Gleason Score Research Articles

Prostate-specific antigen, digital rectal examination, and prostate cancer detection: A study based on more than 7000 transrectal ultrasound-guided prostate biopsies in Ghana

Purpose of the studyThis study aims to determine the role of serum prostate-specific antigen (PSA) levels and digital rectal examination (DRE) in predicting the histological outcomes of prostate biopsies by analyzing a database of over 7000 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies. MethodsWe conducted a retrospective analysis of men who underwent TRUS-guided prostate biopsies at Korle Bu Teaching Hospital, a tertiary referral center in Accra, Ghana, from July 2005 to December 2022. The biopsies, which included 10 to 12 core samples, were prompted by PSA levels greater than 4.0 ng/mL, abnormal DRE findings, or both. We then correlated histopathology results with PSA and DRE findings. ResultsOut of 7,338 patients who presented for biopsy, 76.3% were between the ages of 60 and 79. Histology reports were available for 5,289 patients, of whom 2,564 (48.5%) were diagnosed with prostate cancer. Cancer detection rates based on PSA levels were as follows: 21.6% for PSA <4 ng/mL, 21.7% for PSA 4-10 ng/mL, 32.7% for PSA 10-20 ng/mL, 53.0% for PSA 20-50 ng/mL, 71.5% for PSA 50-100 ng/mL, and 92.0% for PSA >100 ng/mL. When DRE findings were classified according to the 2016 TNM System (AJCC 8th Edition) as T1, T2, T3, and T4, cancer detection rates were 26.8%, 51.8%, 87.6%, and 95.7%, respectively. The overall cancer detection rate was significantly higher with abnormal DRE findings (64.6% vs. 26.7%, p < 0.001). Additionally, 78.2% of the detected cancers were high-grade (Gleason score of 7 or more). ConclusionThis extensive study of Ghanaian men undergoing TRUS biopsies reveals a high prostate cancer detection rate, with nearly 80% of the detected cancers being high-grade. These findings underscore the importance of PSA and DRE in the early detection of prostate cancer and should be considered in patient counseling and discussions regarding the implementation of prostate cancer screening programs in this population.

Role of Apparent Diffusion Coefficient Value and Apparent Diffusion Coefficient Ratio as Prognostic Factors for Prostate Cancer Aggressiveness

Background: Prostate cancer is one of the most prevalent cancers in the male population. To determine the aggressiveness of suspected lesions precisely, predictive models are increasingly being developed using quantitative MRI measurements, and particularly the ADC value. This study aimed to determine whether ADC values could be used to establish the aggressiveness of prostate cancer. Methods: A retrospective single-center study included 398 patients with prostate cancer who underwent a multiparametric MRI prior to radical prostatectomy. DWI ADC values were measured (µm2/s) using b values of 50 and 1000. The dominant lesion best visualized on MRI was analyzed. The ADC values of the index lesion and reference tissue were compared to tumor aggressivity according to the Gleason grade groups based on radical prostatectomy results. Statistical analysis was performed using the Mann–Whitney U test, Kruskal–Wallis H test, Spearman’s rank correlation, and ROC curves. Results: A very strong negative correlation (rs = −0.846, p &lt; 0.001) between ADC and GS was found. ROC analysis revealed an AUC of 0.958 and an ADC threshold value of 758 µm2/s in clinically significant prostate cancer diagnoses using the absolute ADC value, with no advantage of using the ADC ratio over the absolute ADC value being identified. Conclusion: DWI ADC values and the calculated ADC ratio have a significant inverse correlation with GS. The findings indicate a strong capability in determining prostate cancer aggressiveness, as well as the possibility of assisting with assigning PI-RADS categories using ADC as quantitative metrics.

G-Protein-Coupled Receptor-Associated Sorting Protein 1 Overexpression Is Involved in the Progression of Benign Prostatic Hyperplasia, Early-Stage Prostatic Malignant Diseases, and Prostate Cancer

Background/Objectives: Prostate cancer (PCa) is a prevalent malignancy, necessitating accurate diagnostic methods to distinguish it from benign conditions such as benign prostatic hyperplasia (BPH). Current diagnostic tools, relying primarily on serum prostate-specific antigen (PSA) levels, lack specificity, leading to an over-diagnosis and unnecessary treatment of patients with benign conditions. This study explores G-protein-coupled receptor-associated sorting protein 1 (GASP-1) as a more sensitive biomarker for PCa detection. Methods: Prostate tissue microarrays of healthy, BPH, and prostate cancer patients with different Gleason scores were studied. Polyclonal antibodies targeted against GASP-1 were used for routine immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) analyses. Results: The results indicated a 5-fold difference in serum GASP-1 levels between BPH and PCa, which was validated through GASP-1 IHC. Furthermore, a novel scoring system, the H-score, assesses GASP-1 granules’ intensity and size, revealing a clear distinction between BPH and PCa. An additional analysis of GASP-1 expression between PCa cases with different Gleason scores reveals that GASP-1 overexpression correlates with PCa severity, providing insights into disease progression. Conclusions: The study supports GASP-1′s role as a promising diagnostic marker, supplementing PSA testing, and offering improved risk stratification for PCa. Additionally, an open-source software system is introduced for an efficient GASP-1 granule color analysis, enhancing diagnostic accuracy.

Factors Affecting Biochemical Recurrence After Radical Prostatectomy and Validity of CAPRA Score in Predicting Biochemical Recurrence

Objective: Biochemical recurrence (BCR) after prostate cancer (PCa) treatment is undesirable. It is important to inform a patient about BCR in preoperative evaluation. We aimed to demonstrate the effectiveness of the (The Prostate Cancer Risk Assessment) CAPRA score used to predict this situation in our study. Material and Methods: The study included 348 patients who underwent Radical Prostatectony (RP) for localized PCa. Demographic, preoperative and postoperative data were collected. CAPRA score based on preoperative total PSA value, Gleason Score, clinical T stage, percentage of positive biopsy cores and age was calculated using these data. BCR was defined as a total PSA value &gt;0.2 ng/dL for two consecutive times after RP. Follow-up periods, recurrence status and time of recurrence were recorded. Results: BCR positivity was detected in 60 (17.2%) of 348 patients. In univariate analyses, PSA level, lesion volume on MRI, ISUP grade, D’Amico risk classification, Seminal vesicule invasion (SVI) and CAPRA score were statistically significant in the groups. In multivariate analyses, PSA level, Neutrophile Lymphocyte Ratio, lesion dimension, intermediate risk according to D’amico classification, Extraprostatic extension (EPE) showed differences between both groups. The probability of biochemical progression-free in CAPRA risk groups shows a significant decrease in the probability of biochemical progression-free in the long term as risk increases in CAPRA risk groups: 91.4% in the low-risk group, 77.8% in the intermediate-risk group and only 61.7% in the high-risk group at 80-month follow-up. Conclusion: CAPRA scoring system should be supported by MpMRI findings and a new nomogram should be developed with these findings.

Oncological Outcomes of Partial Gland Ablation Using High-Intensity Focused Ultrasound After Additional Confirmatory Transperineal Mapping Biopsy in Men with Prostate Cancer

Background/Objectives: To evaluate whether additional confirmatory transperineal mapping biopsy (TPMB) in men with localized prostate cancer (PCa) alters the treatment plan and outcome of partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU). Methods: We retrospectively reviewed data from 96 patients who underwent PGA using HIFU between January 2020 and June 2022. After multiparametric magnetic resonance imaging (mpMRI), all men underwent transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy and systematic biopsy. Men eligible for PGA using HIFU first underwent confirmatory TPMB. Any changes in the treatment plan after TPMB were analyzed. Follow-up TRUS-guided biopsy was performed 1 year post-operatively to evaluate oncological outcomes. Clinically significant PCa (csPCa) was defined as Gleason grade (GG) ≥ 2. Results: Among all subjects, the median age (IQR) was 65.0 (60.0–72.0) years and the prostate-specific antigen level was 5.20 (3.71–7.81) ng/mL. The results of both TRUS-guided biopsy and TPMB led to a change in the treatment plan (from unilateral to bilateral PGA) for 13 (13.5%) patients. The 1-year follow-up TRUS-guided biopsy identified PCa in 13 (13.5%) patients, and csPCa in 7 (7.3%) patients. The infield- and outfield-positive rates were 8.3% (8/96) and 3.1% (3/96), respectively, for any PCa, and 3.1% (3/96) and 2.1% (2/96), respectively, for csPCa. Conclusions: Confirmatory TPMB results in better disease identification and localization, thereby affecting the treatment plan and improving oncological outcomes. Therefore, confirmatory TPMB should be considered to establish an appropriate strategy for patients with localized PCa eligible for PGA using HIFU.

Targeted microwave ablation of localised prostate cancer: Initial results of VIOLETTE trial

AbstractObjectiveThe aim of this study was to assess the precision and safety of targeted microwave ablation (TMA) using organ‐based tracking (OBT) fusion, in patients with intermediate risk prostate cancer.Patients and methodWe conducted a prospective, multicentric trial. Eligible patients had a prostate‐specific antigen (PSA) &lt; 20 ng/mL, a magnetic resonance imaging (MRI)‐visible index tumour of Gleason score 3 + 4, with largest axis ≤15 mm and distant of at least 5 mm from the rectum and apex. TMA was performed with microwave needle applicator using OBT fusion, with a transperineal or a transrectal approach. In this interim analysis, we evaluated precision, safety, urinary and sexual outcomes, and PSA density kinetics.ResultsAt this point, 37 patients were treated in five centres. Median (interquartile range) age is 68 (63–72) years. Baseline median prostate volume and PSA are of 45 (34–57) mL and 8 (6.2–10.8) ng/mL, respectively. Median largest tumour axis on T2W MRI is of 11 mm (10–13). Patients were treated under general anaesthesia or conscious IV sedation in an outpatient setting. Anaesthesia had a median duration of 78 (66–90) min. A median number of 3 (2–4) 12‐W ablations of 2 to 5 min were performed per patient. After a median follow‐up of 6 (2.4–10) months, we observed 58 adverse events (AE) in 22 patients. These were of Common Terminology Criteria for Adverse Events (CTCAE) grade 1, 2 and 3 in 43 (74%), 13 (22%) and 2 (4%) cases. Six (15%) patients had an acute urinary retention, five of which considered as severe AE because of rehospitalisation. We did not observe any significant difference in International Prostate Symptom Score (IPSS), Male Sexual Health Questionnaire‐ejaculatory dysfunction (MSHQ‐EjD) and International Index of Erectile Function (IIEF5) from baseline to last follow‐up. Median PSA density evolved from 0.2 (0.1–0.3) at baseline to 0.1 (0.07–0.16) at 12 months.ConclusionsThese preliminary results suggest that TMA using OBT fusion is precise and safe in patients with intermediate risk localised prostate cancer. Further inclusions and follow‐up are needed to assess oncological outcome.

The Association Between Lymphovascular or Perineural Invasion in Radical Prostatectomy Specimen and Biochemical Recurrence

Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR). Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan–Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion. Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion (p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion (p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01–2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13–2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular (p = 0.740) or perineural invasion (p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion. Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR.

Overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities

Abstract Background Evidence regarding the likelihood of overdiagnosis in prostate cancer (CaP) screening with PSA are mainly based on clinical trials, which include younger population with fewer comorbidities than those receiving the test in clinical practice. We aimed to assess the likelihood of overdiagnosis and associated variables using real-world data. Methods Retrospective cohort of men &amp;gt;40 years with PCa, who had been diagnosed being asymptomatic and after a positive PSA test in the previous 12 months in two hospitals (2004-2022). The probability of overdiagnosis was estimated considering the life expectancy of the Spanish male in the year 2022 and the Charlson Comorbidity Index (lead time 10 years). PSA values and Gleason score were included as independent variables. Results Of the 2,331 patients in the cohort, 1,070 (46%) met the inclusion criteria for this analysis. The median follow-up time was 5.7 years (IQR 3.2-8.6). The median age was 71 years (IQR 65-78) and 37% had more than one comorbidity. At diagnosis, the median life expectancy was 12 years (IQR 4-18) and the probability of overdiagnosis was 30.8% (IQR 17.6-52.4). Patients with PSA levels &amp;gt;10 mg/dl tended to be older and with more comorbidities than those with PSA levels 4-10 mg/dl, and thus, with shorter life expectancy. The median probability of overdiagnosis was higher in patients with PSA levels &amp;gt;10 mg/dl (41.4%, IQR 21.5-73.9) than in those with PSA levels 4-10 mg/dl (20.1%, IQR 12.8-30.4), p &amp;lt; 0.001. Correspondingly, patients with Gleason score ≥8 were more likely to be overdiagnosed (median 42.6%, IQR 23.6-68.6) than those with Gleason score ≤6 (median 20.1%, IQR 12.8-30.4) (p &amp;lt; 0.001). Conclusions In clinical practice, older patients with comorbidities showed high PSA levels and Gleason score ≥8, presenting low life expectancy at diagnosis and, therefore, high probability of overdiagnosis. This highlights the importance of considering the patient’s comorbidities when ordering a new PSA test. Key messages • A detailed assessment of the prevalence of comorbidities among CaP patients in real-life settings has significant implications for patient management. • The decision to make an early diagnosis should be based on individual life expectancy, where comorbidity is at least as important as age.

Predicting time to castration resistance with androgen-receptor signaling inhibitors in hormone-sensitive prostate cancer: data from ULTRA-Japan Consortium.

Androgen-receptor signaling inhibitors (ARSIs) become the new standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). It is unknown whether time to castration resistance (TTCR), when using the first-line ARSIs, offers predictive value in mHSPC. We sought to assess the clinical outcomes for mHSPC patients treated with first-line ARSIs focusing on the TTCR. Data from the ULTRA-Japan study cohort from five academic institutes (496 mHSPC patients) were retrospectively analyzed. The median overall survival (OS) in the total cohort was 80months with a median follow-up of 18months. Of 496 patients, 332 (67%), 82 (16.5%), and 82 (16.5%) were treated with first-line abiraterone acetate + prednisone, enzalutamide, and apalutamide, respectively. During the follow-up, a total of 155 (31%) were diagnosed with mCRPC with a median TTCR of 10months. In those 155 patients, TTCR > 12months is an independent predictor of longer OS from the first-line ARSIs. Cox regression analysis of the TTCR from initiating first-line ARSI in 496 mHSPC patients revealed three variables as independent predictors of shorter TTCR, including Gleason's score (GS) ≥ 9, the extent of disease (EOD) ≥ 2, and the presence of liver metastasis. Our results indicate that mHSPC patients with those three features are likely to have primary resistance to first-line ARSIs (doublet therapy), thus requiring consideration of other options, such as the recent triplet approach.

Machine learning discrimination of Gleason scores below GG3 and above GG4 for HSPC patients diagnosis

This study aims to develop machine learning (ML)-assisted models for analyzing datasets related to Gleason scores in prostate cancer, conducting statistical analyses on the datasets, and identifying meaningful features. We retrospectively collected data from 717 hormone-sensitive prostate cancer (HSPC) patients at Yunnan Cancer Hospital. Of these, data from 526 patients were used for modeling. Seven auxiliary models were established using Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT), Extreme gradient boosting tree (XGBoost), Adaptive Boosting (Adaboost), and artificial neural network (ANN) based on 21 clinical biochemical indicators and features. Evaluation metrics included accuracy (ACC), precision (PRE), specificity (SPE), sensitivity (SEN) or regression rate(Recall), and f1 score. Evaluation metrics for the models primarily included ACC, PRE, SPE, SEN or Recall, f1 score, and area under the curve(AUC). Evaluation metrics were visualized using confusion matrices and ROC curves. Among the ensemble learning methods, RF, XGBoost, and Adaboost performed the best. RF achieved a training dataset score of 0.769 (95% CI: 0.759—0.835) and a testing dataset score of 0.755 (95% CI: 0.660—0.760) (AUC: 0.786, 95%CI: 0.722—0.803), while XGBoost achieved a training dataset score of 0.755 (95% CI: 95%CI: 0.711—0.809) and a testing dataset score of 0.745 (95% CI: 0.660—0.764) (AUC: 0.777, 95% CI: 0.726—0.798). Adaboost scored 0.789 on the training dataset (95% CI: 0.782—0.857) and 0.774 on the testing dataset (95% CI: 0.651—0.774) (AUC: 0.799, 95% CI: 0.703—0.802). In terms of feature importance (FI) in ensemble learning, Bone metastases at first visit, prostatic volume, age, and T1-T2 have significant proportions in RF’s FI. fPSA, TPSA, and tumor burden have significant proportions in Adaboost’s FI, while f/TPSA, LDH, and testosterone have the highest proportions in XGBoost. Our findings indicate that ensemble learning methods demonstrate good performance in classifying HSPC patient data, with TNM staging and fPSA being important classification indicators. These discoveries provide valuable references for distinguishing different Gleason scores, facilitating more accurate patient assessments and personalized treatment plans.

Triple-console robotic telesurgery: first impressions and future impact.

Telesurgery has been recently gaining momentum as a natural evolution of robotic surgery. Besides providing expert surgical care to patients who cannot geographically access it, telesurgery can also facilitate surgical collaboration between surgeons who might need urgent assistance or coaching experts. The idea of having two consoles, with one remote and one local, has been the ideal setup for such ecosystems. However collaborations can take on many forms and might require more than one remote surgeon, depending on procedure complexity and surgeon availability. The objective of the study was to describe our perspectives and experience performing telesurgery on one patient, using three surgeon consoles for three surgeons, operating from three separate cities. In November 2023, a triple-console, robot-assisted radical prostatectomy (RARP) was performed in a collaborative effort among three surgeons in three separate locations employing telesurgery using the Kangduo Endosopic Surgical Robot (KD-SR-01, Sagebot Medical). The furthest distance between participants was approximately 2600km between Beijing and Hainan. We described and illustrated the applications and outcomes of this procedure to treat a single patient with prostate cancer. The local surgeon, along with the operating room team, and the patient were in Hainan, while the other two surgeons were in Beijing and Hunan Telesurgery command centers. The procedure lasted approximately 120min and there were no intra- or postoperative complications. Estimated blood loss was 100ml. The patient was ambulating 4h after surgery and remained in the hospital for 2days secondary to the postoperative care protocol followed by the local team taking care of the patient. The Foley catheter was removed on postoperative day 7 without complication. The final pathology was ISUP Grade Group 4 (Gleason score 4 + 4 = 8) T2cN0 with negative surgical margins. Our experience shows that telesurgery involving multiple surgeons at multiple remote locations is possible and can be completed safely with low-latency connections via available telecommunication networks.

Correlation of magnetic resonance imaging and computed tomography with biological factor expression and lymph node metastasis in aggressive prostate cancer.

This paper focused on probing the correlation of magnetic resonance imaging (MRI) and computed tomography (CT) manifestations with biological factor expression and lymph node metastasis (LNM) in aggressive prostate cancer (PCa). A total of 136 PCa patients underwent surgical treatment, and received CT and MRI examinations before surgery, whereby the apparent diffusion coefficient (ADC) values of quantitative MRI (qMRI) parameters were obtained. Patients were categorized into the non-aggressive PCa group and aggressive PCa group according to the postoperative pathological results and Gleason scores. The expression of biological factors [prostate-specific antigen (PSA), proliferating cell nuclear antigen (PCNA), p27, and ki-67] in both groups was tested. CT and MRI manifestations of aggressive PCa patients were analyzed. The qMRI parameters, biological factors levels and LNM were compared in two groups; the relationships between CT and MRI manifestations, qMRI parameters and positive expression of biological factors and LNM were probed in two groups. In the aggressive PCa group, MRI and CT presented different degrees of abnormal prostate changes. In the aggressive PCa group, PSA and p27 expression and ADC values were lower, and PCNA and ki-67, and LNM rates were higher. Patients' LNM rate was higher than that of ≤ 2 cm when the tumor diameter was &gt; 2 cm. ADC values were positively correlated with PSA and p27 positive expression, and negatively correlated with PCNA, ki-67 and LNM in the aggressive PCa group. MRI and CT manifestations of aggressive PCa had certain characteristics; MRI manifestations and qMRI possessed a correlation with biological factors and LNM; ADC could be employed to assess the aggressiveness of PCa.

Nodal radiotherapy for prostate adenocarcinoma recurrence: predictive factors for efficacy

BackgroundNodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes.Materials and methodsThis retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event–biochemical or imaging recurrence, or death.ResultsA total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p &amp;lt; 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time &amp;gt;6 months, and a Gleason score &amp;lt;8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications.DiscussionFor an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients.

A case of rapidly progressive prostate cancer with bone and lymph node metastasis after contact laser vaporization for benign prostatic hyperplasia

IntroductionProstate cancer is incidentally diagnosed in 6%–11% of benign prostatic hyperplasia surgeries.Case presentationA 79‐year‐old man was diagnosed with benign prostatic hyperplasia. The prostate volume was 54.5 mL, and the prostate‐specific antigen level was 7.121 ng/mL. Magnetic resonance imaging and prostate biopsy were not performed. He then underwent contact laser vaporization of the prostate. After 3 months, gross hematuria occurred, and the prostate‐specific antigen level was 62.495 ng/mL. Cystoscopy and magnetic resonance imaging revealed prostate cancer with bladder invasion. Prostate biopsy and transurethral resection were performed, revealing adenocarcinoma with a Gleason score of 5 + 5. The patient was diagnosed with prostate cancer T4N1M1b, and triplet therapy was initiated. After 6 months, the prostate‐specific antigen level was 0.037 ng/mL, and the metastases had shrunk.ConclusionVaporization for high‐grade prostate cancer can lead to rapid progression. Therefore, screening for prostate cancer before benign prostatic hyperplasia surgery is important.

Impact of Obesity on Gleason Score- Elderly and Very Elderly Patients with Prostate Cancer Indicated for Radical Radiotherapy

Introduction: Prostate cancer is an important public health concern in Brazil, especially among older men, with a significant mortality rate. In addition to advanced age, obesity emerges as a relevant risk factor, associated with a worse prognosis of the disease. Objective: To investigate the relationship between body mass index (BMI) and Gleason score in older and very older patients with prostate cancer indicated for radiotherapy treatment. Methods: Prospective, descriptive, and longitudinal study with 258 patients with prostate cancer, evaluating age, initial PSA, BMI, race, and Gleason Score. Result: Findings revealed an association between a higher BMI and a more aggressive degree of disease, as indicated by higher Gleason scores. Conclusion: Overweight and obese patients have a higher and more evident Gleason score in older patients compared to the very older, being more notable in the older. This study is one of the few studies to examine the link between BMI and poor prognosis in prostate cancer patients

Low SMARCD3 expression is associated with poor prognosis in patients with prostate cancer.

SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.

Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in a cross-sectional study

Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.

4D pathology: translating dynamic epithelial tubulogenesis to prostate cancer pathology.

The Gleason score is the gold standard for grading of prostate cancer (PCa) and is assessed by assigning specific grades to different microscopical growth patterns. Aside from the Gleason grades, individual growth patterns such as cribriform architecture were recently shown to have independent prognostic value for disease outcome. PCa grading is performed on static tissue samples collected at one point in time, whereas in vivo epithelial tumour structures are dynamically invading, branching and expanding into the surrounding stroma. Due to the lack of models that are able to track human PCa microscopical developments over time, our understanding of underlying tissue dynamics is sparse. We postulate that human PCa expansion utilizes embryonic and developmental tubulogenetic pathways. The aim of this study is to provide a comprehensive overview of developmental pathways of normal epithelial tubule formation, elongation, and branching, and relate those to the static microscopical PCa growth patterns observed in daily clinical practise. This study could provide a rationale for the discerned pathological interobserver variability and the clinical outcome differences between PCa growth patterns.

Prognostic Significance of Cribriform Architecture of Pattern 4 Prostatic Adenocarcinomas

Objective: Among prostate cancer patients, the Gleason score is associated with adverse clinical outcomes. We aimed to determine whether cribriform architecture in prostate cancer patients without a history of treatment was related to prognosis in patients with Gleason pattern 4 of prostate cancer.  Material and Methods: A prospective cross-sectional study included (n=450) consecutive prostate biopsy specimens between June 2014 and May 2015, out of which (n=237) had pattern 4 prostate adenocarcinoma. Demographic, clinical, and follow-up details were obtained. Patients (n = 86) with a treatment history were excluded from the study.  Results: Univariate Cox regression analysis of diagnostic biopsies from (n=151) patients with pattern 4 of prostate cancer who had been followed for an average of 70.3 months demonstrated that the cribriform architecture of prostate cancer with pattern 4 was independently associated with poorer disease-specific survival in biopsies with a hazard ratio (HR) of 3.1, 95% Confidence Interval (CI) of 0.9-10.6, and P value of &lt;0.001.  Conclusion: It is concluded that a cribriform architecture of prostate cancer in biopsies with pattern 4 adenocarcinoma is associated with a lower disease- specific survival rate. Therefore, it is essential to report the presence and percentage of cribriform architecture in patients with pattern 4 prostate cancer.

Focal Unspecific Bone Uptake on [18F]PSMA-1007 PET: Evaluation Analog PROMISE Criteria and Validation via PET/CT Follow-Up.

Background: Focal unspecific bone uptake (UBU) is common in [18F]PSMA-1007 PET/CT, yet its clinical significance remains unclear, causing uncertainty in treatment decisions. Material and Methods: We retrospectively analyzed 99 prostate cancer patients (age 69 ± 7) who underwent [18F]PSMA-1007 PET/CT scans (3 MBq/kg; uptake time 70 ± 14 min) for staging and follow-up (after 13.0 ± 7.2 months). Semiquantitative assessment using the miPSMA score, analogous to the PROMISE criteria, evaluated the prevalence of UBU and bone metastases. Results: In the initial PET/CT scan, 56 patients had 230 lesions classified as UBU. A total of 19 patients were found to have bone metastases and UBU, while 24 patients had no focal bone uptake. UBU distribution was as follows: ribs (50%), spine (30%), pelvis (15%), and other sites (5%). There were no significant differences in age, Gleason score, injected tracer dose, uptake time, SUVpeak of UBU, or SUVmean in the spleen and parotid gland between patients with and without UBU. Follow-up showed stable miPSMA-score and CT appearance in 44/56 patients with UBU (79%), minor changes in 5/56 patients (8%), and new bone metastases in 7/56 patients (12%). Patient-specific analysis indicated at least one bone metastasis initially classified as UBU in 3/56 patients (5%) and new bone metastases in 4/56 patients (7%). In total, 4 of the 24 patients (17%) without initial focal uptake developed osseous metastases at follow-up. Conclusions: No significant differences were found between patients with or without UBU. Only a small portion of UBU (2%) evolved into metastases, a lower rate than the development of new osseous metastases, which appears to be independent of UBU.