Tertiary Gleason Pattern Research Articles

Enhancing Prostate Cancer Diagnosis: Artificial Intelligence–Driven Virtual Biopsy for Optimal Magnetic Resonance Imaging-Targeted Biopsy Approach and Gleason Grading Strategy

An optimal approach to magnetic resonance imaging fusion targeted prostate biopsy (PBx) remains unclear (number of cores, intercore distance, Gleason grading [GG] principle). The aim of this study was to develop a precise pixel-wise segmentation diagnostic artificial intelligence (AI) algorithm for tumor detection and GG as well as an algorithm for virtual prostate biopsy that are used together to systematically investigate and find an optimal approach to targeted PBx. Pixel-wise AI algorithms for tumor detection and GG were developed using a high-quality, manually annotated data set (slides n = 442) after fast-track annotation transfer into segmentation style. To this end, a virtual biopsy algorithm was developed that can perform random biopsies from tumor regions in whole-mount whole-slide images with predefined parameters. A cohort of 115 radical prostatectomy (RP) patient cases with clinically significant, magnetic resonance imaging-visible tumors (n = 121) was used for systematic studies of the optimal biopsy approach. Three expert genitourinary (GU) pathologists (Y.T., A.P., A.Q.) participated in the validation. The tumor detection algorithm (aware version sensitivity/specificity 0.99/0.90, balanced version 0.97/0.97) and GG algorithm (quadratic kappa range vs pathologists 0.77-0.78) perform on par with expert GU pathologists. In total, 65,340 virtual biopsies were performed to study different biopsy approaches with the following results: (1) 4 biopsy cores is the optimal number for a targeted PBx, (2) cumulative GG strategy is superior to using maximal Gleason score for single cores, (3) controlling for minimal intercore distance does not improve the predictive accuracy for the RP Gleason score, (4) using tertiary Gleason pattern principle (for AI tool) in cumulative GG strategy might allow better predictions of final RP Gleason score. The AI algorithm (based on cumulative GG strategy) predicted the RP Gleason score of the tumor better than 2 of the 3 expert GU pathologists. In this study, using an original approach of virtual prostate biopsy on the real cohort of patient cases, we find the optimal approach to the biopsy procedure and the subsequent GG of a targeted PBx. We publicly release 2 large data sets with associated expert pathologists’ GG and our virtual biopsy algorithm.

Effect of Adjuvant Chemotherapy in Highly Malignant Non-Metastatic Prostate Cancer: An Interim Analysis of Non-Randomized Comparative Trials.

Gleason grade group 5 (GG5) prostate cancers is aggressive with high metastatic rates and is not sensitive to androgen deprivation therapy (ADT). Even the presence of a limited (tertiary) Gleason pattern 5 component may have high aggressive biological behavior. This study aims to prospectively evaluate whether a non-androgen receptor pathway therapy - adjuvant chemotherapy could improve clinical outcomes among non-metastatic prostate cancer with the above highly malignant characters. This prospective non-randomized clinical trial included non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or tertiary Gleason pattern 5. Each subject was allowed to decide whether to receive four to six cycles chemotherapy of docetaxel after receiving a standard treatment (i.e., radical surgery ± radiotherapy or radical radiotherapy combined with long-term ADT). The primary endpoint was event-free survival (EFS). Event was defined as any of biochemical failure or imaging failure, or change of systemic therapy due to PSA arises, or death. The secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. A total of 188 consecutive patients were enrolled from November 2019 to November 2022. Median prostate-specific antigen was 26.6 ng/ml. 52% had T3b to T4 disease, 27% had N1 disease. 140 patients received standard therapy only, and 48 patients received adjuvant chemotherapy after radical therapy. The median follow-up time was 18.4 (3.0-36.7) months. The estimated 36-month EFS of the chemotherapy group and the control group were 94.7% vs. 72.8% (p = 0.044). There were 1 event who added novel endocrine therapy in the chemotherapy group, and 21 events in the control group, including 6 cases of biochemical recurrence and 9 cases of lymph node and distant metastasis, 4 cases that changed systemic therapy and 2 cases died. The MFS of the two groups at 36 months were 100% and 90.7%, respectively (P = 0.143). After the 1:1 propensity score match, the EFS and MFS of the two groups were 94.7% and 80.8% (P = 0.069), and 100% and 93.1% (P = 0.132), respectively. The urinary toxicity of grade 2 and 3 in the chemotherapy group and the control group were 4.2% and 7.1% (P = 0.134) while the grade 2 rectal toxicity were 5.0% and 10.4% (P = 0.317), respectively. No grade 4 toxicity occurred. Considering the chemotherapy-related side effects, grade 3 or above toxicity were leukopenia (41.7%), alopecia (27.1%), thrombocytopenia (2.1%) and edema (2.1%). Results of this interim analysis shows that the addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall recurrence and metastasis free survival of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Prostate Pathology: What is New in the 2022 WHO Classification of Urinary and Male Genital Tumors?

In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male Genital Tumors, which provides a comprehensive update on tumor classification of the genitourinary system. This review article focuses on prostate carcinoma and underscores changes in the prostate chapter as well as those made across the entire series of the 5th edition of WHO Blue Books. Although no major alterations were made to this chapter, some of the most notable updates include restructure of contents and introduction of a new format; standardization of mitotic counts, genomic nomenclatures, and units of length; refined definition for the terms "variant", "subtype", and "histologic pattern"; reclassification of prostatic intraepithelial neoplasia (PIN)-like adenocarcinoma as a subtype of prostatic acinar adenocarcinoma; and recognition of treatment-related neuroendocrine prostatic carcinoma as a distinct tumor type. Evolving and unsettled issues related to grading of intraductal carcinoma of the prostate and reporting of tertiary Gleason pattern, the definition and prognostic significance of cribriform growth pattern, and molecular pathology of prostate cancer will also be covered in this review.

Tertiary Gleason Pattern 5 and a High Genomic Classifier Score Better Predicts Lymph Node Invasion at Radical Prostatectomy in 20,441 Intermediate-Risk Disease Patients

<h3>Purpose/Objective(s)</h3> The POP-RT and SSPORT trial showed that pelvic lymph node radiation therapy (PLNRT) can improve prostate or bed-only oncologic outcomes. Grade groups 2 (GG2) or 3 (GG3) and Tertiary Gleason pattern 5 (TP5) are heterogeneous patient groups with varied prognoses. Genomic classifiers (GC) may provide additional information essential to identifying optimal pelvic radiotherapy candidates. We hypothesized that TP5, and a GC, could improve prognostication of lymph node invasion (LNI) after radical prostatectomy (RP) over traditional clinicopathologic risk factors alone. <h3>Materials/Methods</h3> The Decipher GRID database (Veracyte, San Diego, CA) contains de-identified GC testing and pathology results for patients tested between November 2015 and March 2020. Intermediate risk patients with GG2 or GG3 were included in the analysis of continuous GC scores (range 0-1) and GC risk groups (low, intermediate, and high). Multivariable logistic regression (MVA) was used to quantify the relationship between LNI with GC, TP5, and other clinicopathologic features (age, race, extraprostatic extension, seminal vesicle invasion, bladder neck invasion). <h3>Results</h3> 20,441 patients were included (11,934 with GG2 (58.4%) and 8,507 (41.6%) with GG3 disease). Of those with GG2 and GG3 disease, 1,451 (12.2%) and 2,911 (34.2%) had TP5, respectively. Patients with TP5 had a significantly higher GC score (median [interquartile range (IQR)]: 0.39 [0.24-0.61] vs 0.53 [0.32-0.75], p<0.001 for GG2 and median [IQR]: 0.58 [0.35-0.81] vs 0.66 [0.43-0.86, p<0.001 for GG3. In MVA adjusted for clinicopathologic features, TP5 and higher GC score were independently associated with the presence of LNI in both GG2 (TP5: odds ratio [OR] 1.60, 95% CI 1.07-2.38, p=0.02 and GC: OR 1.20 per 0.1 increase, 95% CI 1.11-1.29, p<0.001) and GG3 (TP5: OR 1.47, 95% CI 1.16-1.87, p<0.01 and GC: OR 1.13 per 0.1 increase, 95% CI 1.07-1.19, p<0.001) patients. TP5 patients with GG2 or GG3 and high GC have a 3.8- and 1.8-fold risk of LNI over those with a low GC, respectively. Patients with GC high and GG2 or GG3 have a 2.7- and 1.8-fold risk of LNI over those with or without TP5, respectively (Table 1). <h3>Conclusion</h3> TP5 was associated with higher GC scores and adverse clinicopathologic features. TP5 and higher GC are independently associated with LNI while controlling for other clinicopathologic risk factors, demonstrating their importance in future studies of pelvic RT treatment intensification or de-intensification for these patients.

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.

Prognostic value of cribriform size, percentage, and intraductal carcinoma in Gleason score 7 prostate cancer with cribriform Gleason pattern 4

Cribriform Gleason pattern 4 (CGP4) is an indicator of poor prognosis in Gleason Score 7 prostate cancer; however, the significance of the size and percentage of this pattern and the presence of concomitant intraductal carcinoma (IDC) in these patients is unclear. To study the significance of these parameters in radical prostatectomy specimens, 165 cases with CGP4 were identified and reviewed (2017-2019). The size and percentage cribriform pattern and presence of IDC were noted and correlated with adverse pathological features and biochemical recurrence (BCR)-free survival. On review, 156 cases had CGP4 (Grade Group 2: 87 and Grade Group 3: 69). Large cribriform pattern and cribriform percentage of >20% showed significant association with extraprostatic extension, surgical margin positivity, and presence of IDC, whereas the presence of IDC was associated with all the analyzed adverse pathological features. BCR was seen in 22 of 111 (20%) patients after a median follow-up of 11 months, and of these, 21 had large cribriform pattern. On univariate analysis, all parameters had significant predictive values for BCR-free survival except for tertiary Gleason pattern 5. On multivariate analysis, while >20% cribriform pattern was trending to be an independent predictor, only lymphovascular invasion was statistically significant. Large cribriform pattern, >20% cribriform, and presence of IDC are additional pathologic parameters of potential value in identifying patients with high risk for early BCR.

Clinicopathological Analysis of the ISUP Grade Group And Other Parameters in Prostate Cancer: Elucidation of Mutual Impact of the Various Parameters.

BackgroundProstate cancer has become increasingly common worldwide. Although Grade group (GG) is widely accepted as an indicator of prostate cancer grade, there are malignancies that cannot be defined by GG alone. Moreover, the relationship between GG and other parameters remains unclear. Herein, we aimed to explore the biological characteristics of prostate cancer.MethodsThis study included 299 radical prostatectomy cases. The Chi-square test and analysis of variance were used to analyze the association of GG with binary and continuous variables. We then conducted morphological analyses. Multivariate analyses were performed to extract the data on risk factors for biochemical recurrence (BCR) and lymph node metastasis.ResultsThe lymphatic, venous, perineural, and seminal vesicle invasion rates were 37/299 (12.4%), 25/299 (8.4%), 280/299 (93.6%), and 23/299 (7.7%), respectively. The extraprostatic extension (EPE), positive surgical margin, tertiary Gleason pattern 5, intraductal carcinoma of the prostate gland, and lymph node metastasis rates were 89/299 (29.8%), 106/299 (35.5%), 33/260 (12.7%), 56/299 (18.7%), and 23/299 (7.7%), respectively. As GG increased, various parameters became easier to visualize; however, there were differences between the parameters. Postoperative BCR was observed in 31/242 (12.8%) cases without preoperative hormone therapy; GG2, GG3, GG4, and GG5 accounted for 4, 7, 7, and 13 cases, respectively. Multivariate analyses revealed that GG and tumor diameter were significant risk factors for early BCR, whereas lymphatic invasion, EPE, and seminal vesicle invasion were significant risk factors for lymph node metastasis. For BCR, the odds ratios (ORs) for GG and tumor diameter were 2.253 (95% confidence interval (CI]): 1.297–3.912; P=0.004) and 1.074 (95% CI: 1.011–1.142; P=0.022), respectively. For lymph node metastasis, ORs for the presence of lymphatic invasion, EPE, and seminal vesicle invasion were 7.425 (95% CI: 1.688–22.583; P=0.004), 4.391 (95% CI: 1.037–18.589; P=0.044), and 5.755 (95% CI: 1.308–25.316; P=0.021), respectively.ConclusionsWe summarized various parameters correlating with each GG. Through multivariate analyses, we established the independent risk factors for early BCR and lymph node metastasis. In addition to GG, other important indices of malignancy were determined and weighted to provide a basis for future investigations.

IJU this issue

This issue of International Journal of Urology contains one Review Article, 11 Original Articles, two Urological Notes and 13 Editorial Comments. Taguchi et al (Tokyo, Japan) reviewed the evidence on the prognostic significance of tertiary Gleason pattern (TGP), and discussed how to deal with it in the context of the contemporary Gleason score and Gleason grade grouping. According to the 2019 International Society of Urological Pathology, a provisional definition of TGP is “<5% Gleason pattern 4 or 5 in radical prostatectomy specimens.” Although no objective and scientific data supporting this cut-off value have been reported, TGP should be routinely reported in radical prostatectomy specimens and further studies are required to assess the associations of TGP with prognostic significances. In the Original Articles, Kimura et al. (Tottori, Japan) reported the impact of penile rehabilitation on the recovery of erectile function after robot-assisted radical prostatectomy. Erectile dysfunction still remains an important complication after robot-assisted radical prostatectomy despite the preservation of neurovascular bundles with nerve-sparing (NS) surgery. This study presents novel findings regarding postoperative penile rehabilitation with phosphodiesterase-5 inhibitor, not only in cases of bilateral NS and/or unilateral NS, but also in other types of NS, such as partial NS or non-NS. Zhang et al. (Beijing, China) evaluated the outcomes and the learning curves of flexible ureteroscopy (FURS) and mini-percutaneous nephrolithotomy for pediatric kidney stones larger than 2 cm. FURS has already been shown to be a safe and feasible procedure alternative to percutaneous nephrolithotomy for children with upper urinary stones with a systematic review and meta-analysis (Urolithiasis 2019; 47: 189–99); however, this study showed an interesting finding, that a minimum of 20 cases of mini-percutaneous nephrolithotomy and 50 cases of FURS are necessary to achieve a high stone-free rate for pediatric kidney stones larger than 2 cm. Okada et al. (Chiba, Japan) reported the differences in the handling of forceps between the one-surgeon and two-surgeon techniques using an off-site simulator model. Nearly half of endourologists used only the dusting technique in their FURS practice, according to a recent worldwide survey of FURS practice from the European Association of Urology sections of young academic urologists (aged <40 years) and uro-technology groups (Cent. Eur. J. Urol. 2019; 72: 393–7). The European Association of Urology Guidelines on Urolithiasis has mentioned that “dust and go” strategies should be limited to the treatment of large (renal) stones and stones that can be extracted by endoscopic forceps or baskets. Therefore, the establishment of standards, safety requirements and acceptable procedures for basketing is essential. A large-scale study is required to confirm its usefulness as a new standard modality of stone retrieval in FURS. Shobeirian et al. (Rasht, Iran) evaluated the efficacy of intraprostatic injection of prophylactic antibiotics for the prevention of infections after transrectal ultrasonography-guided prostate biopsy. This unique concept of injecting antibiotics directly into the prostate was proposed in both animal and human studies, and its efficacy in the treatment of drug-resistant chronic prostatitis has already been reported. It will be necessary to carry out a randomized controlled trial. In the Urological Notes, Tully et al. (Boston, USA) analyzed bladder cancer incidence trends using the Surveillance, Epidemiology and End Results database, with a focus on distant stage among young individuals. They discussed possible explanations for the rising incidence of distant bladder cancer among young individuals. Unfortunately, the limited space does not allow me to introduce all the articles. However, all the papers are very interesting and informative. Please enjoy this issue of International Journal of Urology. None declared.

Narrative review of prostate cancer grading systems: will the Gleason scores be replaced by the Grade Groups?

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.

Prognostic significance of tertiary Gleason pattern in the contemporary era of Gleason grade grouping: A narrative review.

Since the Gleason score was developed in 1966 as a histological classification for prostate cancer, it has been widely used in clinical practice and has evolved over time. The concept of a "tertiary Gleason pattern" (also known as a minor Gleason pattern) was first proposed in 2000, and has been used in clinical practice since the 2005 International Society of Urological Pathology conference. The prognostic significance of a tertiary Gleason pattern has been widely validated in various settings of prostate cancer, whereas its definition has yet to be fully established. Currently, a provisional definition of tertiary Gleason pattern is "<5% Gleason pattern 4 or 5 in radical prostatectomy specimens." In contrast, "Gleason grade grouping" was proposed in 2013 and came into use in clinical practice in 2016 according to the 2014 International Society of Urological Pathology conference. Although the prognostic significance of Gleason grade grouping has already been widely confirmed, it does not incorporate the concept of tertiary Gleason pattern. Recently, the 2019 International Society of Urological Pathology conference discussed how to handle tertiary Gleason pattern in the current Gleason scoring system, but no consensus was reached on the issue. This review summarizes the evidence on the prognostic significance of tertiary Gleason pattern and discusses how to deal with it in the context of the contemporary Gleason grade grouping. It also refers to reporting of the percentage of Gleason patterns 4 and 5, as well as quantitative Gleason score models incorporating tertiary Gleason pattern.

Quantification of the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy: development of the modified Gleason grade grouping (mGGG) model

BackgroundWhile the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has “quantified” the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy.MethodsWe reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed.ResultsDuring a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P < 0.05). In the robustness analysis, the c-index for salvage treatment-free survival was also significantly improved from 0.619 of the original GGG model to 0.638 of the mGGG model (P < 0.05).ConclusionsThe quantitative risk of tertiary (< 5%) Gleason pattern 5 is slightly higher than that of secondary (5–50%) Gleason pattern 4. Our newly developed mGGG model more accurately predicts outcomes after radical prostatectomy than the original GGG model.

Prostate Carcinoma Grade and Length But Not Cribriform Architecture at Positive Surgical Margins Are Predictive for Biochemical Recurrence After Radical Prostatectomy.

Postoperative biochemical recurrence occurs in up to 40% of prostate carcinoma patients treated with radical prostatectomy. Primary tumor grade and cribriform architecture are important parameters for clinical outcome; however, their relevance at positive surgical margins has not been completely elucidated yet. We reviewed 835 radical prostatectomy specimens and recorded pT-stage, surgical margin status, Grade Group, and cribriform architecture of the primary tumor and at positive surgical margins. Clinicopathologic parameters and biochemical recurrence-free survival (BCRFS) were used as endpoints. Positive surgical margins were present in 284 (34%) patients, with a median cumulative length of 5.0 mm. In 46%, the Grade Group at the margin was equal to the primary tumor grade, while being lower in 42% and higher in 12%. In multivariable analysis, Grade Group at the margin outperformed the Grade Group of the primary tumor in predicting BCRFS. Among primary Grade Group 2 patients, 56% had Grade Group 1 disease at the margin. Multivariable analysis identified cumulative length, Grade Group at the margin, and lymph node metastasis as independent predictors for BCRFS, while percentage Gleason pattern 4, tertiary Gleason pattern 5 of the primary tumor, and cribriform architecture at the margin were not. In conclusion, the Grade Group at the positive surgical margin was dissimilar to the primary tumor grade in 54% and better predicted BCRFS than the primary tumor grade. Cumulative length and tumor grade at the margin were independent predictors for BCRFS, whereas cribriform architecture at the margin was not.

Significance of tertiary Gleason pattern 5 in patients with Gleason score 7 after radical prostatectomy: a retrospective cohort study.

PurposeTo evaluate the association between tertiary Gleason pattern 5 (TGP5) and biochemical recurrence (BCR) in patients with prostate cancer (PCa) with a Gleason score (GS) of 7 after radical prostatectomy (RP).Patients and methodsThis retrospective study identified 350 patients who received RP and were graded as GS 7 (3+4 or 4+3) at the West China Hospital from January 2009 to December 2017. Initially, the patients were divided into two groups, TGP5 absence and TGP5 presence, independent of Gleason score. We further stratified the patients by adding the Gleason score into four groups: GS 3+4, GS 3+4/TGP5, GS 4+3, and GS 4+3/TGP5. Cox proportional-hazards models were used to evaluate the association between the status of TGP5 and BCR after adjusting for the confounding factors.ResultsThe risk of BCR was significantly higher in patients with TGP5 when compared to patients without TGP5 (P=0.04, HR=2.17 95%, Cl: 1.03–4.59). For patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3 (P=0.04, HR=2.45, 95% Cl: 1.04–5.76).ConclusionThe TGP5 in patients with GS 7 had strong association with the risk of BCR and was an independent predictor for BCR. Further research on larger data sets is needed to confirm these findings.

Predicting biochemical recurrence after radical prostatectomy: the role of prognostic grade group and index tumor nodule

The aim of the current study was to test whether the grade group assessed in the index tumor nodule predicts biochemical recurrence after surgery. The study cohort series included 144 consecutive patients treated by laparoscopic radical prostatectomy. The following parameters were evaluated in each case: type of radical prostatectomy (with/without lymphadenectomy), pT and pN status, histologic type of prostate carcinoma (acinar versus mixed histology), surgical margin resection status, perineural invasion, lymphovascular invasion, biochemical recurrence status, presence of tertiary Gleason 5 pattern, and grade group that was assessed both in overall prostate cancer and in index (dominant) tumor nodule. Twenty patients (13.9%) experienced postoperative biochemical recurrence at a mean follow-up time of 12.2 months. The univariate survival analysis selected type of radical prostatectomy, histological subtype, lymphovascular invasion, American Joint Committee on Cancer pT and pN classification, tertiary Gleason 5 pattern, preoperative serum prostate specific antigen level, and the grade group assessed in both the overall prostate and index tumor nodule as significant for biochemical recurrence-free survival. Type of radical prostatectomy (P = .020), histological subtype (P = .002), lymphovascular invasion (P = .023), tertiary Gleason pattern 5 (P = .016), and grade group classification in index tumor nodule (P ≤ .0001) were selected as independent predictors of biochemical recurrence-free survival. In conclusion, our results validate grade group in the index tumor nodule as an independent predictor of biochemical recurrence-free survival, thus emphasizing the value of reporting grade group in index tumor nodule. The main limitation of our study is the relatively low number of cases in the current series, suggesting the need of large confirmatory studies.

The validation of the 2014 International Society of Urological Pathology (ISUP) grading system for patients with high-risk prostate cancer: a single-center retrospective study.

IntroductionSince the new 2014 grading system was recommended by the International Society of Urological Pathology (ISUP), it has been validated in patients with localized prostate cancer (PCa) and it has shown excellent prognostic value. However, its predictive power in high-risk PCa remains unclear.MethodsA total of 420 patients with high-risk PCa who underwent radical prostatectomy (RP) were included in this study. Biochemical recurrence-free survival (BRFS) was set as the endpoint.ResultsBiochemical recurrence occurred in 84/420 (20.0%) patients at the end of follow-up. Compared to the three-tier grouping system, the five-tier grouping system could more effectively distinguish the BRFS of patients with higher predictive accuracy (C-index: 0.599 vs 0.646). The BRFS of patients with grade group (GG) 1 and GG 2 was similar (P=0.593). Also, the prognosis between those with GG 2 and GG 3 could be clearly distinguished (P=0.001). However, the discrimination capacity between patients with GG 3 and GG 4 was limited (P=0.681). When tertiary Gleason pattern (TGP5) and intraductal carcinoma of the prostate (IDC-P) were excluded, the HR value of the GG 4 group vs the GG 3 group increased from 1.15 (95% CI: 0.59–2.22) to 1.49 (95% CI: 0.72–3.10) and 1.36 (95% CI:0.65–2.83), respectively.ConclusionsThis study is the first to validate the new 2014 ISUP grading system in patients with high-risk PCa who underwent RP. The 2014 system could effectively classify patients into five groups with high predictive accuracy. Notably, the existence of TGP5 and IDC-P needs to be routinely reported in clinical practice, which could help to support the predictive value of the new grading system.

Significance of tertiary pattern 5 in patients with gleason score 7 after radical prostatectomy.

117 Background: To evaluate the association between tertiary Gleason pattern (TGP) 5 and the biochemical recurrence (BCR) in patients with prostate cancer (PCa) of Gleason score (GS) 7 after radical prostatectomy(RP). Methods: This retrospective study collected 387 patients received RP and diagnosed GS 7 (3+4 or 4+3) in the West China Hospital from January 2009 to December 2017.Regardlessly the first Gleason pattern, patients were divide into 2 groups: TGP5 absence and TGP5 presence. Furthermore, we added the primary Gleason pattern to divided patients into 4 groups: GS 3+4, GS 3+4/TGP 5, Gleason 4+3, Gleason 4+3/TGP 5. Cox proportional-hazards models was used to evaluate the association between the status of TGP5 and BCR after adjusting the confounding factors with follow-up time as the underlying time scale. All the analyses were conducted with the use of statistical software packages Rnand EmpowerStats and conducted as two sides and P values less than 0.05 were considered statistical significance. Results: In the results by using Cox proportional-hazards model, regardless the primary Gleason pattern, comparing TGP5 absence (89.7%) and presence (10.3%), the risk of BCR for patients with tertiary Gleason pattern 5 presence was statistically significantly higher than absence (P = 0.02, HR = 2.24, 95%Cl: 1.12-4.49). In terms of the patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3.(P = 0.02, HR = 2.56, 95%Cl: 1.16-5.67). There was a marked trend that patients with Gleason 3+4/TGP 5 has a higher risk of BCR compared with patients with Gleason 3+4, although there was no statistical difference (P = 0.58, HR = 1.82, 95%Cl: 0.22-14.96). Conclusions: The TGP5 in patients with GS 7 had strong association with the risk of BCR and it was an independent predictor for BCR. This result was more obvious in patients with GS 7 (4+3) in our study. Further researches with larger data size were needed to confirm these funding.

The validation of the 2014 International Society of Urological Pathology (ISUP) grading system for patients with high-risk prostate cancer: A single-center retrospective study.

128 Background: Since the new 2014 grading system was recommended by the International Society of Urological Pathology (ISUP), it has been validated in patients with localized prostate cancer (PCa) and has shown excellent prognostic value. However, its predictive power in high-risk PCa remained unclear. Methods: Overall, 420 patients with high-risk PCa who underwent radical prostatectomy (RP) were included. Biochemical recurrence-free survival (BRFS) was set as the endpoint. Results: Biochemical recurrence occurred in 84/420 (20.0%) patients at the end of follow-up. Compared to the three-tier grouping system, the five-tier grouping system could more effectively distinguish the BRFS of patients with higher predictive accuracy (C-index: 0.599 vs 0.646). The BRFS of patients with grade group (GG) 1 and GG 2 was similar (p = 0.593). Also, the prognosis between those in the GG 2 and GG 3 could be clearly distinguished (p = 0.001). Whereas the discrimination capacity between patients with GG 3 and GG 4 was limited (p = 0.681). The high proportion of tertiary Gleason pattern 5 (TGP5) among patients with GG 3 might be an important confounder leading to the overlap of survival between GG 4 and GG 3. Conclusions: This study is the first one to validate the new 2014 ISUP grading system in patients with high-risk PCa who underwent RP. The 2014 system could effectively separate patients into five groups with high predictive accuracy. Notably, the existence of TGP5 needs to be routinely reported in clinical practice, which could help to support the predictive ability of the new grading system.

Integrating tertiary Gleason pattern 5 into the ISUP grading system improves prediction of biochemical recurrence in radical prostatectomy patients

Although the presence of tertiary Gleason pattern 5 is reportedly related to unfavorable prostate cancer characteristics, few data are available regarding the effects of tertiary Gleason pattern 5 on the new ISUP (International Society of Urological Pathology) grading system in radical prostatectomy patients. In this study, we evaluated the effect of tertiary Gleason pattern 5 on biochemical recurrence following radical prostatectomy in patients with prostate cancer. We retrospectively evaluated 1000 patients with prostate cancer who underwent radical prostatectomy. The ISUP Grades were as follows: Grade 1, 16.3%; Grade 2, 48.1% (with tertiary Gleason pattern 5, 8.0% and without tertiary Gleason pattern 5, 40.1%); Grade 3, 21.9% (with tertiary Gleason pattern 5, 9.1% and without tertiary Gleason pattern 5, 12.8%); Grade 4, 3.9%; and Grade 5, 9.8%. Biochemical recurrence-free survival differed significantly among the five groups (Grade 1–5) (P < 0.0001). Grade 2 with tertiary Gleason pattern 5 had a significantly worse prognosis than Grade 2 without tertiary Gleason pattern 5. Similarly, Grade 3 with tertiary Gleason pattern 5 demonstrated a significantly worse prognosis than Grade 3 without tertiary Gleason pattern 5. When Grade 2 and Grade 3 were divided with or without tertiary Gleason pattern 5, the survival curves differed significantly among Grade 1, Grade 2 without tertiary Gleason pattern 5, Grade 2 with tertiary Gleason pattern 5, Grade 3 without tertiary Gleason pattern 5, Grade 3 with tertiary Gleason pattern 5, and Grade 4 (P < 0.0001) (hazard ratios: 1, 1.14, 1.86, 2.23, 3.53, and 6.30). In a multivariate analysis, integrating tertiary Gleason pattern 5 into the ISUP Grade, PSA, and surgical margin status significantly predicted biochemical recurrence (P < 0.0001). Integrating tertiary Gleason pattern 5 into the ISUP grading system will improve the accuracy of patient outcome prediction following radical prostatectomy in patients with prostate cancer.

The impact of tertiary Gleason pattern 5 in the grade group system on recurrence following radical prostatectomy in patients with prostate cancer.

44 Background: The current ISUP/WHO grade group system classified the Gleason grade into five groups. Although presence of tertiary Gleason pattern 5 (tG5) reported to be related with unfavorable tumor characteristic, only a few data is available about influences on the grade group system of tG5 so far. In this study, we evaluated the effect of tG5 on recurrence following radical prostatectomy in patients with prostate cancer. Methods: We retrospectively evaluated 1,020 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. After excluding the patients with missing data or slides, 1000 patients were enrolled in this study. All prostatectomy specimen slides were reviewed by a single genitourinary pathologist according to ISUP 2014. Recurrence following radical prostatectomy was defined according to European Association of Urology guidelines. The endpoint was defined as an increase in PSA level. Results: Patient median age was 67 years (range 49–77 years). The median serum PSA was 6.9 ng/mL (range 0.4–82 ng/mL). The median follow-up period was 69 months (range 0.7–134 months). All the patients showed Group1:163 cases (16.3%), Group2: 436 (43.6%), Group 2 with tG5: 54 (5.4%), Group 3:121 (12.1%), Group 3 with tG5: 89 (8.9%), Group 4: 39 (3.9%), and Group 5: 98 (9.8%). PSA progression-free survival was significantly different among the five groups (Group1-5) (p = 0.0001). As concerning tG5, it showed significant difference between Group 2 and Group 2 with tG5 by using log rank test (p &lt; 0.0001). Similarly, there was significant difference between Group 3 and Group 3 with tG5 (p = 0.001). On the other hand, there was no difference between Group 2 with tG5 and Group 3 (p = 0.916), and in the same way, no difference between Group 3 with tG5 and Group 4 (p = 0.854). Conclusions: The Presence of tG5 on the grade group system increase PSA progression following radical prostatectomy in patients with prostate cancer. Especially, Group 2 and 3 showed upgrade by presence of tG5. Integrating tG5 into the grade group system will improve the accuracy of patient outcome predictions.

Tertiary Gleason pattern in radical prostatectomy specimens is associated with worse outcomes than the next higher Gleason score group in localized prostate cancer

AimTo assess the predictive value of TGP on biochemical recurrence (BCR) and its association with clinicopathological outcomes in a large, multicenter cohort of patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP). Materials and methodsRecords of 6,041 patients who were treated with RP between 2000 and 2011 for clinically nonmetastatic PCa were, retrospectively, analyzed from prospectively collected datasets. BCR-free survival rates were assessed using univariable and multivariable cox-regression analyses. ResultsMedian patient age was 61 years (interquartile range [IQR]: 57–66) with a median preoperative prostrate specific antigen of 6ng/ml (IQR: 4–9). Overall, 28% of patients had Gleason score (GS) 6, 0.3% GS 6 + TGP, 33% GS 7 (3 + 4), 0.2% GS 7 (3 + 4) + TGP, 22% GS 7 (4 + 3), 0.2% GS 7 (4 + 3) + TGP, 0.1% GS 8 and 0.4% GS 9 or 10.Median follow-up was 45 months (IQR: 31–57). Harboring a TGP was associated with higher rates of positive surgical margins, lymphovascular invasion, extraprostatic extension, and seminal vesicle invasion than their counterparts within the same GS group as well as in the next higher GS group (all P ≤ 0.05). At 5 years post-RP, BCR estimates were 5% for patients with GS 6, 13% for patients with GS 6 + TGP, 6% for patients with GS 7 (3 + 4), 22% for patients with GS 7 (3 + 4) + TGP, 16% for patients with GS 7 (4 + 3), 41% for patients with GS 7 (4 + 3) + TGP, 38% for patients with GS 8 (4 + 4) and 46% for patients with GS 9 or 10.Patients harboring a TGP had higher BCR rates than the patients in the next higher GS group: GS 6 + TGP vs. GS 7 (3 + 4), HR = 1.6, P = 0.02 and GS 7 (3 + 4)+TGP vs. GS 7 (4 + 3), HR = 1.4, P = 0.03. Patients with a TGP in the GS 7 (4 + 3) group had comparable BCR rates as patients with GS = 8 (P = 0.4) and GS 9 to 10 (P = 0.2).On multivariable analysis that adjusted for the effects of preoperative prostrate specific antigen, nodal involvement, positive surgical margin, extraprostatic disease (pT3a), seminal vesicle invasion (pT3b) and different institution, harboring a TGP showed higher risk of developing BCR within the same GS group and comparable risk of developing BCR with the next higher GS group. ConclusionPatients with TGP at RP have adverse clinicopathological features when compared to their counterparts in the same and the next higher GS group without TGP. Risk of developing BCR increases with the presence of TGP within the same GS group. This risk seems to be comparable between patients with TGP and their counterparts in the next higher GS group without TGP.Knowledge of TGP in RP specimens is likely to improve risk stratification, patient counseling and follow-up scheduling. Further prospective studies that control significant clinical endpoints such as metastasis and mortality are necessary for more significant predictions.