and portable diagnostics, not only for prostate cancer screening but also for broader clinical applications involving biomarkers. Full article

Background/Objectives: Prostate cancer is the most prevalent malignancy in men and remains a leading cause of cancer-related mortality worldwide. Conventional imaging modalities exhibit limited sensitivity, particularly in the context of disease recurrence and advanced disease. Methods: A narrative review was conducted of studies published between 2015 and 2025, identified through PubMed, Embase, and Cochrane. Eligible publications addressed advanced imaging techniques, PSMA-targeted diagnostics and therapies, radiogenomics, liquid biopsy approaches, and artificial intelligence applications and personalized medicine. Preclinical studies, single case reports, and conference abstracts without full text were excluded. Results: PSMA PET/CT outperforms conventional imaging for detection, and restaging, influencing clinical management across disease stages. Lutetium-177–PSMA-617 has become the standard radioligand therapy for metastatic castration-resistant prostate cancer, whereas alpha-emitting agents remain under clinical investigation. Radiogenomics and liquid biopsy assays (ctDNA, CTCs, AR-V7) provide complementary molecular insights. Artificial intelligence enhances imaging interpretations, standardization, and reproducibility, while multimodal data integration supports individualized risk stratification. Integrative models combining imaging, genomic, and liquid biopsy data pave the way toward precision oncology and personalized therapeutic decision-making. Conclusions: Advances in imaging and theragnostics are reshaping prostate cancer management, bridging the gap between molecular biology and clinical practice to enable precision oncology. Full article

Introduction/Background: Treatment of localized prostate cancer includes radical prostatectomy (RP) with or without pelvic lymph node dissection (PLND). While multiple guidelines recommend PLND for staging purposes, recent data has shown questionable therapeutic benefit. Thus, understanding the morbidity associated with PLND is important for counseling patients. We used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted prostatectomy database to quantify real-world 30-day postoperative outcomes of patients undergoing contemporary robot-assisted PLND at the time of RP for prostate cancer to quantify the incremental morbidity. Methods: We conducted a retrospective cohort study using the NSQIP database of adult patients undergoing radical prostatectomy from 2019 to 2022. The primary outcomes were procedure-specific outcomes such as lymphocele and rectal injury. Secondary outcomes included a composite of any of the following 30-day major postoperative outcomes: mortality, reoperation, cardiac or neurologic event, as well as the individual components of this outcome, as well as infectious and other complications. We also analyzed yearly trends associated with PLND. Groups were balanced using propensity score matching (PSM) with a 1:1 ratio using demographic characteristics, prior medical history, and cancer staging data. Likelihood of complications was assessed by conditional logistic regression. Results: We identified 13,413 patients between 2019 and 2022 who underwent robotic prostatectomy: 11,341 (85%) had PLND while 2072 (15%) did not. After PSM, our cohort included 2071 matched pairs of patients with and without PLND. Patients who underwent PLND were more likely to be diagnosed with lymphocele (2.14% vs. 0.68%, OR 4.17; 95% CI 2.00, 8.68), have unplanned readmission (4.22% vs. 3.27%, OR 1.31; 95% CI 1.03, 1.65), and develop organ-site/space SSI (1.18% vs. 0.60%) (OR 1.97, 95% CI 1.20, 3.23). There was no significant association between the receipt of PLND and the likelihood of urinary leak or fistula, or ureteral obstruction. There were no significant differences between the two groups with respect to secondary outcomes of interest. Conclusion: Contemporary robotic PLND is associated with a 3-fold increased likelihood of lymphocele, as well as increased likelihood of unplanned readmission and organ-site SSI, though no significant differences in major postoperative complications were identified. We found that the odds of lymphoceles, readmission, and SSI in our study are lower than previously reported. These data provide real-world data to guide patient counseling and optimize patient selection for PLND at the time of RALP. Full article

Yukon residents often must travel long distances to access specialized cancer care, which may impact cancer treatment patterns. We conducted a retrospective study to characterize all adult breast, prostate, colorectal, and lung cancer cases from the Yukon, diagnosed from 2009 to 2021 and seen in consultation at BC Cancer. We collected data on demographics, tumour characteristics and treatment, including timepoints for cancer care. A secondary analysis of non-referred cases was conducted. There were a total of 336 breast, 270 prostate, 279 colorectal and 266 lung cancer cases diagnosed in the Yukon from 2009 to 2021, of which 298 (88.7%), 120 (44.4%), 206 (73.8%) and 204 (76.7%) cases were referred to BC Cancer, and 266 (79.2%), 118 (43.7%), 204 (73.1%) and 183 (68.8%) were included in this study, respectively. Most cases were diagnosed at an early stage (breast: 92.9%, prostate: 82.2%, colorectal: 72.1%, lung: 45.9%). Nearly 70% of cases resided in Whitehorse (Yukon’s capital), where most Yukon residents live. Compared to available published Canadian timepoints, Yukon patients had similar or shorter wait times in 13 of 22 timepoints along the pathway to diagnosis and treatment. However, time from biopsy to surgery had the longest relative wait times across all tumour groups (range: 26–60% longer). Our study provides baseline data that can help inform cancer care provision for Yukon residents. Full article

Background: Considering the high global frequency of prostate cancer, it is necessary to know the benefits and drawbacks of numerous diagnostic and therapeutic modalities. Methods: In this article, we include 88 manuscripts (46/88 original studies) found on PubMed, written in English in extenso, dealing with nuclear medicine methods in patients with prostate cancer. Results: Choline PET/CT had low sensitivity in detecting the primary tumor. This method has been almost completely replaced by PSMA PET/CT, which is included in international guidelines and recommended for initial staging of unfavorable intermediate- to high-risk prostate cancer, the detection of recurrent disease after treatment, the evaluation of mCRPC, therapy response evaluation, and theranostics. FDG is currently used in aggressive forms of prostate cancer and as a supplement in PSMA PET/CT for patient selection for RLT. Na[¹⁸F]F has demonstrated satisfactory diagnostic capacity for evaluating bone loss; however, due to a lack of research, it is not recommended in international guidelines. ¹⁸F-Fluciclovine has lower sensitivity than [¹⁸F]F-PSMA-1007 for the detection of early biochemical recurrence in prostate cancer. GRPR and SSTR analogs are less frequently used but can be useful in the evaluation of rarer pathohistological types. [^99mTc]Tc-PSMA can be used in resource-limited settings where PET/CT is unavailable, with a lower sensitivity compared to [¹⁸F]F-PSMA-1007 but a higher sensitivity compared to bone scans. Conclusions: PSMA tracers are important tools for evaluating intermediate- and high-risk prostate cancer, with limitations in 5–10% of prostate cancers that do not express PSMA. Theranostics are increasingly incorporating PSMA. Full article

Prostate cancer (PCa) is the second most common cancer in men, and it is frequently diagnosed at an advanced stage of the disease. Androgen Deprivation Therapy (ADT) has traditionally represented the backbone of therapy for high-risk, recurrent, and metastatic disease; however, in the last ten years a new group of molecules known as androgen receptor pathway inhibitors (ARPIs) have been demonstrated to improve outcomes in metastatic patients when added to ADT. Developed and validated originally in the setting of castration-resistant disease, ARPIs have been implemented progressively earlier in the natural history of PCa, involving patients who have never received ADT before or that are still responsive to this treatment. Considering the strong evidence for treatment intensification in patients with high-risk features, with this review we aim to provide a complete overview of the current indications for the use of ARPIs through all the stages of castration-sensitive prostate cancer (CSPC). Full article

Background/Objectives: Metformin is one of the most frequently used concomitant medications among prostate cancer (PCa) patients. However, the effects of metformin on all-cause and PCa-specific mortality among men diagnosed with advanced/metastatic PCa treated with androgen-deprivation therapy (ADT) remain poorly understood, but they may be specifically explained by emulating a target trial. Methods: We emulated a target trial of metformin therapy and survival using observational data on 7361 patients diagnosed with advanced PCa, who were treated with ADT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2008–2019), with completed follow-up until 2020. We included patients with diabetes, and participants were assigned as either “initiator of metformin within 6 months after advanced PCa diagnosis” or “non-initiator of metformin.” We estimated mortality risks using Cox proportional hazards models with adjustment for risk factors via inverse probability weighting using both intention-to-treat and per-protocol analyses. Results: Over 13 years of follow-up, with a maximum 3 years of follow-up after PCa diagnosis, all-cause mortality occurred in 52 metformin initiators (47.7%) versus 3052 non-initiators (42.1%), while PCa-specific mortality occurred in 36 initiators (33.0%) versus 1919 non-initiators (26.5%). In the intention-to-treat analysis, metformin initiation was not associated with all-cause mortality (Hazard Ratio [HR] = 1.38, 95% CI: 0.98–1.95) or PCa-specific mortality (HR = 0.99, 95% CI: 0.63–1.55). Similarly, in per-protocol analysis, there was no evidence of risk reduction with all-cause (HR = 1.20, 95% CI = 0.80–1.81) or PCa-specific mortality (HR = 1.45, 95% CI = 0.88–2.38) after adjusting for time-varying covariates and allowing a 30-day gap for metformin discontinuation, adjusted for via inverse probability weighting. Conclusions: Our findings align with prior randomized trials showing no survival benefit of metformin in advanced PCa patients receiving ADT. Timing of metformin discontinuation also showed no significant effect. However, the small size of the metformin initiator group precluded subgroup analyses for hormone-sensitive (HSPC) and castrate-resistant prostate cancer (CRPC), limiting our ability to explore potential differential effects. Full article

Prostate cancer is one of the leading causes of cancer-related morbidity and mortality worldwide, and imaging plays a critical role in its detection, localization, staging, treatment, and management. The advent of artificial intelligence (AI) has introduced transformative possibilities in prostate imaging, offering enhanced accuracy, efficiency, and consistency. This review explores the integration of AI in prostate cancer diagnostics across key imaging modalities, including multiparametric MRI (mpMRI), PSMA PET/CT, and transrectal ultrasound (TRUS). Advanced AI technologies, such as machine learning, deep learning, and radiomics, are being applied for lesion detection, risk stratification, segmentation, biopsy targeting, and treatment planning. AI-augmented systems have demonstrated the ability to support PI-RADS scoring, automate prostate and tumor segmentation, guide targeted biopsies, and optimize radiation therapy. Despite promising performance, challenges persist regarding data heterogeneity, algorithm generalizability, ethical considerations, and clinical implementation. Looking ahead, multimodal AI models integrating imaging, genomics, and clinical data hold promise for advancing precision medicine in prostate cancer care and assisting clinicians, particularly in underserved regions with limited access to specialists. Continued multidisciplinary collaboration will be essential to translate these innovations into evidence-based practice. This article explores current AI applications and future directions that are transforming prostate imaging and patient care. Full article

Cancer metabolomics has become a powerful way of understanding tumor biology, identifying biomarkers and metabolites, and helping precision oncology. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), among many other analytical platforms, has gained popularity over the past two and a half decades due to its unique ability of directly analyzing metabolites in tissue with spatial resolution. This review will study 2000–2025 MALDI-based strategies for cancer metabolite detection, spanning from early proof-of-concept protein profiling to the development of high-resolution MALDI-MS imaging (MALDI-MSI), which is capable of mapping thousands of metabolites at near single-cell resolution. Its applications include the differentiation of tumor versus normal tissue, discovery of stage and subtype specific biomarkers, mapping of metabolic heterogeneity, and the visualization of drug metabolism in situ. Breakthrough technological milestones, such as the advanced matrices, on-tissue derivatization, MALDI-2 post-ionization, and the integration with Orbitrap or Fourier-transform ion cyclotron resonance (FT-ICR) platforms, have significantly improved the overall sensitivity, metabolite coverage, and spatial fidelity. Clinically, MALDI-MS has shown its purpose in breast, prostate, colorectal, lung, and liver cancers by providing metabolic fingerprints that are linked to tumor microenvironments, hypoxia, and therapeutic response. However, challenges such as the inclusion of matrix interface with low-mass metabolites, limited quantitation, ion suppression, and the lack of standardized procedures do not yet allow for the transition from translation to routine diagnostics. Even with these hurdles, the future of MALDI-MS in oncology remains in a good position with major advancements in multimodal imaging, machine learning-based data integration, portable sampling devices, and clinical validation studies that are pushing the field towards precision treatment. Full article

Background/Objective: Biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer indicates disease progression. Although type 2 diabetes mellitus (T2D) shows a paradoxical association with prostate cancer risk, the prognostic role of T2D-related genetic variants remains unclear. Methods: We analyzed 113 common T2D susceptibility-related single-nucleotide polymorphisms (SNPs) in 644 Taiwanese men with localized prostate cancer (D’Amico risk classification: 12% low, 34% intermediate, and 54% high) treated with RP. Associations between SNPs and BCR were assessed using Cox regression, adjusting for key clinicopathological factors. Functional annotation was performed using HaploReg and FIVEx, while The Cancer Genome Atlas transcriptomic data were analyzed for C2 calcium-dependent domain-containing 4A (C2CD4A) expression. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to explore related biological pathways. Results: C2CD4A SNP rs4502156 was independently associated with a reduced risk of BCR (hazard ratio = 0.80, p = 0.035). The protective C allele correlated with higher C2CD4A expression. Low C2CD4A expression is associated with advanced pathological stages, higher Gleason scores, and disease progression. GSEA revealed negative enrichment of mitotic and chromatid segregation pathways in high-C2CD4A-expressing tumors, with E2F targets being the most suppressed. GSVA confirmed an inverse correlation between C2CD4A expression and E2F pathway activity, with CDKN2C as a co-expressed functional gene. Conclusions: The T2D-related variant rs4502156 in C2CD4A independently predicts a lower risk of BCR, potentially via suppression of the E2F pathway, and may serve as a germline biomarker for postoperative risk stratification. Full article

Background/Objectives: The purpose of this study was to investigate the association between HER-2 expression and clinicopathological characteristics, biochemical recurrence (BCR) rate, and BCR-free survival in localized prostate cancer (PCa) patients after radical prostatectomy (RP). Methods: Between January 2018 and December 2019, 44 patients with pathologically confirmed localized PCa who underwent RP were included in this study. According to the expressed level of HER-2 protein, patients were divided into four cohorts: cohort-1 (HER-2 0), cohort-2 (HER-2 1+ or 2+), cohort-3 (HER-2 0 or 1+), and cohort-4 (HER-2 2+); the clinicopathological and clinical outcomes were analyzed and compared between cohort-1 and cohort-2, and cohort-3 and cohort-4, respectively. Univariable and multivariable COX regression models and Kaplan–Meier curves were used to determine the association between HER-2 expression and clinicopathological outcomes, including Gleason score (GS), pathological T (pT) stage, positive surgical margins (PSM), and BCR-free survival, respectively. Results: The median follow-up time was 43 months (IQR 35–49). Among the 44 patients, 20 (45.5%) exhibited HER-2 immuno-reactivity, including 14 (31.8%) with HER-2 1+, 6 (13.64%) with HER-2 2+, and 0 (0%) with HER-2 3+ staining. The proportion of patients with PSM was significantly lower in the HER-2 0 group than in those with HER-2 1+ or 2+ (25.0% vs. 65.0%, p = 0.008). Multivariable logistics regression models revealed that HER-2 1+ or 2+ was an independent risk factor that was strongly associated with a higher proportion of PSM (OR, 2.69; 95% CI, 0.62–11.71, p = 0.042). A total of 18 (40.9%) patients experienced BCR after surgery, including 6 (25%) in cohort-1 and 12 (60.0%) in cohort-2 (p = 0.019), as well as 13 (34.2%) in cohort-3 and 5 (83.3%) in cohort-4 (p = 0.023). Kaplan–Meier analysis showed that patients in cohort-1 (HER-2 0) had significantly longer BCR-free survival than those in cohort-2 (HER-2 1+ or 2+) (p < 0.001), and those in cohort-3 had longer BCR-free survival than those in cohort-4 (p < 0.001). Furthermore, patients with PSM showed significantly shorter BCR-free survival compared to those with patients with negative surgical margins (NSM) (p = 0.005). Multivariable Cox regression analysis revealed that HER-2 1+, 2+ (HR, 17.00; 95% CI, 1.38–210.22, p < 0.001), HER-2 2+ (HR, 2.85; 95% CI, 1.23–3.25, p = 0.004), and PSM (HR, 6.12; 95% CI, 3.08–11.72, p = 0.007) were all significant independent predictors of BCR following surgery. Conclusions: HER-2 expression is a common phenomenon in PCa; nearly half of the proportion of localized PCa had HER-2 1+ or 2+, but the cases that expressed HER-2 3+ were rare. Cases with HER-2 1+ or 2+ were more likely to develop BCR compared with HER-2 0. The HER-2 1+ or 2+ expression was closely associated with a higher incidence of PSM and was an independent predictor of shorter BCR-free survival in patients with localized prostate cancer after radical prostatectomy. Full article

Background & Objectives: Current guidelines recognize a subgroup of favorable intermediate-risk (FIR) ISUP grade group (GG) 2 prostate cancer (PCa) that may be eligible for active surveillance (AS). However, upgrading and upstaging to more aggressive disease are frequently observed. We aimed to identify risk factors for adverse pathology in this cohort to better define clinical scenarios where AS may need to be reconsidered. Methods: We retrospectively analyzed 170 patients diagnosed with ISUP GG2 PCa by multiparametric MRI (mpMRI)/TRUS fusion biopsy, all treated with radical prostatectomy (RP). Patients with FIR disease were evaluated for upstaging to ≥pT3 or upgrading to ISUP GG of ≥3 at RP. Multivariable logistic regression identified predictors of adverse pathology. Key Findings and Limitations: Among 170 FIR patients, median PSA was 5.6 ng/mL. Most had PI-RADS 4 (57%) or 5 (20%) lesions; 13% were diagnosed by systematic biopsy only. At RP, 28% showed adverse pathology, including 5 patients (2.9%) with lymph node metastases. Independent predictors were a PI-RADS Score of ≥4, PSA of >7 ng/mL, and clinical T-stage on digital rectal examination. Conclusions and Clinical Implications: Nearly 1/3 of FIR PCa patients were upstaged to high-risk PCa at RP. Based on these findings, AS in clinical practice should only be considered after thorough patient counseling and performed using a stringent follow-up and staging regimen to minimize the risk of further disease progression. A key limitation is the lack of the percentage of Gleason pattern 4. Full article