Clinical significance of prostate cancer identified by transperineal standard template biopsy in men with nonsuspicious multiparametric magnetic resonance imaging.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csCaP). However, whether a negative mpMRI in patients with a clinical suspicion of CaP can omit a confirmatory biopsy remains less understood and without consensus. Transperineal (TP) standard template biopsy (SBx) provides an effective approach to CaP detection. Our aim is to provide a comprehensive understanding of the CaP characteristics detected through TP SBx that are systematically overlooked by mpMRI. METHODS: We conducted a retrospective analysis of all men who underwent prebiopsy mpMRI and subsequent a 20-core TP SBx at our hospital from September 2019 to February 2021. Patients with suspicious mpMRI received a combined TP SBx and targeted biopsy (TBx) (suspicious group), while those without suspicious (negative) mpMRI and who proceeded to biopsy, received TP SBx only (nonsuspicious group). A negative mpMRI was defined as the absence of suspicious findings and/or the presence of low-risk areas with a PI-RADS score of ≤2. Subsequently, we compared and evaluated the clinical and biopsy characteristics between these 2 groups. RESULTS: We identified 301 men in suspicious group and 215 men in nonsuspicious group. The overall CaP detection rate and csCaP detection rate by TP SBx were 74.1%, 38.9% for suspicious group and 43.3%, 14.9% for nonsuspicious group, respectively. csCaP NPV of mpMRI was 85.1% with a csCaP prevalence 28.9%. The greatest percentage of cancer involvement (GPC) in biopsy core from nonsuspicious group was significantly lower than those of suspicious group (40% vs. 50%, p = 0.005), In multivariate logistic analysis, only PSAD > 0.15 ng/ml/cc was identified as an independent and significant predictor of csCaP in nonsuspicious group. CONCLUSION: Within our cohort, false-negative rates of mpMRI for csCaP are substantial, reaching 15%. Nonsuspicious cases may contain a large volume tumor since the high GPC of SBx. For cases with nonsuspicious imaging and higher PSAD, a confirmatory biopsy may be necessary due to the increased risk of missed csCaP by mpMRI.

Estimated Prostate Volume by Semiautomatic Segmentation of MRI Is More Accurately Correlated with Radical Prostatectomy Specimen Weight than the Volume Calculated by Ellipsoid Formula.

INTRODUCTION: Accurate in vivo prostate volume (PV) estimation is important for obtaining prostate-specific antigen density (PSAD) and further predicting clinically significant prostate cancer (csPCa). We aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI)-estimated PV compared to both volume and weight of radical prostatectomy (RP). METHODS: We identified 310 PCa patients who underwent RP following combined targeted and systematic biopsy in our institution from September 2019 to February 2021. The MRI PV was determined using a semiautomated segmentation algorithm. RP PV was calculated using the prolate ellipsoid formula (length × width × height × π/6). Formula (prostate weight = [actual weight-3.8 g]/1.05 g/mL) was applied, and the resulting volume was used in further analysis. RESULTS: The median PV from MRI, RP, and RP weight were 39 mL, 38 mL, and 44 mL, respectively. Spearman's rank correlation coefficients (ρ) were 0.841 (MRI PV vs. RP weight), 0.758 (RP PV vs. RP weight), and 0.707 (MRI PV vs. RP PV) (all p < 0.001). Decreased correlation between the MRI PV and RP PV was observed in the larger (more than 55 mL) prostate. The PSAD derived from MRI PV showed most efficient to detect csPCa in RP specimen (57.9% vs. 57.6% vs. 45.4%). CONCLUSION: MRI PV is correlated better with RP weight than calculated RP PV, especially in larger prostate. The high csPCa detection rate in final pathology suggested that PSAD derived from MRI PV can be confidently used in clinical practice.

Detection of extraprostatic extension by transperineal multiparametric magnetic resonance imaging-ultrasound fusion targeted combined with systemic template prostate biopsy.

BACKGROUND: Extraprostatic extension (EPE) of prostate cancer (PCa) on transrectal (TR) needle core biopsy (Bx) is a rare histopathological finding that can help in clinical decision-making. The detection efficiency of the transperineal (TP) approach is yet to be explored. METHODS: We retrospectively reviewed 2848 PCa cases using concomitant systemic template biopsy (SBx) and multiparametric magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy (TBx) using the TR (n = 1917) or TP (n = 931) approach at our institution between January 2015 and July 2022. We assessed and compared clinical, MRI, and biopsy characteristics using different approaches (TP and TR) and methods (SBx and TBx). RESULTS: In total, 40 EPE cases were identified (40/2848, 1.4%). TP showed a significantly higher EPE detection rate compared to TR in SBx (TR:0.7% vs. TP:1.6%; p = 0.028) and TBx (TR:0.5% vs. TP:1.2%; p = 0.033), as well as the combined methods (2.1% vs. 1.1%, p = 0.019). A significantly higher incidence of EPEs was found at non-base sites in TP than in TR (76.7% vs. 50%, p = 0.038). SBx showed a higher EPE detection rate than TBx; however, the difference was not statistically significant. TP showed higher prostate-specific antigen density (0.35 vs. 0.17, p = 0.005), higher frequency of GG4-5 in the cores with EPE (65.0% vs. 50.0%, p = 0.020), and more PCa-positive SBx cores (10 vs. 8, p = 0.023) compared to the TR. CONCLUSIONS: TP may improve EPE detection compared with TR and should be applied to patients with adverse pre-biopsy features.

Clinicopathological and oncological significance of persistent prostate-specific antigen after radical prostatectomy: A systematic review and meta-analysis.

Objective: To investigate the association of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) with clinicopathological features and long-term oncological prognosis for the development of a potential management strategy. Methods: A systematic literature search was performed using PubMed and Web of Science up to June 2021 to identify the eligible studies focusing on understanding the impact of persistent PSA in patients who underwent RP for localized prostate cancer. Meta-analyses were performed on parameters with available information. Results: A total of 32 RP studies were identified, of which 11 included 26 719 patients with consecutive cohorts and the remaining 21 comprised 24 177 patients with cohorts carrying specific restrictions. Of the 11 studies with consecutive cohorts, the incidence of persistent PSA varied between 3.1% and 34.6% with a median of 11.0%. Meta-analyses revealed patients with persistent PSA consistently showed unfavorable clinicopathological features and a more than 3.5-fold risk of poorer biochemical recurrence, metastasis, and prostate cancer-specific mortality prognosis independently, when compared to patients with undetectable PSA. Similarly, cases with persistent PSA in different specific patient cohorts with a higher risk of prostate cancer also showed a trend of worse outcomes. Conclusion: We found that the frequency of persistent PSA was about 11.0% in consecutive RP cohorts. Persistent PSA was significantly associated with unfavorable clinicopathological characteristics and worse oncological outcomes. Patients with persistent PSA after RP may benefit from early salvage treatment to delay or prevent biochemical recurrence, improving oncological outcomes for these patients. Further prospective randomized controlled trials are warranted to understand optimal systemic therapy in these patients.

Gleason Grade Group Concordance between Systematic Template Combining Magnetic Resonance Imaging Fusion Targeted Biopsy and Radical Prostatectomy Specimens: A Comparison of Transperineal and Transrectal Approaches.

OBJECTIVE: To evaluate the Gleason grade (GG) discrepancy between biopsy (Bx) techniques (transperineal [TP] /transrectal [TR] approaches or multiparametric magnetic resonance imaging [mpMRI] targeted biopsy [TBx] / standard template biopsies [SBx]) and radical prostatectomy (RP) specimens. PATIENTS AND METHODS: We identified 310 prostate cancer (PCa) patients who underwent RP following either TP TBx combining SBx (20-core) (n = 105) or TR TBx combining SBx (12-core) (n = 205) from September 2019 to February 2021. The Bx GG was based on the core with the highest GG and clinically significant PCa (csPCa) was defined as grade group 2 or greater prostate adenocarcinoma. RESULTS: TP combined TBx and SBx (CBx) showed a better GG concordance (63.8% vs 57.1%) than the TR approach, but did not reach a statistical significance. TBx demonstrated a significantly higher csPCa detection than SBx in all patients including both approaches (70.2% vs 63.9%, P < .001). TR TBx showed a significantly higher concordance than TR SBx (52.2% vs 41.5%, P = .0.002) while TP TBx did not differ from TP SBx. TP CBx showed the highest Kappa coefficient (κ =0.48) followed by TR CBx (κ = 0.39). Thirty-eight of 69 (55.1%) cases with a GG1 diagnosis in CBx were upgraded to csPCa in RP. TR approach showed a trend of 2.8-fold risk to upgrade to RP csPCa than TP approach (P = .0.065). CONCLUSION: The combination of SBx and TBx led to a better pathological concordance and lower upgrading rate for both TP and TR approaches to RP. With more SBx cores, TP CBx showed a better performance than TR CBx.

Detection of clinically significant prostate cancer by transperineal multiparametric magnetic resonance imaging-ultrasound fusion targeted prostate biopsy in smaller prostates.

PURPOSE: Transperineal (TP) multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) has been shown to detect more clinically significant (cs) prostate cancer (PCa) than standard template biopsies (SBx). Current data supports the inclusion of both TBx and SBx in obtaining an optimal csPCa detection rate. We compared csPCa detection rates in patients with different prostate volumes to examine the benefit of performing TBx in smaller prostates through the TP approach. METHODS: We identified all men who with suspicious lesions on mpMRI and underwent TP TBx (3-core) and concomitant SBx (20-core) in our single hospital from September 2019 to February 2021. Clinical, MRI and biopsy pathological characteristics were evaluated and compared between TBx and SBx. Grade group 2 or greater prostate adenocarcinoma was defined as csPCa. RESULTS: Three hundred and one (n = 301) men were included. The median prostate volume by MRI was 45 ml. The patients were divided by prostate volume into three groups: ≤30ml group (19.9%), >30 to ≤45 ml group (31.3%) and >45ml group (48.8%). Patients in the ≤30ml group showed significantly higher frequency of combined (both TBx and/or SBx) csPCa detection rate (65.0%) than patients in the >45ml group (39.5%) but similar frequency to the >30 to ≤45 ml group (54.2%,). By TBx only (55.0% vs 27.9%) or by SBx only (56.7% vs. 34.0%), patients in the ≤30ml group consistently showed significantly higher rates of csPCa detection than patients in the >45 ml group. In the ≤30ml group, the detection rate of csPCa was comparable by TBx, SBx or when combined. Four of 6 csPCa cases missed by TBx but detected by SBx were present at the base location. CONCLUSION: Our data suggest that performing TBx with limited additional cores may potentially achieve the same csPCa detection rate as the combined SBx and TBx in smaller prostates.

Transperineal Multiparametric Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy Combined with Standard Template Improves Prostate Cancer Detection.

PURPOSE: Transperineal (TP) prostate biopsy provides an effective approach to prostate cancer (PCa) detection. Although transrectal targeted biopsy has been well described, the specific advantage of the standard TP template or TP targeted biopsy using multiparametric (mp) magnetic resonance imaging (MRI)-ultrasound (US) fusion remains less understood and without consensus. MATERIALS AND METHODS: We identified all men who underwent a transperineal standard 20-core template in addition to a targeted biopsy with mpMRI-US fusion-guided software from September 2019 to February 2021. We assessed and compared clinical, MRI and biopsy characteristics between standard TP template and fusion targeted biopsies. RESULTS: A total of 301 men underwent TP fusion biopsy during the study period. Target lesions on MRI were sampled with 3 targeted cores per patient (IQR 3-4). The overall cancer detection rate was 74.1% and 63.5% by standard template and targeted biopsy, respectively, of which 52.5% and 59.7% were clinically significant (cs) PCa. Combined csPCa detection rate was 62.2%. Of 176 cases with a cancer diagnosis by both biopsy methods, 18.8% were upgraded with targeted biopsies while 18.2% were upgraded with template biopsies. CONCLUSIONS: In men with suspicious lesions on mpMRI, TP MRI fusion-guided biopsies combined with standard template provide a higher overall cancer detection rate and higher detection rate of csPCa than the standard template or targeted biopsy alone. In the setting of a suspicious mpMRI prostate lesion, targeted plus standard template should be included as part of the TP biopsy procedure.

Transperineal multiparametric magnetic resonance imaging-ultrasound fusion-targeted prostate biopsy combined with standard template improves perineural invasion detection.

Perineural invasion (PNI) on biopsy is associated with adverse features in prostate cancer (PCa). Transrectal multiparametric magnetic resonance imaging (MRI)-targeted biopsy (TBx) has shown to detect higher presence of PNI than standard template biopsy (SBx). Transperineal biopsy provides effective cancer detection with lower complications than the transrectal approach. We compared PNI detection efficiency between SBx and TBx through transperineal approach. We identified patients with PCa who underwent transperineal TBx and concomitant standard 20-core template SBx from September 2019 to February 2021. Clinical, MRI imaging and biopsy characteristics were evaluated and compared between TBx and SBx. Two hundred thirty-eight patients with PCa underwent concomitant transperineal SBx and TBx procedures. Combined PNI+ (SBxPNI+ and/or TBxPNI+) was identified in 77 of 238 (32.4%) patients. SBx detected 23.9% PNI-positive patients and TBx detected 19.3% PNI-positive patients of all patients with PCa. Patients with PNI were with significantly different clinicopathological characteristics than patients without PNI. Although significantly more positive PCa cores and higher positive PCa core rate were found in the SBx method, patients with SBxPNI+ only shared similar features as TBxPNI+only patients. Of 176 cases with both SBxPCa and TBxPCa, TBx could detect 19 (15.1%) more PNI cases than SBx while SBx could detect 24 (18.3%) more PNI cases than TBx. Multiparametric MRI fusion-targeted biopsy in combination with template biopsy through transperineal approach achieved PNI detection rate over 30% of PCa cases. The increased PNI detection may improve the model to select active surveillance candidates in clinical practice.

Long-term Oncologic Impact of Positive Anterior and Posterior Surgical Margins After Radical Prostatectomy.

OBJECTIVE: The objective of this study was to evaluate the impact of the anterior/posterior status of positive surgical margin (PSM) on long-term outcomes after radical prostatectomy for prostate cancer. PATIENTS AND METHODS: We included 391 consecutive PSM patients after radical prostatectomy between 1993 and 2007 excluding cases with multiple location PSM or lack of anterior/posterior status data. The oncologic impact of anterior-PSM and posterior-PSM were examined by Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: There were 115 cases (29.4%) with apex-PSM, 257 cases (65.7%) with peripheral PSM, and 19 cases (4.9%) with bladder neck PSM. Among the 257 peripheral PSM cases, 58 cases (22.6%) were with anterior-PSM, 174 cases (67.7%) were with posterior-PSM, and 25 cases (9.7%) were with both anterior and posterior PSM. Over a median follow-up of 12.6 years, patients with anterior-PSM, especially those with low to intermediate Gleason score (≤7), showed a biochemical recurrence (BCR) prognosis similar to those with apex-PSM. In contrast, patients with posterior-PSM showed significantly higher BCR risk on both univariate and multivariate analyses when compared with those with apex-PSM. No impact on metastasis-free survival or overall survival was observed. CONCLUSIONS: In our study, we found that prostate cancer patients with anterior-PSM showed a more favorable BCR prognosis similar to those with apex-PSM when comparing to patients with posterior-PSM. Our study results may help physicians to choose different treatment options for patients diagnosed with different PSM status including considering further adjuvant treatment for patients with posterior-PSM.

Impact of biopsy perineural invasion on younger prostate cancer patients after radical prostatectomy.

OBJECTIVES: To identify the potential indicators for higher-risk disease and poor outcome in younger prostate cancer (PCa) patients (age ≤ 50) who had undergone radical prostatectomy (RP) in the prostate-specific antigen (PSA) era. MATERIALS AND METHODS: A total of 186 PCa cases of age ≤ 50 who underwent RP between 2003 and 2010 at our center were included for study. High-risk disease after RP was defined as cases with pre-PSA ≥ 20 ng/ml and/or Gleason score (GS) ≥ 4 + 3 and/or pT stage ≥ 3. The poor outcome group was defined as cases with biochemical recurrence (BCR) and/or metastasis (Mets) and/or all-cause death. Multivariate logistic regression models were performed to identify independent risk factors for both high-risk disease and poor outcome. RESULTS: Among 186 younger PCa patients aged ≤ 50, 36 cases (19.5%) had high-risk disease and 24 cases (12.9%) had poor outcome. The presence of biopsy perineural invasion (BxPNI) was significantly associated with high-risk disease and showed a trend to correlate with worse outcome in univariate analysis. On multivariate logistic regression analysis, BxPNI was shown to be a significant independent risk factor with covariate of D'Amico for poor outcome (p = 0.047) and an independent risk factor with covariate of BxGPC for high-risk PCa excepting the variables to define high-risk disease (p = 0.013). Prognostically, cases with BxPNI showed a poor BCR-free survival in univariate analysis but did not reach significance (p = 0.063). CONCLUSION: Our results show that BxPNI could be considered as a risk classification factor to identify the best candidates among younger PCa patients for further treatment and may also be used for developing active surveillance (AS) selection criteria for younger PCa patients.

Clinicopathological characteristics of localized prostate cancer in younger men aged ≤ 50 years treated with radical prostatectomy in the PSA era: A systematic review and meta-analysis.

OBJECTIVES: With the rapid increase in younger age prostate cancer (PCa) patients, the impact of younger age on decision-making for PCa treatment needs to be revaluated in the new era. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, EMBASE, and Web of Science up to October 2019 to identify the eligible radical prostatectomy (RP) studies focusing on understanding the impact of age on clinicopathological features and oncological prognosis in patients with localized PCa in PSA era. Meta-analyses were conducted using available hazard ratios (HRs) from both univariate and multivariate analyses. RESULTS: Twenty-six studies including 391 068 patients with RP treatments from the PSA era were included. Of these studies, age of 50 years old (age50) is the most commonly used cut-off age to separate the younger patient group (including either age < 50 or age ≤ 50) from the older patient group. In these studies, the incidence of younger patients varied between 2.6% and 16.6% with a median of 8.3%. Younger patients consistently showed more favorable clinicopathological features correlated with better BCR prognosis. Meta-analyses showed a 1.38-fold improved BCR survival of younger patients in multivariate analysis. Among the high-risk PCa patients, younger age was independently associated with worse oncological outcomes in multivariate analyses. CONCLUSION: In this study, we found younger age correlated with favorable clinicopathological characteristics and better BCR prognosis in low- to intermediate-risk patients. In high-risk group patients, younger patients often showed significantly worse oncological outcomes. Our study results suggest that age 50 could be used as a practical cut-off age to separate younger age patients from older age PCa patients.

Quantification of perineural invasion focus after radical prostatectomy could improve predictive power of recurrence.

Perineural invasion (PNI) after radical prostatectomy (RP) is a common feature of prostate cancer (PCa) and has been associated with unfavorable tumor characteristics. However, its prognostic relevance is controversial. In this study, we evaluated the impact of both PNI status (PNI+ versus PNI-) and quantified number of PNI focus on the long-term prognosis of biochemical recurrence (BCR) after RP. After reevaluating PNI of a total of 721 patients with localized PCa who underwent RP at our institution between 2000 and 2002, we examined associations between PNI status or PNI focus number and clinicopathological factors including tumor stage, Gleason score, margin status, tumor location, preoperative prostate specific antigen, age, prostate weight as well as BCR outcome. PNI was present in 530 of 721 cases (73.5%) of the RP specimens and was associated with more aggressive disease. BCR occurred in 19.4% of all patients within a median follow-up period of 8.5 years. PNI+ status was associated with poor BCR prognosis in univariate analysis but lost in multivariate analysis. Based on the number of PNI focus, PNI was further divided into 2 distinct group: PNI+ a (≤3) and PNI+ b (>3). In a multivariate Cox regression model, PNI+ b (>3) was identified as an independent BCR prognostic factor. Quantification of PNI focus number beside the dichotomized status recording will not only provide more detailed information but also be a novel prognostic indicator for risk stratification. Further external validation will be needed for an optimal cut-off value of the PNI focus number. Our findings will help further research on the relevance of PNI in the pretreatment setting and support ongoing efforts to understand its role of cancer progression.

The clinicopathological characteristics and prognostic value of squamous differentiation in patients with bladder urothelial carcinoma: a meta-analysis.

PURPOSE: Urothelial carcinoma with squamous differentiation (UCSD) is the most common histologic variant in bladder cancer (BCa). Previously, some studies have linked the presence of UCSD with the risk of worse survival outcomes in BCa patients. However, such association is still controversial. In this study, we performed a meta-analysis to clarify the clinicopathological characteristics and to further investigate the prognostic value of UCSD in BCa. METHODS: A systematic literature search was performed in electronic databases including PubMed, Embase, Chinese National Knowledge Infrastructure and Wanfang Data until October 2018. Subgroup analyses were performed according to different treatments and study outcomes. RESULTS: Total of 13,284 patients were enrolled in 19 studies which were included in this meta-analysis. The percentage of female patients with UCSD was significantly higher than those with pure urothelial carcinoma. UCSD was correlated with tumor stage T3/T4, tumor grade 3, positive surgical margin, and lymph node involvement. Moreover, the recurrence rate was higher in patients with UCSD after surgery. UCSD was associated with poorer disease-free survival (DFS). No significant difference of cancer-specific survival (CSS) or overall survival (OS) was found on multivariable analysis between the two groups. CONCLUSIONS: Our study demonstrated that UCSD in BCa was associated not only with unfavorable clinicopathological features, but also with high risk of recurrence and poorer prognosis for DFS. However, UCSD is not independently significant for CSS and OS. Well-designed randomized study with larger sample size is warranted to verify the findings and to further explore the role of UCSD in BCa.

Impact of biopsy perineural invasion on the outcomes of patients who underwent radical prostatectomy: a systematic review and meta-analysis.

Objectives: To investigate the association between biopsy perineural invasion (PNI) and oncological outcomes of prostate cancer (PCa) after radical prostatectomy (RP).Materials and methods: A systematic literature search was performed using PubMed, EMBASE and Web of Science up to December 2018 to identify the eligible studies that included localized PCa patients who underwent biopsy and subsequently RP as well as follow-up information. Meta-analyses were conducted using available hazard ratios (HRs) of biopsy PNI from both univariate and multivariate analyses.Results: Eighteen studies including 14,855 patients with treatment follow-up information were included in the current systematic review. The rate of biopsy PNI varied between 7.0% and 33.0%. Seven out of the 18 studies that demonstrated biopsy PNI were associated with adverse pathologic features. Thirteen out of the 18 studies showed biopsy PNI correlated significantly with higher rates of biochemical recurrence (BCR)/cancer progression status or worse prognostic outcomes. With pooled data based on four studies with available univariate analysis results and four studies with multivariate analysis, statistically significant associations were found between biopsy PNI and BCR with univariate analysis (HR = 2.05; 95% CI = 1.57-2.68; p < 0.001) and with multivariate analysis (HR = 1.57; 95% CI = 1.28-1.93; p < 0.001).Conclusion: Evidence from the included observational studies indicated that biopsy PNI was not only correlated with adverse pathologic characteristics but also with worse BCR prognosis of local PCa after RP. The status of biopsy PNI could serve as a promising risk-stratification factor to help the decision-making process, considering active surveillance (AS) or further treatment for PCa patients.

Assessment of 5-year overall survival in bladder cancer patients with incidental prostate cancer identified at radical cystoprostatectomy.

OBJECTIVE: To investigate the oncological impact of incidental prostate cancer (iPCa) found during radical cystoprostatectomy (RCP) on overall survival (OS) prognosis of urothelial carcinoma of the bladder (BCa). PATIENTS AND METHODS: A total of 122 RCP cases resected between 2002 and 2012 at our center were included for study. Survival of BCa patient was compared using the Kaplan-Meier method and the log-rank test. Cox proportional hazards regression models were used to analyze the impact of iPCa on the 5-year overall mortality of BCa patients after RCP. RESULTS: Among the 122 BCa cases that underwent RCP, 38 cases (31.1%) had iPCa, in which, 17 cases (44.7%) were identified as clinically significant iPCa (csPCa). BCa patients with iPCa were older (71 vs 64 years, p = 0.004) and had higher preoperative PSA level (3.1 ng/mL vs 1.4 ng/mL, p = 0.017) when compared to those without iPCa. Cases with iPCa showed a more favorable 5-year OS than cases without iPCa, although this difference did not reach statistical significance (p = 0.219). When excluding the higher risk cases with Gleason score (GS) ≥ 4 + 3 and/or preoperative PSA > 10 ng/mL, BCa patients with iPCa showed a significantly longer OS than cases without iPCa on univariate analysis (p = 0.044), but not on multivariate analysis (p = 0.125). CONCLUSION: Our results demonstrated that the frequent findings of low-risk iPCa in BCa patients could indicate the potential possibility of shared pathogenesis pathways between iPCa and BCa. Future study with a larger cohort is warranted to validate this result.

Expression of PD-L1 in tumor-associated nerves correlates with reduced CD8+ tumor-associated lymphocytes and poor prognosis in prostate cancer.

To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD-L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD-L1 was frequently observed in the nerve branches in the tumor-associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3-, CD3- and CD8-positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD-L1+ tumor-associated nerves (TANs) was inversely correlated with that of CD8+ TALs. Higher density of PD-L1+ TANs was significantly associated with biochemical recurrence (BCR) in Kaplan-Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD-L1+ TANs was independently prognostic of BCR. In conclusion, PD-L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8+ TALs. Neuro-immunological interaction may be a contribution to immune-suppressive microenvironment. Combinatorial treatment regimen designs to neural PD-L1 and TALs should be warranted in future clinical application of anti-PD-L1/PD-1 immunotherapy in prostate cancer.

Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome.

OBJECTIVE: To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality. PATIENTS AND METHODS: From a total of 2796 cases of RP between 1993 and 2007 in our single hospital, 476 cases with PSMs were identified and included in this study. PSM location was categorized into apex, peripheral, and bladder neck. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze the impact of PSM focality and location status on oncologic survival. RESULTS: Of these 476 cases with PSMs, 335 (70.4%) cases were with single focal (sF) PSMs and 141 (29.6%) cases were with multifocal (mF) PSMs. Furthermore, 406 (85.3%) cases were found to have single location (sL) PSMs, and 70 (14.7%) cases were with multilocation (mL) PSMs. The median follow-up was 12.9 years. mF-PSMs and mL-PSMs showed significant impact on increased BCR risk on univariate analysis, and mL-PSMs remained significant on multivariate analysis (P = .048). Furthermore, the combination of multifocality and multilocation showed added prognostic value on predicting BCR-free survival, but not on metastasis-free survival or overall survival. CONCLUSION: The presence of mF-PSMs and mL-PSMs, and especially the combination of both, demonstrated significant impact on BCR prognosis. Patients with apex sLsF-PSMs were less likely to have BCR when compared with all those with non-apex sLsF-PSMs. These results should be considered when evaluating patients for adjuvant therapy.

Expression of aromatase in tumor related stroma is associated with human bladder cancer progression.

Putative gender differences in bladder cancer (BCa) have been proposed to result from sex hormone influence. Aromatase is the key enzyme catalyzing the conversion of androgens to estrogens which may result in an intratumoral microenviroment with increased estrogen production. In this study, we investigated the expression pattern of aromatase and its association with BCa progression. Tissue samples from 88 BCa patients who underwent cystectomy were obtained. Using immunohistochemistry (IHC), expression of aromatase in tumor epithelium (TE) and tumor related stroma (TS) were evaluated separately, and the association of aromatase expression status with pathologic variables and overall survival (OS) outcome was examined. High aromatase expression was found in 33/88 (37.5%) of TE and in 65/88 (73.9%) of TS. Increased aromatase expression in TE had a trend to correlate with male gender. Increased aromatase in TS was significantly associated with adverse pathologic variables including higher pathologic pT, positive lymph node metastasis (pN), lymphovascular invasion (LVI), and distant metastasis. In univariate analysis, high aromatase expression in TS was significantly associated with poorer overall survival (p = 0.014), but this association was not significant (p = 0.163) in multivariate cox analysis adjusted for independent factors including age at surgery and pN. These results demonstrate that aromatase expression in TS but not TE may play a critical role in BCa progression. Our findings provide direct evidence of aromatase involvement in BCa and suggest endocrine therapy may have a potential role in the treatment of BCa.

Expression of CD147 is associated with prostate cancer progression.

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. Kaplan-Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.