Background/Objectives: The presence of seminal vesicle invasion (SVI) in prostate cancer (PCa) is associated with poorer postoperative outcomes. This study evaluates the predictive value of magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for SVI in PCa. Methods: This cohort study included consecutive robotic prostatectomy patients for PCa at three Australian tertiary referral centres between April 2016 and September 2022. MRI and PSMA PET/CT results, clinicopathological variables, including age, BMI, prostate-specific antigen (PSA), PSA density, DRE, Biopsy Gleason score, Positive biopsy cores, PIRADS v2.1 score, MRI volume and MRI lesion size were extracted. The sensitivity, specificity, and accuracy of MRI and PSMA PET/CT for predicting SVI were compared with the histopathological results by receiver operating characteristic (ROC) analysis. Subgroup univariate and multivariate analysis was performed. Results: Of the 528 patients identified, 86 had SVI on final pathology. MRI had a low sensitivity of 0.162 (95% CI: 0.088-0.261) and a high specificity of 0.963 (95% CI: 0.940-0.979). The PSMA PET/CT had a low sensitivity of 0.439 (95% CI: 0.294-0591) and a high specificity of 0.933 (95% CI: 0.849-0.969). When MRI and PSMA PET/CT were used in combination, the sensitivity and specificity improved to 0.514 (95%CI: 0.356-0.670) and 0.880 (95% CI: 0.813-0.931). The multivariate regression showed a higher biopsy Gleason score (p = 0.033), higher PSA (p < 0.001), older age (p = 0.001), and right base lesions (p = 0.003) to be predictors of SVI. Conclusions: MRI and PSMA PET/CT independently underpredicted SVI. The sensitivity and AUC improved when they were used in combination. Multiple clinicopathological factors were associated with SVI on multivariate regression and predictive models incorporating this information may improve oncological outcomes.

Cancer spread beyond the prostate, including extraprostatic extension (other than seminal vesicle or bladder invasion; EPE)/microscopic bladder neck invasion and seminal vesicle invasion (SVI) currently classified as pT3a and pT3b lesions, respectively, does not uniformly indicate poor oncologic outcomes. Accurate risk stratification of current pT3 disease is therefore required. We herein further determined the prognostic impact of these histopathologic lesions routinely assessed and reported by pathologists, particularly their combinations. We assessed consecutive 2892 patients undergoing radical prostatectomy for current pT2 (n = 1692), pT3a (n = 956), or pT3b (n = 244) disease at our institution between 2009 and 2018. Based on our preliminary findings, point(s) were given (1 point to focal EPE, microscopic bladder neck invasion, or unilateral SVI; 2 points to nonfocal/established EPE or bilateral SVI) and summed up in each case. Our cohort had 0 point (n = 1692, 58.5%; P0), 1 point (n = 243, 8.4%; P1), 2 points (n = 657, 22.7%; P2), 3 points (n = 192, 6.6%; P3), 4 points (n = 76, 2.6%; P4), and 5 points (n = 32, 1.1%; P5). Univariate analysis revealed associations of higher points with significantly worse biochemical progression-free survival, particularly when P4 and P5 were combined. In multivariable analysis (P0 as a reference), P1 (hazard ratio [HR], 1.57; P = .033), P2 (HR, 3.25; P < .001), P3 (HR, 4.01; P < .001), and P4 + P5 (HR, 5.99; P < .001) showed significance for the risk of postoperative progression. Meanwhile, Harrell C-indexes for the current pT staging, newly developed point system, and the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score were 0.727 (95% CI, 0.706-0.748), 0.751 (95% CI, 0.729-0.773), and 0.774 (95% CI, 0.755-0.794), respectively, for predicting progression. We believe our data provide a logical rationale for a novel pathologic T-staging system based on the summed points, pT1a (0 point), pT1b (1 point), pT2 (2 points), pT3a (3 points), and pT3b (4 or 5 points), which more accurately stratifies the prognosis of prostate cancer.

OBJECTIVE: Pathologic T3b (pT3b) prostate cancer, characterized by seminal vesicle invasion (SVI), exhibits variable oncological outcomes post-radical prostatectomy (RP). Identifying prognostic factors is crucial for patient-specific management. This study investigates the impact of bilateral SVI on prognosis in pT3b prostate cancer.
METHODS: We evaluated the medical records of a multi-institutional cohort of men who underwent RP for prostate cancer with SVI between 2000 and 2012. Univariate and multivariable analyses were performed using Kaplan-Meier analysis and covariate-adjusted Cox proportional hazard regression for biochemical recurrence (BCR), clinical progression (CP), and cancer-specific survival (CSS).
RESULTS: Among 770 men who underwent RP without neo-adjuvant treatment, median follow-up was 85.7 months. Patients with bilateral SVI had higher preoperative prostate-specific antigen levels and clinical T category (all p < 0.001). Extracapsular extension, tumor volume, lymph node metastasis (p < 0.001), pathologic Gleason grade group (p < 0.001), and resection margin positivity (p < 0.001) were also higher in patients with bilateral SVI. The 5-, 10-, and 15-year BCR-free survival rates were 23.9%, 11.7%, and 8.5%; CP-free survival rates were 82.8%, 62.5%, and 33.4%; and CSS rates were 96.4%, 88.1%, and 69.5%, respectively. The bilateral SVI group demonstrated significantly lower BCR-free survival rates, CP-free survival rates, and CSS rates (all p < 0.001). Bilateral SVI was independently associated with BCR (hazard ratio, 1.197; 95% confidence interval, p=0.049), CP (p=0.022), and CSS (p=0.038) in covariate-adjusted Cox regression.
CONCLUSIONS: Bilateral SVI is a robust, independent prognostic factor for poor oncological outcomes in pT3b prostate cancer.

UNASSIGNED: The aim of the study was to investigate the predictive value of the nutritional risk index (NRI) for extracapsular extension (ECE) and seminal vesicle invasion (SVI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), and further develop and validate predictive nomograms for ECE and SVI based on the NRI.
UNASSIGNED: We retrospectively analyzed 734 PCa patients who underwent RP between 2010 and 2020 in the Department of Urology at Peking University Third Hospital. The enrolled patients were randomly divided into a primary cohort (n = 489) and a validation cohort (n = 245) in a 2:1 manner. The baseline NRI of patients was calculated using serum albumin level and body mass index, and a malnutrition status was defined as NRI ≤ 98. Univariate and multivariate logistic regression analyses were conducted to identify predictors for ECE and SVI. Nomograms for predicting ECE and SVI were established based on the results of the multivariate logistic regression analysis. The performance of the nomograms was estimated using Harrell\'s concordance index (C-index), the area under curve (AUC) of receiver operating characteristic (ROC) curves and the calibration curves.
UNASSIGNED: In the primary cohort, 70 (14.3%) patients with NRI ≤ 98 were classified as malnutrition, while the remaining 419 (85.7%) patients with NRI > 98 were considered to have normal nutrition. The nomograms for predicting ECE and SVI shared common factors including NRI, percentage of positive biopsy cores (PPC) and biopsy Gleason score, while prostate-specific antigen (PSA) levels and PSA density (PSAD) were only incorporated in ECE nomogram. The C-indexes of the nomograms for predicting ECE and SVI were 0.785 (95% confidence interval (CI): 0.745 - 0.826) and 0.852 (95% CI: 0.806 - 0.898), respectively. The calibration curves demonstrated excellent agreement between the predictions by the nomograms and the actual observations. The results remained reproducible when the nomograms were applied to the validation cohort.
UNASSIGNED: The NRI is significantly associated with ECE and SVI in PCa patients. The nomogram established based on the NRI in our study can provide individualized risk estimation for ECE and SVI in PCa patients, and may be valuable for clinicians in making well-informed decisions regarding treatment strategies and patient management.

OBJECTIVE: Prostate-specific antigen (PSA) is thought to be undetectable (< 0.1 ng/mL) after radical prostatectomy (RP), and persistent PSA (≥ 0.1 ng/mL) is considered a failure of curative treatment.
METHODS: The study population consisted of 135 patients, all of whom underwent RP for localized prostate cancer, and developed persistent PSA. We set the starting point at the timing of RP, and the endpoints were the development of castration-resistant prostate cancer (CRPC) and cancer-specific survival.
RESULTS: Salvage radiation therapy (RT) and androgen deprivation therapy (ADT) were performed in 53 (39.3%) and 64 (47.4%) patients, respectively. Eighteen (13.3%) patients didn\'t receive any salvage treatment. During the median follow-up of 10.1 years, CRPC was observed in 23 patients, and 6 patients died due to prostate cancer. Kaplan-Meier curves demonstrated the 15-year CRPC-free and cancer-specific survivals were 79.5% and 92.7%, respectively. Cox multivariate analysis demonstrated that seminal vesicle invasion (SVI) (p = 0.007) and nadir PSA ≥1.0 ng/mL (p = 0.002) were independent risk factors for CRPC. Salvage RT demonstrated better cancer control (the 10-and 15-year CRPC-free survival was 94.1% and 94.1%) compared to ADT (75.9% and 58.5%, p = 0.017) after 1:1 propensity score matching.
CONCLUSIONS: SVI and nadir PSA ≥1.0 ng/mL are independent risk factors for CRPC in patients with persistent PSA after RP. Salvage RT is considered to be the optimal treatment for this condition.

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.
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.
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.
Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns.

BACKGROUND: 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.
CONCLUSIONS: 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.

Locally advanced prostate cancer (PCa) with pathological seminal vesicle invasion (pT3b) is a very-high-risk disease associated with biochemical recurrence (BCR), local recurrence, distant metastases, or mortality following definitive therapies. This study aimed to evaluate the risk factors associated with BCR following robot-assisted radical prostatectomy (RARP) in PCa patients with pT3b. A retrospective multicenter cohort study was conducted on 3,195 patients with PCa who underwent RARP at nine domestic centers between September 2011 and August 2021. Biochemical recurrence-free survival (BRFS) after RARP in PCa patients with pT3b was the primary end-point of the study. The secondary end-point was to determine the association between BCR and covariates. We enrolled 188 PCa patients with pT3b. The median follow-up period was 32.8 months. At the end of the follow-up period, 76 patients (40.4%) developed BCR, of whom 15 (8.0%) were BCR at the date of surgery. The 1-, 2-, and 3-year BRFS rates were 76.4, 65.9, and 50.8%, respectively. Multivariate analysis identified initial prostate-specific antigen level and positive surgical margins (PSM) as significant predictors of BCR in PCa patients with pT3b undergoing RARP. In this study, we investigated the BRFS in PCa patients with pT3b. As PSM was an independent predictor of BCR in PCa patients with pT3b, these patients may require a combination of therapies to improve the BCR.

The purpose of this study was to analyze the value of transrectal shear-wave elastography (SWE) in combination with multivariable tools for predicting adverse pathological features before radical prostatectomy (RP). Preoperative clinicopathological variables, multiparametric magnetic resonance imaging (mp-MRI) manifestations, and the maximum elastic value of the prostate (Emax) on SWE were retrospectively collected. The accuracy of SWE for predicting adverse pathological features was evaluated based on postoperative pathology, and parameters with statistical significance were selected. The diagnostic performance of various models, including preoperative clinicopathological variables (model 1), preoperative clinicopathological variables + mp-MRI (model 2), and preoperative clinicopathological variables + mp-MRI + SWE (model 3), was evaluated with area under the receiver operator characteristic curve (AUC) analysis. Emax was significantly higher in prostate cancer with extracapsular extension (ECE) or seminal vesicle invasion (SVI) with both P < 0.001. The optimal cutoff Emax values for ECE and SVI were 60.45 kPa and 81.55 kPa, respectively. Inclusion of mp-MRI and SWE improved discrimination by clinical models for ECE (model 2 vs model 1, P = 0.031; model 3 vs model 1, P = 0.002; model 3 vs model 2, P = 0.018) and SVI (model 2 vs model 1, P = 0.147; model 3 vs model 1, P = 0.037; model 3 vs model 2, P = 0.134). SWE is valuable for identifying patients at high risk of adverse pathology.

Background and Objectives: Patients with seminal vesicle invasion (SVI) are a highly heterogeneous group. Prognosis can be affected by many clinical and pathological characteristics. Our aim was to study whether bilateral SVI (bi-SVI) is associated with worse oncological outcomes. Materials and Methods: This is an observational retrospective study that included 146 pT3b patients treated with radical prostatectomy (RP). We compared the results between unilateral SVI (uni-SVI) and bi-SVI. The log-rank test and Kaplan-Meier curves were used to compare biochemical recurrence-free survival (BCR), metastasis-free survival (MFS), and additional treatment-free survival. Cox proportional hazard models were used to identify predictors of BCR-free survival, MFS, and additional treatment-free survival. Results: 34.93% of patients had bi-SVI. The median follow-up was 46.84 months. No significant differences were seen between the uni-SVI and bi-SVI groups. BCR-free survival at 5 years was 33.31% and 25.65% (p = 0.44) for uni-SVI and bi-SVI. MFS at 5 years was 86.03% vs. 75.63% (p = 0.1), and additional treatment-free survival was 36.85% vs. 21.93% (p = 0.09), respectively. In the multivariate analysis, PSA was related to the development of BCR [HR 1.34 (95%CI: 1.01-1.77); p = 0.03] and metastasis [HR 1.83 (95%CI: 1.13-2.98); p = 0.02]. BCR was also influenced by lymph node infiltration [HR 2.74 (95%CI: 1.41-5.32); p = 0.003]. Additional treatment was performed more frequently in patients with positive margins [HR: 3.50 (95%CI: 1.65-7.44); p = 0.001]. Conclusions: SVI invasion is an adverse pathology feature, with a widely variable prognosis. In our study, bilateral seminal vesicle invasion did not predict worse outcomes in pT3b patients despite being associated with more undifferentiated tumors.