Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations.

BACKGROUND: Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored. DESIGN: In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes). RESULTS: The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian-type clear cell phenotype, two mucinous tumours resembling low-grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post-radiation mucinous adenocarcinoma had genomic findings consistent with bi-allelic inactivation of TP53, as well as multiple copy-number changes with regional and chromosomal arm-level copy-number losses. The Müllerian-type clear cell carcinoma exhibited a complex copy-number profile with numerous regional and arm-level copy-number changes, as well as focal amplification events, including copy-number gain of 8q and amplification of a region within 20q13. Both low-grade mucinous tumours resembling LAMN harboured hot-spot gain-of-function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma. CONCLUSION: Our results suggest that primary low-grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain-of-function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.

Correlation between pre-radical prostatectomy standardized SUVmax ratios detected on 68Ga-PSMA-I&T PET/CT and final histopathology outcomes: an in-depth analysis.

OBJECTIVE: To evaluate the predictive potential of the maximum standardized uptake value(SUVmax) value of intraprostatic tumors derived from preoperative 68Ga-PSMA-I&T PET/CT (SUVT), and its ratios to SUVmax in the liver (SUVTLR) and parotid gland (SUVTPR) with respect to histopathological findings. MATERIALS AND METHODS: Data from patients who underwent radical prostatectomy (RP) for prostate cancer (PC) at our clinic between 2017 and 2020 were assessed. Patients with a secondary malignancy, a history of transurethral prostate resection, prior treatment for PC, or who received salvage RP were excluded. Whole-body images obtained using the same device, as per the guidelines, were reviewed by two nuclear medicine specialists with more than a decade of experience to reach a consensus for each lesion. The relationships between age, PSA, Prostate Volume, clinical T stage, biopsy International Society of Urological Pathology grade (ISUP), D'amico risk group, intraprostatic tumor volume (HPTV) identified in the final histopathological specimen review, HP-ISUP grade, seminal vesicle invasion (SVI), extracapsular invasion (ECI), positive surgical margine (PSM), SUVT, SUVTLR, and SUVTPR were analyzed. RESULTS: The mean age of the 64 included patients was 64.1 ±â€¯5.3. A statistically significant correlation was found between SUVT, SUVTLR, SUVTPR values, and histopathologic stage parameters, such as biopsy ISUP, D'amico Risk Classification, HP-ISUP, HPTV (p < 0.05). PSMATV, SUVT, and SUVTLR were statistically significant predictors of extracapsular invasion, while PSA, PSMATV, and SUVTLR were significant predictors of SVI (p < 0.05). CONCLUSION: The standardized SUVT, SUVTLR, and SUVTPR values could be employed as noninvasive markers to assist in predicting postoperative histopathological findings, particularly ECI, SVI, and PSM.

Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features.

BACKGROUND: Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification. METHODS: We performed whole-genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and lymph nodes of five treatment-naive patients with locally advanced disease. We spatially mapped the clonal composition of cancer across the prostate and the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes in each individual by analysing a total of > 19,000 copy number corrected single nucleotide variants. RESULTS: In each patient, we identified sample locations corresponding to the earliest part of the malignancy. In patient 10, we mapped the spread of cancer from the apex of the prostate to the seminal vesicles and identified specific genomic changes associated with the transformation of adenocarcinoma to amphicrine morphology during this spread. Furthermore, we show that the lymph node metastases in this patient arose from specific cancer clones found at the base of the prostate and the seminal vesicles. In patient 15, we observed increased mutational burden, altered mutational signatures and histological changes associated with whole genome duplication. In all patients in whom histological heterogeneity was observed (4/5), we found that the distinct morphologies were located on separate branches of their respective evolutionary trees. CONCLUSIONS: Our results link histological transformation with specific genomic alterations and phylogenetic branching. These findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes causally linked to morphological transformation. Our study demonstrates the value of integrating multi-region sequencing with histopathological data to understand tumour evolution and identify mechanisms of prostate cancer spread.

The practical clinical role of machine learning models with different algorithms in predicting prostate cancer local recurrence after radical prostatectomy.

BACKGROUND: The detection of local recurrence for prostate cancer (PCa) patients following radical prostatectomy (RP) is challenging and can influence the treatment plan. Our aim was to construct and verify machine learning models with three different algorithms based on post-operative mpMRI for predicting local recurrence of PCa after RP and explore their potential clinical value compared with the Prostate Imaging for Recurrence Reporting (PI-RR) score of expert-level radiologists. METHODS: A total of 176 patients were retrospectively enrolled and randomly divided into training (n = 123) and testing (n = 53) sets. The PI-RR assessments were performed by two expert-level radiologists with access to the operative histopathological and pre-surgical clinical results. The radiomics models to predict local recurrence were built by utilizing three different algorithms (i.e., support vector machine [SVM], linear discriminant analysis [LDA], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]). The combined model integrating radiomics features and PI-RR score was developed using the most effective classifier. The classification performances of the proposed models were assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences between the training and testing sets concerning age, prostate-specific antigen (PSA), Gleason score, T-stage, seminal vesicle invasion (SVI), perineural invasion (PNI), and positive surgical margins (PSM). The radiomics model based on LR-LASSO exhibited superior performance than other radiomics models, with an AUC of 0.858 in the testing set; the PI-RR yielded an AUC of 0.833, and there was no significant difference between the best radiomics model and the PI-RR score. The combined model achieved the best predictive performance with an AUC of 0.924, and a significant difference was observed between the combined model and PI-RR score. CONCLUSIONS: Our radiomics model is an effective tool to predict PCa local recurrence after RP. By integrating radiomics features with the PI-RR score, our combined model exhibited significantly better predictive performance of local recurrence than expert-level radiologists' PI-RR assessment.

The Role of Multiparametric MRI (mpMRI) in the Prediction of Adverse Prostate Cancer Pathology in Radical Prostatectomy Specimen.

INTRODUCTION: Prostate cancer (PCa) risk stratification is essential in guiding therapeutic decision. Multiparametric magnetic resonance tomography (mpMRI) holds promise in the prediction of adverse pathologies (AP) after prostatectomy (RP). This study aims to identify clinical and imaging markers in the prediction of adverse pathology. METHODS: Patients with PCa, diagnosed by targeted biopsy after mpMRI and undergoing RP, were included. The predictive accuracy of mpMRI for extraprostatic extension (ECE), seminal vesicle infiltration (SVI), and lymph node positivity was calculated from the final histopathology. RESULTS: 846 patients were involved. Independent risk parameters include imaging findings such as ECE (OR 3.12), SVI (OR 2.55), and PI-RADS scoring (4: OR 2.01 and 5: OR 4.34). mpMRI parameters such as ECE, SVI, and lymph node metastases showed a high prognostic accuracy (73.28% vs. 95.35% vs. 93.38%) with moderate sensitivity compared to the final histopathology. The ROC analysis of our combined scoring system (D'Amico classification, PSA density, and MRI risk factors) improves the prediction of adverse pathology (AUC: 0.73 vs. 0.69). CONCLUSION: Our study supports the use of mpMRI for comprehensive pretreatment risk assessment in PCa. Due to the high accuracy of factors like ECE, SVI, and PI-RADS scoring, utilizing mpMRI data enabled accurate prediction of unfavorable pathology after RP.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.

AIM: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Solitary fibrous tumor of the seminal vesicle.

Solitary fibrous tumors (SFTs) are mesenchymal neoplasms with variable clinical behavior depending on age, tumor site, and size, and pathologic factors such as mitoses and necrosis. Imaging features on computed tomography (CT) or magnetic resonance imaging (MRI) are not specific, and the diagnosis relies on histopathology with immunohistochemistry. SFTs arising from seminal vesicles is rare and reported in only eight earlier cases. We discuss the clinical, histopathologic and positron emission tomography (PET) imaging characteristics of a 54-year-old patient with SFT of the seminal vesicle. The patient was treated with robot-assisted seminal vesiculotomy and is doing well on follow-up at two years.

Imaging of seminal vesicles: a pictorial review.

The seminal vesicles are frequently overlooked when reviewing abdominal and pelvic imaging studies, and normal variants and pathologic conditions are often missed or misinterpreted. This is largely due to lack of familiarity with the organ, its anatomic variants, congenital abnormalities and disease conditions. This pictorial review aims to familiarize the reader with the range of normal appearances, congenital anomalies and disease entities that involve the seminal vesicles to avoid overtreatment and misdiagnoses.

The oncologic risk of magnetic resonance imaging-targeted and systematic cores in patients treated with radical prostatectomy.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRI-biopsy) detects high-Grade Group (GG) prostate cancers not identified by systematic biopsy (S-biopsy). However, questions have been raised whether cancers detected by MRI-biopsy and S-biopsy, grade-for-grade, are of equivalent oncologic risk. The authors evaluated the relative oncologic risk of GG diagnosed by S-biopsy and MRI-biopsy. METHODS: This was a retrospective analysis of all patients who had both MRI-biopsy and S-biopsy and underwent with prostatectomy (2014-2022) at Memorial Sloan Kettering Cancer Center. Three logistic regression models were used with adverse pathology as the primary outcome (primary pattern 4, any pattern 5, seminal vesicle invasion, or lymph node involvement). The first model included the presurgery prostate-specific antigen level, the number of positive and negative S-biopsy cores, S-biopsy GG, and MRI-biopsy GG. The second model excluded MRI-biopsy GG to obtain the average risk based on S-biopsy GG. The third model excluded S-biopsy GG to obtain the risk based on MRI-biopsy GG. A secondary analysis using Cox regression evaluated the 12-month risk of biochemical recurrence. RESULTS: In total, 991 patients were identified, including 359 (36%) who had adverse pathology. MRI-biopsy GG influenced oncologic risk compared with S-biopsy GG alone (p < .001). However, if grade was discordant between biopsies, then the risk was intermediate between grades. For example, the average risk of advanced pathology for patients who had GG2 and GG3 on S-biopsy was 19% and 66%, respectively, but the average risk was 47% for patients who had GG2 on S-biopsy and patients who had GG3 on MRI-biopsy. The equivalent estimates for 12-month biochemical recurrence were 5.8%, 15%, and 10%, respectively. CONCLUSIONS: The current findings cast doubt on the practice of defining risk group based on the highest GG. Because treatment algorithms depend fundamentally on GG, further research is urgently required to assess the oncologic risk of prostate tumors depending on detection technique. PLAIN LANGUAGE SUMMARY: Using magnetic resonance imaging (MRI) to help diagnose prostate cancer can help identify more high-grade cancers than using a systematic template biopsy alone. However, we do not know if high-grade cancers diagnosed with the help of an MRI are as dangerous to the patient as high-grade cancers diagnosed with a systematic biopsy. We examined all of our patients who had an MRI biopsy and a systematic biopsy and then had their prostates removed to find out if these patients had risk factors and signs of aggressive cancer (cancer that spread outside the prostate or was very high grade). We found that, if there was a difference in grade between the systematic biopsy and the MRI-targeted biopsy, the risk of aggressive cancer was between the two grades.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Seminal Vesicle Treatment for Localized Prostate Cancer Treated with External Beam Radiotherapy.

This study retrospectively reviewed data from men with localized prostate cancer treated with external beam radiotherapy (EBRT). We identified 359 men with localized prostate cancer treated with curative EBRT at the Cross Cancer Institute between 2010-2011. The volume of seminal vesicles (SVs) treated as well as dose values were extracted. These volumes were compared to gold standard contours drawn by a trained expert based on consensus European Society for Radiotherapy and Oncology (ESTRO) contouring guidelines. Patient and tumor characteristics were extracted for these patients. Memorial Sloan Kettering prostate cancer nomogram was used to assign a predicted risk of SV involvement for each patient based on baseline tumor characteristics. In patients with a predicted risk of SV involvement greater than 15% (n = 184), 86.5% (SD = 18.6) of the base of the SVs were treated with EBRT, compared to 66.7% (SD = 32.6) for patients with a predicted risk of SV involvement less than 15% (n = 175, p < 0.0001). Similarly, the mean percentage of proximal and total SV volumes treated with EBRT was 75.6% (SD = 24.4) and 68.7% (SD = 26.0) for patients with a predicted risk of SV involvement of greater than 15%, compared to 50.3% (SD = 31.0, p < 0.0001) and 41.0% (SD = 27.8, p < 0.0001) for patients with a risk of less than 15%. The results indicate that all parts of the SVs are more likely to be contoured in men with >15% risk of SV involvement than those with <15% risk. However, radiation oncologists still contour a high percentage of SVs in men with <15% risk of SV involvement, suggesting that there may be over-treatment of SVs that increases the risk of rectal or bladder toxicity.

Comparison of MRI-Based Staging and Pathologic Staging for Predicting Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy.

BACKGROUND. Currently most clinical models for predicting biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) incorporate staging information from RP specimens, creating a gap in preoperative risk assessment. OBJECTIVE. The purpose of our study was to compare the utility of presurgical staging information from MRI and postsurgical staging information from RP pathology in predicting BCR in patients with PCa. METHODS. This retrospective study included 604 patients (median age, 60 years) with PCa who underwent prostate MRI before RP from June 2007 to December 2018. A single genitourinary radiologist assessed MRI examinations for extraprostatic extension (EPE) and seminal vesicle invasion (SVI) during clinical interpretations. The utility of EPE and SVI on MRI and RP pathology for BCR prediction was assessed through Kaplan-Meier and Cox proportional hazards analyses. Established clinical BCR prediction models, including the University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF-CAPRA) model and the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) model, were evaluated in a subset of 374 patients with available Gleason grade groups from biopsy and RP pathology; two CAPRA-MRI models (CAPRA-S model with modifications to replace RP pathologic staging features with MRI staging features) were also assessed. RESULTS. Univariable predictors of BCR included EPE on MRI (HR = 3.6), SVI on MRI (HR = 4.4), EPE on RP pathology (HR = 5.0), and SVI on RP pathology (HR = 4.6) (all p < .001). Three-year BCR-free survival (RFS) rates for patients without versus with EPE were 84% versus 59% for MRI and 89% versus 58% for RP pathology, and 3-year RFS rates for patients without versus with SVI were 82% versus 50% for MRI and 83% versus 54% for RP histology (all p < .001). For patients with T3 disease on RP pathology, 3-year RFS rates were 67% and 41% for patients without and with T3 disease on MRI. AUCs of CAPRA models, including CAPRA-MRI models, ranged from 0.743 to 0.778. AUCs were not significantly different between CAPRA-S and CAPRA-MRI models (p > .05). RFS rates were significantly different between low- and intermediate-risk groups for only CAPRA-MRI models (80% vs 51% and 74% vs 44%; both p < .001). CONCLUSION. Presurgical MRI-based staging features perform comparably to postsurgical pathologic staging features for predicting BCR. CLINICAL IMPACT. MRI staging can preoperatively identify patients at high BCR risk, helping to inform early clinical decision-making. TRIAL REGISTRATION. ClinicalTrials.gov NCT00026884 and NCT02594202.

Prognostic impact of palpable prostate tumors on disease progression after robot-assisted radical prostatectomy: a single-center experience.

OBJECTIVE: This study aimed to evaluate the impact of palpable prostate tumors on digital rectal exam (DRE) on the disease progression of prostate cancer (PCa) treated with RARP surgery in a tertiary referral center. MATERIALS AND METHODS: Overall, 901 patients were evaluated in a period ranging from January 2013 to October 2020. In the surgical specimen, unfavorable pathology included ISUP grade group ≥3, seminal vesicle invasion (SVI), and pelvic lymph node invasion (PLNI). Disease progression was defined as the occurrence of biochemical recurrence and/or local recurrence and/or distant metastases; its association with the primary endpoint was evaluated by Cox's proportional model. RESULTS: Palpable prostate tumors were detected in 359 (39.8%) patients. The overall median (IQR) follow-up was 40 months (17-59). PCa progressed in 159 cases (17.6%). Nodularity or induration of the prostate at DRE was significantly associated with features of unfavorable pathology, increased risk of PCa progression (hazard ratio, HR = 1.902; 95% CI: 1.389-2.605; p < 0.0001) and, on multivariable analysis, was an independent prognostic factor for disease progression after adjusting for clinical and pathological variables. CONCLUSIONS: Prostate tumors presenting with an abnormal DRE finding have an independent adverse outcome for disease progression after PCa surgery. They provide also independent prognostic information, as they may be more aggressive than impalpable PCa.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.

Tumor localization by Prostate Imaging and Reporting and Data System (PI-RADS) version 2.1 predicts prognosis of prostate cancer after radical prostatectomy.

An improved reading agreement rate has been reported in version 2.1 (v2.1) of the Prostate Imaging and Reporting and Data System (PI-RADS) compared with earlier versions. To determine the predictive efficacy of bi-parametric MRI (bp-MRI) for biochemical recurrence (BCR), our study assessed PI-RADS v2.1 score and tumor location in Japanese prostate cancer patients who underwent radical prostatectomy. Retrospective analysis was performed on the clinical data of 299 patients who underwent radical prostatectomy at Chiba University Hospital between 2006 and 2018. The median prostate-specific antigen (PSA) level before surgery was 7.6 ng/mL. Preoperative PI-RADS v2.1 categories were 1-2, 3, 4, and 5 in 35, 56, 138, and 70 patients, respectively. Tumor location on preoperative MRI was 107 in the transition zone (TZ) and 192 in the peripheral zone (PZ). BCR-free survival was significantly shorter in the PZ group (p = 0.001). In the total prostatectomy specimens, preoperative PI-RADS category 5, radiological tumor location, pathological seminal vesicle invasion, and Grade Group ≥ 3 were independent prognostic factors of BCR. These four risk factors have significant potential to stratify patients and predict prognosis. Radiological tumor location and PI-RADS v2.1 category using bp-MRI may enable prediction of BCR following radical prostatectomy.

The pathway of isolated seminal vesicle invasion has a different impact on biochemical recurrence after radical prostatectomy and pelvic lymphadenectomy.

OBJECTIVE: Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy. METHODS AND MATERIALS: We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test. RESULTS: Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172-29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months. CONCLUSIONS: Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns.

Adverse risk factors for salvage radiotherapy outcomes after radical prostatectomy in prostate cancer patients.

PURPOSE: To investigate salvage treatment approaches and treatment outcomes in high-risk prostate cancer after radical prostatectomy (RP). METHODS: In this retrospective, multicenter study, 272 patients who underwent salvage radiotherapy (RT) ± androgen deprivation therapy (ADT) for recurrent prostate cancer after RP between 2007 and 2021 were analysed. Univariate analyses of time to biochemical and clinical relapse after salvage therapies were conducted using Kaplan-Meier plots and log-rank tests. Multivariate analyses were performed using a Cox proportional hazards model to determine the risk factors for disease relapse. RESULTS: Median age was 65 (48-82) years. All patients underwent salvage prostate bed RT. Pelvic lymphatic RT was performed in 66 patients (24.3%) and ADT was included in 158 (58.1%) patients. The median PSA value before RT was 0.35 ng/mL. The median follow-up time was 64 (12-180) months. 5-years bRFS, cRFS, and OS were 75.1%, 84.8%, and 94.9% respectively. In multivariate cox regression analysis; seminal vesicle invasion (HR 8.64, 95% CI 3.47-21.48, p < 0.001), pre-RT PSA higher than 0.14 ng/mL (HR 3.79, 95% CI 1.47-9.78, p = 0.006), and ≥ 2 positive pelvic lymph nodes (HR 2.50, 95% CI 1.11-5.62, p = 0.027) were found to be unfavorable prognostic factors for bRFS. CONCLUSION: Salvage RT ± ADT provided 5-years biochemical disease control in 75.1% of patients. Seminal vesicle invasion, ≥ 2 positive pelvic nodes and delayed administration of salvage RT (PSA levels higher than 0.14 ng/mL) were found to be adverse risk factors for relapse. Such factors should be taken into account during the decision process on salvage treatment.

Senescent Tumor Cells Are Frequently Present at the Invasion Front: Implications for Improving Disease Control in Patients with Locally Advanced Prostate Cancer.

INTRODUCTION: Local tumor invasion is a critical factor for the outcome of men with prostate cancer. In particular, seminal vesicle invasion (SVI) has been reported to be associated with a more unfavorable prognosis. A better understanding of the functional state of invading prostate cancer cells is crucial to develop novel therapeutic strategies for patients with locally advanced disease. METHODS: The prognostic impact of local tumor progression was ascertained in over 1,000 men with prostate cancer. Prostate cancer specimens were stained by double-immunohistochemistry for the proliferation marker Ki-67 and the senescence marker p16INK4A. The migratory properties of senescent prostate cancer cells were analyzed in vitro using a wound healing assay and immunofluorescence microscopy for p16INK4A. RESULTS: We confirm the notion that patients with SVI have a more unfavorable prognosis than patients with extraprostatic extension alone. Surprisingly, we found that the tumor invasion front frequently harbors p16INK4A-positive and Ki-67-negative, i.e., senescent, tumor cells. While the intraprostatic tumor periphery was a hotspot for both proliferation and expression of p16INK4A, the area of SVI showed less proliferative activity but was at the same time a hotspot of cells with increased nuclear p16INK4A expression. Senescence was associated with an accelerated migration of prostate cancer cells in vitro. CONCLUSION: This proof-of-concept study shows that invading prostate cancer cells frequently show signs of cellular senescence. This finding may open new avenues for neoadjuvant and adjuvant treatment concepts in men with locally advanced prostate cancer.

Radical prostatectomy findings in patients with locally aggressive Grade group 5 prostatic adenocarcinoma and negative limited or extended pelvic lymph node dissection.

Current management options for high-risk prostate cancer (PCa) patients include radical prostatectomy with lymph node dissection and other local or systemic therapeutic approaches. However, there is paucity of data in the pathology literature on the radical prostatectomy findings in patients with locally aggressive Grade group 5 PCa with negative limited or extended lymph node dissection. A search was made through our Urologic Pathology files and consults of the senior author for patients who had radical prostatectomy specimens with locally aggressive Grade group 5 PCa and limited or extended lymph node dissection from 2010 to 2022. Patients with lymph node metastasis were excluded. Clinicopathologic and follow up data were obtained. Forty-two patients were included in the study. Mean age was 64 years (range: 49-79 years). Forty-one (98 %) patients had PCa Gleason score 4 + 5 = 9 and 1 (2 %) patient had Gleason score 5 + 4 = 9. Extraprostatic extension and/or bladder neck invasion was present in 30 (71 %) patients and seminal vesicle invasion was present in 20 (48 %) patients, of which 10 (50 %) were bilateral. Extended lymph node dissection was performed in 18 patients with mean of 22 lymph nodes (range: 6-51 lymph nodes). Limited lymph node dissection was performed in 24 patients with mean of 7 lymph nodes (range: 2-25 lymph nodes). This study demonstrates that a subset of patients with very advanced/high grade PCa still benefit from radical prostatectomy/tumor debulking even in the setting of positive margins, and may not have lymph node metastasis.