Final Gleason Score Research Articles

Comparison of Gleason score of Prostate Cancer at Ultrasound/MRI Fusion Target Biopsy vs. Systematic Transrectal Ultrasound Guided Biopsy with Final Gleason score at Radical Prostatectomy

Purpose: To compare accuracy in predicting final Gleason Grade Group (GGG) of Prostate Cancer (PCa) of US/MRI fusion guided target (fBx) vs. systematic Transrectal Ultrasound-Guided (TRUS) biopsy, using histopathologic analysis at prostatectomy as the gold standard. Materials and methods: After obtaining IRB approval, we retrospectively reviewed records of patients who underwent Radical Prostatectomy (RP) from January 2014 through May 2019 with prior US/MRI fusion guided target or TRUS biopsy. The rates of upgrading (RP GGG > BX GGG), downgrading (RP GGG < BX GGG), and concordance (RP GGG = BX GGG) were compared between the fBx and TRUS groups. Age, PSA, PSA density, and prostate volume were also noted for all patients. Statistical analysis was utilized to assess the data. Results: A total of 348 men with complete clinical data were included in this study. The rate of downgrading and upgrading in the fBx group was less than in the TRUS biopsy group (14% vs. 19.6%, and 13.2% vs. 19.6%, respectively). The concordance rate was higher in the US-MR fBx group (72.9% vs. 60.7%, p < 0.05)) across all GGG. Notably, lower rates of concordance were found for GGG 1 (24.1%) and GGG 4 (3.6%) in the TRUS Bx group. Patients who underwent US-MR fBx had higher average PSA (9.4 vs. 6.5 ng/ml), higher PSA density (0.3 vs. 0.2 ng/ml2), and lower prostate volume (31 vs. 42 cc). Additionally, biopsy results showed a lower rate of GGG 1 (3.1% vs. 13.2%) and a higher rate of GGG 5 (14.7% vs. 5.5%) in the US-MR fBx group. Conclusions: Target biopsy has a higher GGG concordance compared to TRUS biopsy (72.9% vs. 60.7%, p < 0.05). In addition, there was less downgrading or upgrading of final PCa GGG in the fBx groups compared to TRUS Bx (14% vs. 19.6%, 13.2% vs. 19.6%, respectively). This finding may have important implications for treatment decisions.

Risk of biochemical recurrence in patients with a positive surgical margin after radical prostatectomy.

Serum prostate specific antigen (PSA) is an irreplaceable marker in the detection and follow-up of patients with prostate cancer. In our analysis we addressed factors that could indicate the likelihood of biochemical recurrence (BCR) early after radical prostatectomy. We mainly focused on the positive surgical margin (R1). Retrospective evaluation and analysis of the database of patients with prostate cancer after radical prostatectomy from 2001 to 2019. In total 1529 patients were enrolled in the study. The median follow-up was 48 months. The age of the patients ranged from 49 to 76 years. We used pre-operative PSA values, and the monitoring of the dynamics of 3rd generation PSA progression (detection limit 0.003 ng/ml) at month 1 and month 3 after surgery and then in 3-month intervals. We monitored the surgical margin positivity (R0 negative, R1 positive) and the Gleason score (GS) based on histological samples and we analysed the relationship to biochemical recurrence of the disease. The pre-operative PSA value did not show a direct relationship to the R1 risk. Patient values in the groups R1 and R0 differed only by 1.159 ng/ml (p=NS). The 3rd generation PSA value at month 1 after surgery was 50.82% higher in R1 patients (p>0.001). 50% of patients with R1 (29.5% patients of the total) did develop BCR during the follow-up period, while in patients with R0 (70.5% patients of the total) this proportion was 30% (p>0.001). Among those with GS 67, 47% developed BCR. The GS 810 group relapsed in 75% of the cases (p>0.001). According to our analysis 33% of the patients reached the stage of biochemical recurrence. We demonstrated a direct dependency between the risk of recurrence and the final Gleason score. The presence of R1 should not be viewed as a direct indication for adjuvant radiotherapy.

Consistencies and inconsistencies of Gleason score and grade group system in prostate biopsy and radical prostatectomy

The diagnostic of prostatic adenocarcinoma (PADK) is based on two scoring systems, namely the Gleason grading system and the grade group system - both of them being included in the pathology report. There is a discrepancy in the Gleason score given on the initial biopsy and prostatectomy specimen, respectively, that affects both patients who can benefit from active surveillance and those who cannot benefit from curative surgical treatment, and for whom therapeutic alternatives must be established. In this context, our study aimed at analyzing the diagnostic concordance between biopsies and subsequent prostatectomies, in order to establish the accuracy of prostate biopsy in predicting final Gleason score of the prostatectomy specimens. Material and methods: We analyzed 79 cases of PADK, initially diagnosed by prostate biopsy and subsequently treated by radical prostatectomy. The accuracy degree of the tumoral grading system assigned to the prostate biopsy, compared with the radical prostatectomy, was assessed by calculation of the Cohen's kappa concordance coefficient and calculation of sensitivity, specificity, positive prognostic value and negative prognostic value. Results: 37 cases (46.83%) presented the same Gleason score given for prostate biopsies and radical prostatectomies. In prostate biopsies, 32 cases (40.50%) were underestimated, compared to the Gleason score established by evaluating radical prostatectomy specimens, and 10 cases (12.65%) were overestimated. The highest agreement rate between the Gleason score in prostate biopsy and radical prostatectomy was found for Gleason score 6 (3+3) and 7 (3+4)-17 cases (21.51%) for each score category. The lowest agreement rate was observed for Gleason score 5, where no case showed a similar score for biopsy and prostatectomy. Statistical analysis indicated a kappa coefficient of 0.23, corresponding to a statistically significant satisfactory agreement (p = 0.01). The agreement on ISUP prognostic grade groups between prostate biopsy and radical prostatectomy indicated a slight increase in kappa coefficient -0.41, while maintaining a statistically significant moderate agreement (p = 0.0001). Conclusions: Our results demonstrate an increase in the predictive accuracy of prostate biopsy, as a result of the application of prognostic grade group system, which ensure the decrease of overestimating tendency of the old scoring system, ultimately leading to a preliminary characterization of potential lesions in prostatectomy specimens and a more effective treatment stratification of patients.

Correlation of MRI-Lesion Targeted Biopsy vs. Systematic Biopsy Gleason Score with Final Pathological Gleason Score after Radical Prostatectomy.

Background: The impact of MRI-lesion targeted (TB) and systematic biopsy (SB) Gleason score (GS) as a predictor for final pathological GS still remains unclear. Methods: All patients with TB + SB, and subsequent radical prostatectomy (RP) between 01/2014-12/2020 were analyzed. Rank correlation coefficient predicted concordance with pathological GS for patients’ TB and SB GS, as well as for the combined effect of SB + TB. Results: Of 159 eligible patients, 77% were biopsy naïve. For SB taken in addition to TB, a Spearman’s correlation of +0.33 was observed regarding final GS. Rates of concordance, upgrading, and downgrading were 37.1, 37.1 and 25.8%, respectively. For TB, a +0.52 correlation was computed regarding final GS. Rates of concordance, upgrading and downgrading for TB biopsy GS were 45.9, 33.3, and 20.8%, respectively. For the combination of SB + TB, a correlation of +0.59 was observed. Rates of concordance, upgrading and downgrading were 49.7, 15.1 and 35.2%, respectively. The combined effect of SB + TB resulted in a lower upgrading rate, relative to TB and SB (both p < 0.001), but a higher downgrading rate, relative to TB (p < 0.01). Conclusions: GS obtained from TB provided higher concordance and lower upgrading and downgrading rates, relative to SB GS with regard to final pathology. The combined effect of SB + TB led to the highest concordance rate and the lowest upgrading rate.

Prognostic value of FUS immunoexpression for Gleason patterns and prostatic adenocarcinoma progression

BackgroundRisk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. Patients and methodsNon-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. ResultsOur cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203–2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878–1.499]; p = 0.313). ConclusionNon-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.

Evaluation of multiparametric prostate magnetic resonance imaging findings in patients with a Gleason score of 6 in transrectal ultrasonography-guided biopsy.

PurposeWe aimed to evaluate prostate multiparametric magnetic resonance imaging (mpMRI) findings of patients with a Gleason score (GS) of 6 and effectiveness of MRI based on the final pathology result in patients undergoing radical prostatectomy (RP).Material and methodsmpMRI findings of 80 patients who had a GS of 3 + 3 and who underwent mpMRI were evaluated retrospectively. The mpMRI were scored according to the PIRADS v2.1 guidelines. The patients were divided into those with a high probability of clinically significant cancer (CSC) (PI-RADS 4-5) and those with a low probability of CSC (PI-RADS 2-3).ResultsOf the 80 patients, 33.8% had PI-RADS 2-3, and 66.2% had PI-RADS 4-5 lesions. There was a significant difference between the groups in prostate specific antigen (PSA) value, PSA density, patient age, and tumour percentage on biopsy. When the pathology results were taken as the gold standard in the group that underwent RP, sensitivity, specificity, and accuracy of mpMRI were calculated as 94.74%, 100%, and 96.3%, respectively, an increase in the final GS was found in 9 (33.3%) of the 27 patients, and 70.35% of patients were identified as having CSC.ConclusionsPI-RADS 4-5 scores have high sensitivity and negative predictive value in the diagnosis of CSC. mpMRI is a reliable and non-invasive diagnostic method that can complement biopsy results in decision-making in patients who are initially evaluated as low risk.

Is a sampling transition zone important to increase the detection of prostate cancer in systematic prostatic biopsies?

Use of transrectal ultrasound (US)-guided biopsies improved diagnosis and treatment for patients with high prostate-specific antigen (PSA) or abnormal digital rectal exam (DRE). To investigate whether taking two transition zone (TZ) biopsies in addition to routine prostate double-sextant biopsies (12-cores) would improve detection rates of prostate cancer (PCa). A retrospective analysis of 1107 in a single institution database after Institutional Review Board approval, which underwent US-guided prostate biopsies from January 2014 to June 2016. All patients with suspected PCa based on positive DRE or high PSA submitted to US-guided prostate biopsy (double-sextant 12-cores alone and 12-cores with two TZ extra cores) were included. A total of 1107 patients were included; 120 patients underwent double-sextant 12-cores alone and 987 underwent 12-cores with two TZ extra cores. Among patients submitted to two TZ extra cores, TZs of 755 (76.5%) patients were negative to neoplasia and 232 (23.5%) were positive to neoplasia. Among these patients, 26 (2.6%) had their final Gleason score increased with TZ core; TZ fragments of 20 (2.0%) patients led to a treatment change (re biopsy, active surveillance or from active surveillance to radiation therapy or radical prostatectomy). When the complication rate is analyzed (with or without hospital admission), among the patients submitted to TZ cores, 259 (26.2%) complications were observed; between those submitted to double-sextant 12-cores, 26 (21.7%) complications were observed (P=0.279). Extended core biopsy protocol with two TZ extra fragments improves detection rates of cancer when compared to double-sextant biopsy protocol without increasing complication rates. TZ routine cores should be considered.

Evaluation of relationships between the final Gleason score, PI-RADS v2 score, ADC value, PSA level, and tumor diameter in patients that underwent radical prostatectomy due to prostate cancer.

This study aimed to investigate the relationship between the serum PSA level, Gleason score (GS), PI-RADS v2 score, tumor ADCmin value, and the largest tumor diameter in patients that underwent radical prostatectomy (RP) due to prostate cancer (PCa) and to comparatively evaluate the variables of these parameters in clinically significant and insignificant PCa groups. The mpMRI examinations of the patients who underwent RP due to PCa were retrospectively evaluated. According to the final GS, the lesions were divided into two groups as clinically significant (GS ≥ 7) and insignificant (GS ≤ 6). The PSA value, tumor ADCmin value, tumor diameter, and PI-RADS score were compared between the clinically significant and nonsignificant PCa groups using Student's t-test. The correlations between the serum PSA level, GS, PI-RADS v2 score, tumor ADCmin value, and tumor diameter were evaluated separately (Pearson's correlation analysis was used for peripheral gland tumors, and Spearman's correlation analysis for central gland tumors). A ROC analysis was undertaken to evaluate the efficacy of the tumor ADCmin, diameter and PSA values in differentiating clinically significant and nonsignificant tumors. In both central and peripheral gland tumors, there was a correlation between the PSA level, tumor diameter, PI-RADS score, ADCmin value, and GS at various levels (poor, moderate, and high). In central gland tumors, there was no significant difference between the two groups in terms of the PSA value and PI-RADS scores (p > 0.05), but the ADCmin value and diameter of the tumor significantly differed (p < 0.05). For peripheral gland tumors, significant differences were observed in all parameters (p < 0.05). The cut-off values for the peripheral and central gland tumors are as follows: lesion diameter, 13.5mm and 19mm; tumor ADCmin, 0.709 × 10-3mm2/s and 0.874 × 10-3mm2/s; and PSA level, 8.47ng/ml and 11.10ng/ml, respectively. The current PI-RADS v2 scoring system can be inadequate in distinguishing clinically significant and insignificant groups in central gland tumors. A separate cut-off value of the tumor diameter should be determined for central and peripheral gland tumors. Tumor ADCmin values can be used as a predictive parameter. The PSA cut-off value should be kept lower in peripheral gland tumors.

Prospective comparison of 68Ga-RM2 PET/CT and 68Ga-PSMA-617 PET/CT for initial staging of prostate cancer.

21 Background: PSMA ( Prostate Specific Membrane Antigen) and GRP-R ( Gastrin Releasing Peptide Receptor) are overexpressed on prostatic cancer cells and can be targeted with a PSMA inhibitor such as 68Ga-PSMA-617 (Liu 2018) or a GRP-R antagonist such as 68Ga-RM2 (Touijer 2019). We aimed to compare 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT at initial staging of prostate cancer. Methods: We prospectively enrolled 10 treatment-naïve patients with biopsy-confirmed prostate cancer. Fifteen lesions were found (two with Gleason score (GS) 6; seven GS 7(3+4), two GS 7(4+3) and four GS ≥ 8). 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT were randomly performed before prostatectomy with imaging at 1 and 2 hours after injection (2MBq/kg). Manual (MS) and automatic (AS) segmentation were performed on each PET imaging and then compared to histology (standard-of- truth). Prostatectomy samples were analyzed by an experimented pathologist who identified and staged each lesion according to GS. Each prostatectomy slice available was scanned for comparison between PET and histologic segmentation. Uptake intensity (SUVmax) and signal-to-noise ratio (SNR) relative to non-lesional prostate gland parenchyma were analyzed. Per-lesion analysis was performed on final GS (prostatectomy). Results: Using AS, 68Ga-RM2 PET/CT showed better sensitivity (Se) than 68Ga-PSMA-617 PET/CT: (0.85 vs 0.75) and better specificity (Sp) (0.89 vs 0.60). MS found similar Se (0.94 vs 0.93) but better Sp (0.89 vs 0.80) with 68Ga-RM2 PET/CT. SNR of 68Ga-RM2 PET/CT was high whatever the GS was; while 68Ga-PSMA-617 PET/CT exhibited higher SNR in high GS (p = 0.044). Finally, in low GS, SNR of 68Ga-RM2 PET/CT was significantly higher than 68Ga-PSMA-617 PET/CT (p = 0.004). Conclusions: GRP-R-targeting and PSMA-targeting have been previously compared in patients with biochemically recurrence (Minamimoto 2016) but not at primary staging. Our initial results, in this indication, showed great diagnostic performance of 68Ga-RM2 PET/CT compared to 68Ga-PSMA-617 PET/CT to characterize low Gleason score tumors. 68Ga-PSMA-617 PET/CT is promising for initial staging of high Gleason score tumors. These results need to be confirmed in a larger study.

Curative effects of anatomic reconstruction of periurethral structure in robotic assisted laparoscopic radical prostatectomy

Objective To investigate the outcome of patients underwent anatomic periurethral reconstruction during robotic assisted laparoscopic radical prostatectomy (RARP). Methods During August 2016 to May 2018, anatomic periurethral reconstruction was performed during RARP in 58 consecutive patients. The control group consists of another 50 patients had no anatomic periurethral reconstruction procedure during RARP.Perioperative data of these patients were collected retrospectively, including operation time, anastomosis timeintraoperative blood loss, duration of indwelling catheter, length of hospital stay, complications, postoperative pathology, and continence outcome at 1, 3, 6, 12 months after surgery. Results All cases were successfully performed without conversion to open or laparoscopic surgery. There were no major intraoperative or postoperative complications. Operative time and anastomosis time was (145.3±12.3)mins and (31.6±8.2)mins in reconstruction group comparing to (122.4±11.4)mins and (21.2±4.4) in control group (both P 0.05). Postoperative pathology confirmed 53 T2a-T2b diseases and 5 pT2c diseases in reconstruction group, in comparison with 46 T2a-T2b and 4 pT2c diseases in non-reconstruction group (P>0.05). There were 19 and 15 cases with a final Gleason score of 6, 30 and 27 cases with Gleason 7, 9 and 10 cases with Gleason 8, in reconstruction group and non-reconstruction group respectively(all P>0.05). There was no significant difference between the two groups regarding incidence of positive surgical margins (3 in reconstruction group and 2 in control group, P>0.05). The percentage of patients maintain continence in reconstruction group and non-reconstruction group: at 1 month [84.5%(49/58)and 70.0%(35/50)], at 3 months [89.7%(52/58)and 78.0%(39/50)], at 6 months [91.3%(53/58)and 86.0%(43/50)] and 1 year after surgery [100.0%(58/58)and 96.0%(48/50)]. Reconstruction group showed better continence outcome at 1 and 3 month (P 0.05). Conclusion Anatomic reconstruction of periurethral structure during RARP is safe and feasible with reduced duration of indwelling catheter and better continence outcome. Key words: Robotic assisted laparoscopic surgery; Radical prostatectomy; Incontinence; Enhanced recovery after surgery

MRI-TRUS fusion-guided biopsy in obese patients: Does it reduce risk of prostate cancer upgrade on final pathology compared to systematic 12-core biopsy?

110 Background: Epidemiologic data suggests a link between obesity and increased risk of aggressive prostate cancer (PCa). Therefore, the accurate detection of prostate cancer is paramount in obese men. We sought to characterize the PCa lesions seen on multiparametric magnetic resonance imaging (mpMRI) in both obese (OB) and non-obese (nOB) patients. In addition, we examined whether obesity affects the accuracy of fusion biopsy (FBx) versus systematic biopsy (SBx). Methods: Data from patients who underwent FBx, SBx, or both, and subsequent prostatectomy at a single institution between 2007-2017 were reviewed. Men were stratified into three groups based on body mass index (BMI): normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). mpMRIs were analyzed to determine prostate size, lesion size, lesion location, and evidence of ≥T3 disease. FBx and SBx were compared to prostatectomy specimens. These variables were then analyzed between the OB and nOB groups. Results: 487 patients were included: 109 (19%) normal weight, 266 (48%) overweight, and 185 (33%) obese. No statistical differences were noted in age, PSA, or clinical stage. mpMRI showed similar prostate size, index and total lesion diameter, lesion location, and Prostate Imaging Reporting and Data System (PIRADS) score between BMI categories. In OB patients, FBx was better able to predict final Gleason score (GS) than SBx, 60% vs 47%, p = 0.0474, OR 1.67 (1.00-2.80). The rate of upgrading after SBx was higher for OB men versus nOB men, 44% vs 34%, p = 0.034, OR 1.52 (1.01-2.29). However, risk of upgrading returned to that of nOB men with FBx, 20% vs 17%, p = 0.538, OR 1.21 (0.658-2.23). Conclusions: FBx is a more accurate measure of the true GS in OB patients than SBx, and there is a significantly greater risk of underrepresenting PCa on SBx in OB patients. These findings were not associated with differences in prostate sizes and lesion characteristics on mpMRI. This suggests that obesity may cause technical challenges with prostate biopsies that may be overcome by improved visualization and targeting of FBx.

Oncological Outcomes of Open Radical Retropubic Prostatectomy in Ireland: A Single Surgeon's 5-Year Experience.

Objectives There is a little published data on the outcomes of radical prostatectomy in the Irish context. We aimed to determine the 5-year oncological results of open radical retropubic prostatectomy (RRP) performed by a single surgeon following appointment. Methods A retrospective review of RRPs performed between 2011 and 2016 was conducted. Patient demographics, preoperative parameters (clinical stage on digital rectal exam, prostate-specific antigen (PSA) levels, biopsy Gleason's score and MRI [magnetic resonance imaging] findings), pathological variables (T-stage, Gleason's score, nodal status, and surgical margin status), and treatment decisions (lymphadenectomy or adjuvant radiotherapy) were recorded. Oncological outcome at last follow-up was ascertained. Results 265 patients underwent RRP between 2011 and 2016. Median age was 62 years (range: 41–74). Mean follow-up was 32.24 months (range: 8–72) months. Pathological disease stage was T2 in 170/265 (64.15%), T3a in 65/265 (24.53%), and T3b in 30/265 (11.32%). Final Gleason's score was upgraded from diagnostic biopsy in 16.35% (43/263) and downgraded in 27% (71/263). Pelvic lymph node dissection was performed in 44.25% (118/265) patients. A positive surgical margin (PSM) was seen in 26/170 (15.2%) patients with T2 disease and in 45/95 (47.37%) patients with T3 disease. Of the 265 patients, 238 (89.81%) were disease-free at last follow-up, of whom 24/238 (10.08%) had received adjuvant and 17/238 (7.14%) received salvage radiotherapy. Adjuvant/salvage treatment was ongoing in 19/265 (7.17%) of patients. Conclusion Good oncological outcomes of RRP in the Irish context are seen in this 5-year review, with the vast majority of patients experiencing biochemical-free survival at most recent follow-up.

Localized prostate cancer and robot-assisted laparoscopic radical prostatectomy: a retrospective, comparative study between pre- and post-operative Gleason scores

Introduction: To compare the pre- and post-operative Gleason scores (GS) in patients with localized prostate cancer treated with robot-assisted laparoscopic radical prostatectomy.Materials and methods: A single center, retrospective comparison between pre- and post-operative GS. Age, prostate volume, PSA, number of biopsies, number of positive cores, biopsy GS, cTNM, final pathology GS and pTNM of 286 patients were retrieved. They were divided into risk groups.Results: A total of 286 patients with a mean age at surgery of 64.64 ± 7.81 y and mean PSA-value of 9.35 ± 8.38 ng/mL. Mean prostate volume was 55.09 ± 24.93 mL, mean number of biopsies was 11.90 ± 4.63. Mean percentage of positive cores was 36.90 ± 22.42%. A GS of <7 was seen in 23.4%, 66.8% had a GS of 7 and 9.7% of >7 in final pathology. Of the total, 38.1% were pre-operative low risk, 58.7% of them had an upgrade in GS on final pathology, 45.1% were in the intermediate risk group, 5.4% showed a downgrade, 64.3% remained stable and 30.2% had an upgrade in GS. Also, 16.8% were high risk patients of which 35.4% had a downgrade, 39.6% remained stable and 25% showed an upgrade of the GS.Conclusions: We found a substantial underestimation of the GS in the pre-operative setting when compared to the GS in final pathology.

The significance of De Ritis (aspartate transaminase/alanine transaminase) ratio in predicting pathological outcomes and prognosis in localized prostate cancer patients.

To illustrate whether De Ritis (aspartate transaminase-AST/alanine transaminase-ALT) ratio is useful in risk stratification of localized prostate cancer and propose an easy predictive model for biochemical recurrence-free survival (BCRFS). In total, 438 patients who underwent radical prostatectomy were included in this study. Blood samples including AST and ALT were collected 1-7days before surgery. An elevated AST and ALT value was defined as over 40 or 56IU/L. The median AST and ALT value was 18.5 (16-22) and 14 (11-18) IU/L. In total, 15 patients (3.4%) and 9 patients (2.1%) exhibited elevated AST value and ALT value. The median De Ritis ratio was 1.33 (1.11-1.60), and ROC curve indicated the best cutoff of 1.325 in predicting the occurrence of biochemical recurrence. Higher De Ritis ratio was found to be related to older age (p<0.001), higher tumor stages (p<0.001) and Gleason Score (p<0.001), presence of seminal invasion (p<0.001), positive surgical margin (p<0.001) and lymph node metastasis (p=0.003). Multivariate logistic regression confirmed that De Ritis ratio was an independent predictor for final Gleason Score (p<0.001), and multivariate Cox regression demonstrated De Ritis ratio as an independent risk factor for BCRFS. A simple predictive model which incorporated De Ritis ratio, pathological tumor stage and final Gleason Score could help risk stratification for BCRFS. Higher De Ritis ratio could be predictive for worse pathological outcomes and higher BCR in localized prostate cancer patients. A predictive model which incorporates De Ritis ratio, Gleason Score and pathological tumor stage could help risk stratification for BCRFS.

Pathologic correlation of transperineal in-bore 3-Tesla magnetic resonance imaging-guided prostate biopsy samples with radical prostatectomy specimen.

To determine the accuracy of in-bore transperineal 3-Tesla (T) magnetic resonance (MR) imaging-guided prostate biopsies for predicting final Gleason grades in patients who subsequently underwent radical prostatectomy (RP). A retrospective review of men who underwent transperineal MR imaging-guided prostate biopsy (tpMRGB) with subsequent radical prostatectomy within 1 year was conducted from 2010 to 2015. All patients underwent a baseline 3-T multiparametric MRI (mpMRI) with endorectal coil and were selected for biopsy based on MR findings of a suspicious prostate lesion and high degree of clinical suspicion for cancer. Spearman correlation was performed to assess concordance between tpMRGB and final RP pathology among patients with and without previous transrectal ultrasound (TRUS)-guided biopsies. A total of 24 men met all eligibility requirements, with a median age of 65 years (interquartile range [IQR] 11.7). The median time from biopsy to RP was 85 days (IQR 50.5). Final pathology revealed Gleason 3+4=7 in 12 patients, 4+3=7 in 10 patients, and 4+4=8 in 2 patients. A strong correlation (ρ: +0.75, p<0.001) between tpMRGB and RP results was observed, with Gleason scores concordant in 17 cases (71%). 16 of the 24 patients underwent prior TRUS biopsies. Subsequent tpMRGB revealed Gleason upgrading in 88% of cases, which was concordant with RP Gleason scores in 69% of cases (ρ: +0.75, p<0.001). Final Gleason scores diagnosed by tpMRGB at 3-T correlate strongly with final RP surgical pathology. This may facilitate prostate cancer diagnosis, particularly in patients with negative or low-grade TRUS biopsy results in whom clinically significant cancer is suspected or detected on mpMRI.

Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection.

To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2-6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8-10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

Improved decision making in intermediate-risk prostate cancer: a multicenter study on pathologic and oncologic outcomes after radical prostatectomy.

Prognoses for intermediate-risk prostate cancer (PCa) remain heterogeneous. Improved substratification could optimize treatment and monitoring strategies. The objective was to validate this subclassification in a radical prostatectomy (RP) series. Between 2000 and 2011, 4038 patients who underwent RP for intermediate-risk PCa in seven French academic centers were included. Unfavorable intermediate-risk (UIR) PCa was defined as having a primary Gleason score of 4, ≥50% positive biopsy cores (PPBC), or more than one D'Amico intermediate-risk factor (i.e., cT2b, PSA 10-20, or Gleason score 7). Remaining PCa cases were classified as favorable. Main endpoints were pathologic results (pT stage, final Gleason score, surgical margin status), and oncologic outcomes were assessed according to PSA recurrence-free survival (PSA-RFS). Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. Median follow-up was 48months (95% CI=[45-49]). Patients with UIR had worse PSA-RFS (68.17 vs. 81.98% at 4years, HR=1.97, 95% CI=[1.71; 2.27], p<0.0001) compared to those with a favorable disease. The need for adjuvant therapy was significantly greater for UIR patients (43.5 vs. 29.2%, p<0.0001). In multivariate analysis, primary Gleason score of 4 (HR=1.81, 95% CI=[1.55; 2.12], p<0.0001) and PPBC≥50% (HR=1.26, 95% CI=[1.02; 1.56], p=0.0286) were significant preoperative predictors for worse PSA-RFS. This study highlights the heterogeneity of NCCN intermediate-risk patients and validates (in a large RP cohort) the previously proposed subclassification for this group. This classification can significantly predict both pathologic and oncologic outcomes. This easy-to-use stratification could help physicians' decision making. Prospective study and new tools as genomic tests and novel molecular-based approaches can improve this stratification in the future for patient counseling.

Nomograms for predicting Gleason upgrading in a contemporary Chinese cohort receiving radical prostatectomy after extended prostate biopsy: development and internal validation

The current strategy for the histological assessment of prostate cancer (PCa) is mainly based on the Gleason score (GS). However, 30-40% of patients who undergo radical prostatectomy (RP) are misclassified at biopsy pathologically. Thus, we developed and validated nomograms for the prediction of Gleason score upgrading (GSU) in patients who underwent radical prostatectomy after extended prostate biopsy in a Chinese population. This retrospective study included a total of 411 patients who underwent radical prostatectomy at our institute after having prostate biopsies between 2011 and 2015. The final pathologic GS was upgraded in 151 (36.74%) of the cases in all patients and 92 (60.13%) cases in men with GS=6. In multivariate analyses, the primary biopsy GS, secondary biopsy GS and obesity were predictive of GSU in the patient cohort assessed. In patients with GS=6, the significant predictors of GSU included the body mass index (BMI), prostate-specific antigen density(PSAD) and percentage of positive cores. The area under the curve (AUC) of the prediction models was 0.753 for the entire patient population and 0.727 for the patients with GS=6. Both nomograms were well calibrated, and decision curve analysis demonstrated a high net benefit across a wide range of threshold probabilities. This study may be relevant for improved risk assessment and clinical decision-making in PCa patients.

Comparison of Perioperative and Early Oncologic Outcomes between Open and Robotic Assisted Laparoscopic Prostatectomy in a Contemporary Population Based Cohort

We compared rates of positive surgical margins, use of postoperative radiation therapy, and perioperative outcomes between robotic assisted laparoscopic and open radical prostatectomy in a contemporary population based cohort. In the National Cancer Data Base from 2010 through 2011 patients who underwent robotic assisted laparoscopic prostatectomy (73,131) and open radical prostatectomy (23,804) for nonmetastatic prostate adenocarcinoma were identified. Covariates included age, race, Charlson comorbidity index, prostate specific antigen, biopsy Gleason score, clinical stage, final Gleason score, pathological T stage, lymph node dissection, nodal status, facility type, hospital volume and year of surgery. Multivariable logistic regression was used to identify factors associated with positive surgical margins, use of adjuvant/salvage radiation therapy, prolonged length of stay, readmission and 30-day mortality. Outcomes were also compared in 1:1 propensity matched cohorts. Analysis of propensity matched cohorts showed robotic assisted laparoscopic prostatectomy reduced the risk of positive surgical margins (OR 0.88, 95% CI 0.83-0.93, p <0.01), the use of radiation therapy (OR 0.71, 95% CI0.63-0.80, p <0.01) and 30-day mortality (OR 0.28, 95% CI 0.13-0.60, p<0.01). The protective effect of robotic assisted laparoscopic prostatectomy for positive surgical margins was found in patients with pT2 disease only (pT2-OR 0.85, 95% CI 0.79-0.91, p <0.01; pT3-OR 0.94, 95% CI 0.86-1.04, p=0.2). Similar results were obtained using multivariable regression. In a contemporary large national cohort, robotic assisted laparoscopic prostatectomy was independently associated with clinically meaningful reductions in positive surgical margins, postoperative radiation therapy and 30-day mortality compared to open radical prostatectomy. The oncologic benefit was primarily in patients with organ confined disease. Limitations were those associated with any observational study, namely the potential for bias due to unmeasured confounders.

Gleason grading challenges in the diagnosis of prostate adenocarcinoma: experience of a single institution.

Gleason score (GS) is an important factor in determining management and outcome of prostate adenocarcinoma. A standard GS scheme was introduced by ISUP 2005 consensus conference, but there is still significant discordance in grading prostate adenocarcinomas among pathologists, especially between genitourinary-trained (GU) and non-GU pathologists. All biopsies from outside institutions referred for definitive treatment in our hospital are reviewed by a GU pathologist for confirmation and quality assurance. From 2011 to 2013, 117 consecutive prostate consults were retrieved and compared with the initial outside reports as well as final radical prostatectomy (RP) results. Follow-up prostate specific antigen (PSA) was assessed pre- and post-RP, and the results were analyzed. The overall initial GS was higher for all specimens (p = 0.007) especially for the RP cases (p = 0.002). Overall, the modal GS on initial diagnosis was GS7(4 + 3) that was downgraded to the modal GS6(3 + 3) upon review. Despite an overall substantial agreement between the non-GU and GU pathologists [ICC = 0.66], GS by GU pathologist had higher correlation with the final GS in the RP specimen [ICC = 0.62] than non-GU pathologist [ICC = 0.48]. GS on all reviewed cases were found to correlate significantly with the pre-operative PSA (p = 0.002) but the same was not true for the initial report. A non-GU pathologist is more likely to assign a higher GS than a GU pathologist, with a trend to overcall Gleason pattern 4. Considering the implications on treatment, close attention must be paid to the ISUP 2005 consensus conference recommendations.