Radical Prostatectomy Specimens Research Articles

Collision tumors revealed by prospectively assessing subtype-defining molecular alterations in 904 individual prostate cancer foci

BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).

A genomic classifier for prostate cancer correlates with adverse pathologic features: Transcriptomic features of cribriform and intraductal carcinoma of the prostate.

268 Background: Invasive cribriform and intraductal carcinoma (CF/IDC) portends an unfavorable prognosis for patients diagnosed with prostate cancer (CaP). Limited studies with small sample sizes have explored whether genomic classifiers are associated with IDC and/or CF status. We investigated the correlation between Decipher genomic risk score and IDC/CF status and assessed PCa transcriptomic features. Methods: We performed a retrospective review of CaP patients who had Decipher testing at a single high volume center between 2009-2020. The highest grade index lesion from radical prostatectomy specimens was identified by GU pathologists and used for Decipher testing. Genitourinary pathologists reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were divided into three groups based on pathologic features, absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Multivariable logistic regression was used to identify predictors of high-risk Decipher GC scores. The Kaplan-Meier method with log-rank was used to compare biochemical recurrence free survival. Differential gene expression and gene network analysis was used to identify genes and pathways associated with IDC/CF features. Results: 463 patients were included with a median follow-up of 25 months. Patients who were CF+/IDC+ had higher GC scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p<0.001). Patients who were CF+/IDC+ had a higher percentage of Gleason grade group >3 (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p<0.001). On multivariate logistic regression, predictors of high-risk GC score were presence of CF+/IDC+ features on final pathology (OR: 3.94, p<0.001) and pathologic Gleason grade group >3 (OR: 1.58, p=0.04). Transcriptomic analysis revealed that the hallmark androgen response pathway was significantly upregulated in CF+/IDC+ patients (Log fold change: 15.7, p<0001). Conclusions: This is the largest series investigating the association of a clinically validated genomic classifier and pathologic features such as cribriform and intraductal carcinoma. These findings have implications for the use of genomic classifiers in settings where expert GU pathology is not readily available and in potentially unmasking adverse histology at the time of biopsy.[Table: see text]

Salvage radiotherapy (SRT) in combination with pembrolizumab in patients with PSA persistence or biochemical recurrence after radical prostatectomy due to prostate cancer.

TPS212 Background: Goal of our study is to evaluate the efficacy and safety of immunotherapy in combination with standard salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) or prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). The combination of immunotherapy (IO) with radiation therapy might provide a clinical benefit to patients with recurrent prostate cancer due to an induction of increased activity of the immune system against cancerous tissue (abscopal effect). Primary endpoint is complete biochemical response (PSA level below detection level) 60 weeks after start of trial treatment, which further defines prognosis of patients. Further explorative endpoints like radiographic progression-free survival, PSA-nadir level and time to PSA-nadir, time to initiation of subsequent therapy (secondary ADT or NHA) and quality of life as well as adverse events will be evaluated. Methods: The trial is as a phase II, open-label, single arm monocenter trial which evaluates the combination of pembrolizumab as study medication in combination with SRT. Pembrolizumab will be administered in a three-weekly scheme up to one year of treatment. A concomitant ADT is administered in high-risk patients only (PSA > 0.7ng/ml or cN+ in imaging studies). All patients will be staged with PSMA PET-CT, if applicable. Additionally, blood and urine samples will be collected for correlative biomarker studies. A total of 49 patients are planned to be enrolled in this explorative study within 2 years. INCLUSION CRITERIA (excerpt) Histologically confirmed diagnosis of an adenocarcinoma of the prostate and a BCR or PSA persistence after RP. Histology of the RP specimen needs to fulfill the following criteria: adenocarcinoma of the prostate, Gleason score 7-10; pNX or pN0 or pN1 (max. 2 lymph nodes involved). Imaging within 30 days prior to study inclusion is mandatory (([68Ga] or [18F] PSMA PET-CT as standard imaging modality, alternatively CT abdomen and full-body bone scan). PSA value between ≥0.2 and ≤1.0 ng/ml, measured at least six weeks postoperatively. EXCLUSION CRITERIA (excerpt) Prior-therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137). Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration (like neo-adjuvant androgen deprivation therapy (ADT), secondary hormone ablation or taxan-based chemotherapy). Distant metastases or suspicious lymph nodes outside the lower pelvis in imaging with PSMA PET-CT (patients with PET positive bone lesions that are morphologically not clearly suspicious of metastases and would not change clinical practice can be included). Clinical trial information: NCT04931979.

Development and validation of a quantitative reactive stroma biomarker (qRS) for prostate cancer prognosis

To develop and validate a new tissue-based biomarker that improves prediction of outcomes in localized prostate cancer by quantifying the host response to tumor. We use digital image analysis and machine learning to develop a biomarker of the prostate stroma called quantitative reactive stroma (qRS). qRS is a measure of percentage tumor area with a distinct, reactive stromal architecture. Kaplan Meier analysis was used to determine survival in a large retrospective cohort of radical prostatectomy samples. qRS was validated in two additional, distinct cohorts that include international cases and tissue from both radical prostatectomy and biopsy specimens. In the developmental cohort (Baylor College of Medicine, n=482), patients whose tumor had qRS > 34% had increased risk of prostate cancer-specific death (HR 2.94; p=0.039). This result was replicated in two validation cohorts, where patients with qRS > 34% had increased risk of prostate cancer-specific death (MEDVAMC; n=332; HR 2.64; p=0.02) and also biochemical recurrence (Canary; n=988; HR 1.51; p=0.001). By multivariate analysis, these associations were shown to hold independent predictive value when compared to currently used clinicopathologic factors including Gleason score and PSA. qRS is a new, validated biomarker that predicts prostate cancer death and biochemical recurrence across three distinct cohorts. It measures host-response rather than tumor-based characteristics, and provides information not represented by standard prognostic measurements.

Alternative prostate cancer grading systems incorporating percent pattern 4/5 (IQ-Gleason) and cribriform architecture (cGrade) improve prediction of outcome after radical prostatectomy

Percentage Gleason pattern 4, invasive cribriform and/or intraductal carcinoma (IC/IDC) and minor pattern 5 are recognized as independent parameters for prostate cancer outcome, but are not incorporated in current grade groups (GGs). Two proof-of-principle studies have proposed alternative grading schemes based on percentage Gleason pattern 4/5 (integrated quantitative Gleason score; IQ-Gleason) and IC/IDC presence (cribriform grade; cGrade). Our objective was to compare the performance of GG, IQ-Gleason and cGrade for predicting biochemical recurrence and metastasis after radical prostatectomy (RP). RP specimens of 1064 patients were pathologically reviewed and graded according to the three schemes. Discriminative power for prediction of biochemical recurrence-free (BCRFS) and metastasis-free (MFS) survival was compared using Harrell’s c-index. The GG distribution at RP was 207 (19.4%) GG1, 472 (44.4%) GG2, 126 (11.8%) GG3, 140 (13.2%) GG4 and 119 (11.2%) GG5. Grading according to 5-tier IQ-Gleason and cGrade systems led to categorical shifts in 49.8% and 29.7% of cases, respectively. Continuous IQ-Gleason had the best performance for predicting BCRFS (c-index 0.743, 95% confidence interval (CI) 0.715–0.771), followed by cGrade (c-index 0.738, 95%CI 0.712–0.759), 5-tier categorical IQ-Gleason (c-index 0.723, 95%CI 0.695–0.750) and GG (c-index 0.718, 95%CI 0.691–0.744). Continuous IQ-Gleason (c-index 0.834, 95%CI 0.802–0.863) and cGrade (c-index 0.834, 95%CI 0.808–0.866) both had better predictive value for MFS than categorical IQ-Gleason (c-index 0.823, 95%CI 0.788–0.857) and GG (c-index 0.806, 95%CI 0.777–0.839). In conclusion, the performance of prostate cancer grading can be improved by alternative grading schemes incorporating percent Gleason pattern 4/5 and IC/IDC.

Outcomes of Salvage Lymph Node Dissection in Oligorecurrent Prostate Cancer Post Radical Prostatectomy: Experience of an Oncologic Center in Spain

Introduction and ObjectivesWe report our experience with salvage lymph node dissection (sLND) in oligorecurrent prostate cancer (PCa) post radical prostatectomy (RP).Material and MethodsWe retrospectively analyzed data of 24 patients who underwent sLND for biochemical recurrence (BCR) post RP, from July 2012 to February 2018. sLND was performed following an extended bilateral template. Clinical and pathological characteristics of primary RP and sLND were reported. Biochemical response and initiation of additional therapy post sLND were analyzed. Survival analysis was performed using KaplanMeier curves.Results24 sLND were performed. RP specimens showed 58.3% of Gleason score 7 and 50% of locally advanced disease. Median time to BCR post RP was 24 months with a median PSA value of 1.4 ng/ml pre sLND. 75% of patients underwent imaging prior to sLND. sLND showed oligometastasis on the final pathology report in 54.2% of patients. Metastatic lymph nodes were mainly identified in the iliac artery territory (61.5%). Complete biochemical response (PSA < 0.2 ng/ml) was maintained throughout the first 12 months of follow-up in 20.83% of patients and 8.33% of patients at the end of the study (median follow-up 70 months). Survival rates free of additional therapy (ADT/RT) were 45.83% at one year and 25% at 5 years.ConclusionsWe observed a biochemical response post sLND in 20.83% of our patients, lasting throughout the first year of follow up, with survival rates free of ADT and/or RT of 45.83% at one year and 25% at 5 years.

A0316 - Results of in vivo focal transperineal laser ablation treatment for prostate cancer: Correlation of mpMRI and CEUS imaging to histology in radical prostatectomy specimen

A0316 - Results of in vivo focal transperineal laser ablation treatment for prostate cancer: Correlation of mpMRI and CEUS imaging to histology in radical prostatectomy specimen

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin.

BackgroundDuctal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized.ObjectiveTo investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers.Design, Setting, and ParticipantsIn 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis.ResultsIn 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2‐ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549−BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden.ConclusionsDuctal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.

Diagnosis and Localization of Prostate Cancer via Automated Multiparametric MRI Equipped with Artificial Intelligence

Prostate MRI scans for pre-biopsied patients are important. However, fewer radiologists are available for MRI diagnoses, which requires multi-sequential interpretations of multi-slice images. To reduce such a burden, artificial intelligence (AI)-based, computer-aided diagnosis is expected to be a critical technology. We present an AI-based method for pinpointing prostate cancer location and determining tumor morphology using multiparametric MRI. The study enrolled 15 patients who underwent radical prostatectomy between April 2008 and August 2017 at our institution. We labeled the cancer area on the peripheral zone on MR images, comparing MRI with histopathological mapping of radical prostatectomy specimens. Likelihood maps were drawn, and tumors were divided into morphologically distinct regions using the superpixel method. Likelihood maps consisted of pixels, which utilize the cancer likelihood value computed from the T2-weighted, apparent diffusion coefficient, and diffusion-weighted MRI-based texture features. Cancer location was determined based on the likelihood maps. We evaluated the diagnostic performance by the area under the receiver operating characteristic (ROC) curve according to the Chi-square test. The area under the ROC curve was 0.985. Sensitivity and specificity for our approach were 0.875 and 0.961 (p < 0.01), respectively. Our AI-based procedures were successfully applied to automated prostate cancer localization and shape estimation using multiparametric MRI.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy: Involvement of Single Versus Multiple Sextant Sites.

Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.

The Values of Systemic Immune-Inflammation Index and Neutrophil-Lymphocyte Ratio in the Localized Prostate Cancer and Benign Prostate Hyperplasia: A Retrospective Clinical Study.

PurposeTo evaluate the diagnostic values of systemic immune-inflammation index (SII) and neutrophil–lymphocyte ratio (NLR) in patients with localized prostate cancer (PCa).MethodsBetween January 2014 and December 2019, 117 patients with benign prostate hyperplasia (BPH) and 278 patients with localized PCa who underwent radical prostatectomy (RP) were included in this study. The inflammatory markers including SII, NLR, platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), lymphocyte ratio (LR), neutrophil ratio (NR), mean platelet volume (MPV), and red cell distribution (RDW) of these two groups were examined and analyzed. ROC curve analysis was performed to assess the discriminative ability of inflammatory markers and their combination with tPSA for PCa. The binary logistic regression model was used to evaluate the association between significant inflammatory markers and risk of PCa.ResultsThe pathological results from RP specimen comprised 72 (25.90%) patients with pT1, 168 (60.43%) patients with pT2, and 38 (13.67%) patients with pT3. According to Student’s t test, patients with PCa had higher NLR (p = 0.034), SII (p = 0.008), and NR (p = 0.004), and lower LR (p = 0.025), MPV (p = 0.003), and TPV (p = 0.022) compared with patients with BPH; the distribution of age, PLR, LMR, RDW, f/t PSA ratio, and BMI did not show any significant differences. The AUC for NLR, SII, NR, and tPSA was 0.697 (p = 0.015), 0.719 (p < 0.001), 0.647 (p = 0.009), and 0.708 (p < 0.001), with threshold values of 1.6, 471.86, 65.15%, and 12.89 ng/ml, respectively. Patients were divided into two groups according to the threshold values, respectively. By using the multivariable logistic regression models, NLR ≥ 1.6 (OR, 2.731; 95% CI, 0.937–7.961, p = 0.042), SII ≥ 471.86 (OR, 1.274; 95% CI 0.473–3.433; p = 0.033), and PSA ≥ 12.89 ng/ml (OR, 1.443; 95% CI, 0.628–3.944; p = 0.014) were independent risk factors associated with PCa. The AUC for combination of NLR, SII, and NR with tPSA was 0.705 (p < 0.001), 0.725 (p < 0.001), and 0.704 (p < 0.001), respectively.ConclusionThis study demonstrated that SII, NLR, and NR were all independent risk factors of PCa. These factors alone could provide better screen methods for PCa before biopsy. In addition, SII is a more powerful tool among these three inflammatory markers associated with PCa. Besides, combination of SII and NLR with tPSA had not much advantage compared with themselves alone.

The Influence of the Intraductal Carcinoma of the Prostate on the Short-Term Oncological Outcomes.

The presence of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens correlates with adverse prognostic factors such as worse biochemical recurrence-free survival, higher grade and stage disease. This study aimed to investigate the effect of IDC-P in radical prostatectomy specimens on short-term oncological outcomes. Patients who underwent RP at our clinic for prostate cancer between May 2016 and November 2019 were included in the study. They were divided into two groups based on the presence of IDC-P in RP specimens. Their clinical, pathological, and oncologic data were evaluated retrospectively. A total of 98 patients underwent RP with a mean age of 65.5 years (50-83) and a mean follow-up time of 31.2 months (6-52). Seventy and 28 patients were evaluated in the group without IDC-P and group with IDC-P, respectively. Surgical margin positivity (p=0.307) and lymph node metastasis (p=0.017) rates were higher in the group with IDC-P. Although there were no statistical differences between the groups, at follow-up biochemical recurrence rate (p=0.052) was higher, and mean time to biochemical recurrence rates were lower (p=0.057) in the group with IDC-P. The group with IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality to the group without IDC-P (p=0.037). Patients with IDC-P at RP specimens have more advanced disease, shorter biochemical recurrence-free, and cancerspecific survival than those without IDC-P. Defining the presence of IDC-P in RP specimens is critical in choosing the appropriate treatment strategy and predicting the prognosis.

Association of MyProstateScore (MPS) with prostate cancer grade in the radical prostatectomy specimen.

To evaluate the association between urinary MyProstateScore (MPS) and pathologic grade group (GG) at surgery in men diagnosed with GG1 prostate cancer (PCa) on biopsy. Using an institutional biospecimen protocol, we identified men with GG1 PCa on biopsy and PSA ≤10 ng/ml who underwent radical prostatectomy (RP) at the University of Michigan. MPS was retrospectively calculated using prospectively collected, post-DRE urine samples. The primary outcome was upgrading on RP pathology, defined as GG ≥ 2. The associations of MPS, PSA, and PSA density (PSAD) with upgrading were assessed on univariable logistic regression, and the predictive accuracy of each marker was estimated by the area under the receiver operating characteristic curve (AUC). There were 52 men with urinary specimens available that met study criteria, based on biopsy Gleason Grade and specimen collection. At RP, 17 men (33%) had GG1 cancer and 35 (67%) had GG ≥ 2 cancer. Preoperative MPS was significantly higher in patients with GG ≥ 2 cancer at surgery (median 37.8 [IQR, 22.2-52.4]) as compared to GG1 (19.3 [IQR, 9.2-29.4]; P = 0.001). On univariable logistic regression, increasing MPS values were significantly associated with upgrading (odds ratio 1.07 per one-unit MPS increase, 95% confidence interval 1.02-1.12, P = 0.004), while PSA and PSAD were not significantly associated with upgrading. Similarly, the discriminative ability of the MPS model (AUC 0.78) for upgrading at RP was higher compared to models based on PSA (AUC 0.52) and PSAD (AUC 0.62). In men diagnosed with GG1 PCa who underwent surgery, MPS was significantly associated with RP cancer grade. In this limited cohort of men, these findings suggest that MPS could help identify patients with undetected high-grade cancer. Additional studies are needed to better characterize this association.

Comparison of 12-Core Prostate Biopsy Results with Corresponding Radical Prostatectomy Specimens

Comparison of 12-Core Prostate Biopsy Results with Corresponding Radical Prostatectomy Specimens

Raised prostate-specific antigen alone may not be a true predictor in high-risk prostate cancer: A retrospective cohort analysis.

Introduction:Prostate-specific antigen (PSA) >20 ng/mL in isolation is a criterion for classification as “high-risk” prostate cancer (PCa). However, among Indian men, PSA elevation is often seen even in the absence of PCa and patients with PSA as the sole criterion for the high-risk disease may have different outcomes from those categorized as high risk due to adverse pathological features. We compared the operative, oncological, and functional outcomes after robot-assisted radical prostatectomy (RARP) in men with high-risk PCa categorized using PSA alone versus clinical and histopathological findings.Materials and Methods:In an Institute Review Board-approved study, men undergoing RARP with high-risk PCa with at least 2-year follow-up were categorized into those with PSA >20 ng/ml being the sole criteria for being high risk (Group A) versus those with Gleason score ≥8 or ≥T2c disease but any PSA level (Group B). The two groups were compared for perioperative, oncological, and functional outcomes.Results:Fifty-three patients with high-risk disease were included. Twenty-six patients (48.9%) were classified into Group A while 27 patients (50.9%) were classified into Group B. The median PSA was significantly higher in Group A (31 [26–35] ng/ml in Group A vs. 21 [12–34] ng/ml in Group B, P = 0.006) and on histopathology of radical prostatectomy specimen, 24 (92.3%) patients had GG ≤3 disease in Group A versus 10 (37%) patients in Group B (P < 0.001). Patients in both the groups had similar perioperative and continence outcomes. However, Group A had significantly lower biochemical recurrence rate (3/26 [11.5%]) as compared to Group B (11/27 [40.7%]) (P = 0.012).Conclusions:PSA >20 ng/ml is the single most common criterion for stratification as high-risk PCa. However, men with PSA >20 ng/ml in isolation, without another adverse criterion, have better outcomes than men with adverse clinical or pathological criteria for high-risk disease.

Localized Amyloidosis of the Seminal Tract is not Associated With Subsequent Development of Systemic Amyloidosis

ObjectiveTo investigate if localized amyloidosis of the seminal tract (LAST) is associated with subsequent development of systemic amyloidosis. Prior reports recorded no systemic amyloidosis at the time of LAST diagnosis. However, no follow-up studies exist to confirm that LAST is not a risk factor for subsequent development of systemic amyloidosis. MethodsOur study cohort included patients whose prostate biopsy (PB) or radical prostatectomy (RP) specimen demonstrated LAST between 2014–2021. Clinical variables including age, race/ethnicity, prostate specific antigen (PSA), and prostate weight were analyzed. Patients were assessed for clinical and laboratory evidence of systemic amyloidosis and lymphoproliferative conditions during the follow-up period. ResultsThirty-six men (26 RPs, 9 PBs, and 1 cystoprostatectomy) had LAST. Our study cohort included 18 white Hispanic, 9 white non-Hispanic, 7 black, and 1 Asian men. Median age was 67 years, mean PSA was 9.8 ng/mL. Over a median follow-up period of 20 months (mean, 30) in 27 men, none developed systemic amyloidosis. Frequency of LAST in RP specimens was 1.2% (26/2,135) and corelated with age (67 vs 63 years, P-value = .004). Race/ethnicity, PSA, and prostate weight were not associated with the incidence of LAST. ConclusionsLAST is not a harbinger of systemic disease. The incidence of LAST in a contemporary RP cohort is significantly lower than in previously published studies. While patient age positively corelates with LAST, PSA and prostate weight are not associated with the condition. There is no difference in the frequency of LAST between white Hispanic, white non-Hispanic, and black men.

Radical or Not-So-Radical Prostatectomy: Do Surgical Margins Matter?

Simple SummaryProstate cancer is the second most common noncutaneous malignancy in men. Prostatectomy is a commonly used treatment modality for selected patients. The prostate’s ill-defined borders and its vicinity with vital structures complicate the wide excision of the organ, resulting in positive margins of resection. Neoplastic infiltration of margins of resection in prostatectomy specimens affects patients’ prognosis. The surgical technique and surgeons’ expertise affect the incidence of margin positivity. The location and the extent of positive margins diversify the risk of recurrence, with basal infiltration and multifocal foci of positive margins behaving more aggressively. Pathologists are encouraged to thoroughly report the status of margins of resection, as they provide important information for patients’ prognosis and enable the clinician to decide upon the most appropriate subsequent therapeutic steps.Prostate cancer is the second most common malignancy in men, and prostatectomy is the treatment of choice for most patients with at least low risk of progression. The presence of positive margins in the radical prostatectomy specimen is considered an adverse pathologic feature, and may prompt additional therapeutic intervention in the patients. The absence of a distinct capsule around the prostate and intraoperative manipulations that aim to minimize postoperative adverse effects, complicate its wide removal. Proper handling of the specimen during the gross processing is essential for accurate determination of the status of margins or resection. Positive margins, defined as the presence of neoplastic glands in the highlighted-with-ink margin of resection, range from 6–38%. The surgical technique, surgeon’s expertise and tumor (i.e., grade and stage) and patients’ (i.e., BMI) characteristics affect the rate of margin positivity. Extensive or multifocal and nonanterior/nonapical positive margins are linked with higher recurrence rates, especially in organ-confined disease, underscoring the need for treating these patients more aggressively. In summary, detailed description of the status of the margins should be performed in every pathology report to determine patients’ prognosis and the most appropriate therapeutic plan.

Cribriform architecture outperforms Gleason pattern 4 percentage and tertiary Gleason pattern 5 in predicting the outcome of Grade Group 2 prostate cancer patients.

AimsGleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence‐free survival (BCRFS).Methods and resultsOf 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with ≥25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P < 0.001) and TP5 (20.6% versus 5.8%; P < 0.001) than those with <25% GP4. In unadjusted analysis, an increased GP4 percentage [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.0–1.6; P = 0.04] and IC/IDC (log rank P < 0.001) were associated with shorter BCRFS, whereas TP5 (P = 0.12) and a dichotomised (<25%, ≥25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2–2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors.ConclusionIn conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports.

Identification of Morphologic Criteria Associated with Biochemical Recurrence in Intraductal Carcinoma of the Prostate.

Simple SummaryDespite the strong association of the aggressive intraductal carcinoma of the prostate (IDC-P) with an increased risk of biochemical recurrence (BCR), around 40% of men remain BCR-free five years post-surgery. In this retrospective study, we aimed to evaluate the prognostic value of several morphological criteria of IDC-P using BCR as the endpoint. In multivariate analysis (validation cohort, n = 69), the presence of cells with irregular nuclear contours (CINC) or blood vessels was independently associated with an increased risk of BCR (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.09–4.96, p = 0.029). Furthermore, when combining the criteria, the presence of any CINC, blood vessels, high mitotic score, or comedonecrosis showed a stronger association with BCR (HR 2.74, 95% CI 1.21–6.19, p = 0.015). Provided that our findings are validated in larger cohorts, evaluation of morphologic features of IDC-P could serve as a risk stratification tool for patients with IDC-P.Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer strongly associated with an increased risk of biochemical recurrence (BCR). However, approximately 40% of men with IDC-P remain BCR-free five years after radical prostatectomy. In this retrospective multicenter study, we aimed to identify histologic criteria associated with BCR for IDC-P lesions. A total of 108 first-line radical prostatectomy specimens were reviewed. In our test cohort (n = 39), presence of larger duct size (>573 µm in diameter), cells with irregular nuclear contours (CINC) (≥5 CINC in two distinct high-power fields), high mitotic score (>1.81 mitoses/mm2), blood vessels, and comedonecrosis were associated with early BCR (<18 months) (p < 0.05). In our validation cohort (n = 69), the presence of CINC or blood vessels was independently associated with an increased risk of BCR (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.09–4.96, p = 0.029). When combining the criteria, the presence of any CINC, blood vessels, high mitotic score, or comedonecrosis showed a stronger association with BCR (HR 2.74, 95% CI 1.21–6.19, p = 0.015). Our results suggest that IDC-P can be classified as low versus high-risk of BCR. The defined morphologic criteria can be easily assessed and should be integrated for clinical application following validation in larger cohorts.

PTEN Loss and PD-L1 Expression of Different Histological Patterns of Prostate Cancer

AimsAlthough several studies have evaluated PTEN loss in Prostatic Adenocarcinoma (PCa), PTEN loss correlation with different histological patterns only has a few studies. Although several studies have evaluated PD-L1 expression in PCa and its correlation with Gleason scores, as far as we know, there are no prior studies that have included a comparison between PD-L1 expression and histological patterns of PCa. This study aims to evaluate PTEN loss and PD-L1 expression by immunohistochemistry in different histological patterns of PCa. MethodsThe current study included consecutive 98 radical prostatectomy specimens with 151 foci with different Gleason Grade (GG) patterns. ResultsThe highest frequency of PTEN loss was observed in GG4 cribriform and glomeruloid patterns (59.3%, p < 0.001). Combined score (CS) PD-L1 positivity was observed in fourteen patients (14.2%). Tumor cell (TC) and tumor-associated inflammatory cells (IC) PD-L1 positivity was observed in 10 (10.2%) and 7 (7.1%) patients. The highest frequency of PD-L1 expression was observed in the GG5 pattern, and between GG4 patterns, the irregular pattern had the highest PD-L1 positivity. ConclusionsIn conclusion, in our cohort of consecutive unselected cases of prostatic carcinoma, we observed the highest PTEN loss rate in the GG4 cribriform and glomeruloid pattern and the highest PD-L1 expression rate in the GG5 and GG4 irregular patterns. These results may predict molecular differences between different histological patterns in PCa and may be used to inform a treatment decision. Future studies should investigate these differences between histological patterns of PCa to predict response to immunotherapy in larger cohorts.