Pathological Gleason Score Research Articles

The Role of Tumor Oxygenation Tested by Magnetic Resonance Imaging (MRI) in Prostate Cancer Grading.

BackgroundProstate cancer is a common malignant tumor in males. Prostate cancer grading is an important basis for evaluation of invasion. The purpose of this article was to use dynamic enhanced scan magnetic resonance imaging (MRI) to quantitatively investigate the relationship between tumor oxygenation value and prostate cancer pathological Gleason score.Material/MethodsA total of 312 prostate cancer patients diagnosed by needle biopsy who received MRI dynamic enhanced scan were enrolled in this study. Multiparameter oxygen concentration image based on MRI was applied to test pO2 in tumors. Multiple spin resonance image relaxation time edit sequence and weak field diffusion model were used to estimate oxygen saturation level and pO2. hematoxylin and eosin staining and Gleason score were used to determine biological behavior and prognosis.ResultsAccording to the Gleason score system, there were 28 cases with a score of 10, 112 cases with a score of 9, 56 cases with a score of 8, and 116 cases with a score lower than 7. The enrolled patients were divided into groups: 116 cases into the middle-to-well differentiation group (Gleason score ≤7) and 196 cases into the poorly differentiation group (Gleason score at 8 to 10). Prostate cancer tumor oxygenation value was positively correlated with Gleason score (r=0.349, P<0.05) or PSA (r=0.432, P<0.05). Tumor oxygenation value in Gleason ≤7 group was obviously different from that in the group with Gleason score between 9 and 10 (P<0.05).ConclusionsTumor oxygenation value in prostate cancer was positively correlated with Gleason score. Tumor oxygenation value might be useful in clinics to evaluate prostate cancer grading and prognosis.

Predictive Factors and Oncologic Outcome of Downgrade to Pathologic Gleason Score 6⁻7 after Radical Prostatectomy in Patients with Biopsy Gleason Score 8⁻10.

Gleason score (GS) 8–10 is associated with adverse outcomes in prostate cancer (PCa). However, biopsy GS (bGS) may be upgraded or downgraded post-radical prostatectomy (RP). We aimed to investigate predictive factors and oncologic outcomes of downgrade to pathologic GS (pGS) 6–7 after RP in PCa patients with bGSs 8–10. We retrospectively reviewed clinical data of patients with bGS ≥ 8 undergoing RP. pGS downgrade was defined as a pGS ≤ 7 from bGS ≥ 8 post-RP. Univariate and multivariate cox regression analysis, logistic regression analysis, and Kaplan–Meier curves were used to analyze pGS downgrade and biochemical recurrence (BCR). Of 860 patients, 623 and 237 had bGS 8 and bGS ≥ 9, respectively. Post-RP, 332 patients were downgraded to pGS ≤ 7; of these, 284 and 48 had bGS 8 and bGS ≥ 9, respectively. Prostate-specific antigen (PSA) levels; clinical stage; and adverse pathologic features such as extracapsular extension, seminal vesicle invasion and positive surgical margin were significantly different between patients with pGS ≤ 7 and pGS ≥ 8. Furthermore, bGS 8 (odds ratio (OR): 0.349, p < 0.001), PSA level < 10 ng/mL (OR: 0.634, p = 0.004), and ≤cT3a (OR: 0.400, p < 0.001) were identified as significant predictors of pGS downgrade. pGS downgrade was a significant positive predictor of BCR following RP in patients with high bGS (vs. pGS 8, hazard radio (HR): 1.699, p < 0.001; vs. pGS ≥ 9, HR: 1.765, p < 0.001). In addition, the 5-year BCR-free survival rate in patients with pGS downgrade significantly differed from that in patients with bGS 8 and ≥ 9 (52.9% vs. 40.7%, p < 0.001). Among patients with bGS ≥ 8, those with bGS 8, PSA level < 10 ng/mL, and ≤cT3a may achieve pGS downgrade after RP. These patients may have fewer adverse pathologic features and show a favorable prognosis; thus we suggest that active treatment is needed in these patients. In addition, patients with high-grade bGS should be managed aggressively, even if they show pGS downgrade.

A Comprehensive Analysis of the Association Between Gleason Score at a Positive Surgical Margin and the Risk of Biochemical Recurrence After Radical Prostatectomy.

Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.

Outcomes after salvage radical prostatectomy and first-line radiation therapy or HIFU for recurrent localized prostate cancer: results from a multicenter study.

Despite no consensus on the optimal management of recurrent prostate cancer after primary radiation or HIFU therapy, salvage prostatectomy (sRP) is reserved for only 3% of patients because of technical challenges and frequent post-operative complications. We assessed outcomes after sRP in a series of patients with localized PCa and that had received radiation therapy or HIFU as a first-line treatment. Data from nine French referral centers on patients treated with sRP between 2005 and 2017 were collected. Pre- and post-operative data, including oncological and functional outcomes after first treatment and sRP, were analyzed to determine the predictors for biochemical recurrence (BCR) and cancer-specific survival (CSS) after sRP. First-line treatments were external beam-radiation therapy (EBRT) for 30 (55%), brachytherapy (BT) for 10 (18%), and high-intensity focused ultrasound (HIFU) for 15 (27%). Median (IQR) PSA at diagnosis was 6.4 (4.9-9.5)ng/mL, median PSA at nadir was 1.9 (0.7-3.0) ng/mL, and median (IQR) to first BCR was 13 (6-20) months. Of the 55 patients, 44 (80%) received robot-assisted salvage radical prostatectomy and 11 (20%) received salvage retropubic radical prostatectomy. Restoration of continence was achieved in 90% of preoperatively continent patients; 24% that had received nerve-sparing (NS) procedures were potent after surgery. Prolonged catheterization due to anastomotic leakage was the most common complication. Age, preoperative clinical stage, NS procedure, and a pathological Gleason score were predictors for BCR. sRP was safe, feasible, and effective using either an open or robot-assisted approach, in experienced hands. Age, preoperative clinical stage, NS procedure, and pathological GS were linked with BCR after sRP.

Association of macrophage inhibitory factor -173 gene polymorphism with biological behavior of prostate cancer.

Chronic inflammation is an important factor in the etiology of prostate cancer. Macrophage migration inhibitory factor (MIF) plays an important regulatory role in inflammatory responses. The aim of this study was to investigate the potential association between MIF-173 G/C polymorphism, and both biological behavior and incidence of prostate cancer. Analysis of polymorphic variants for MIF was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 128 subjects with prostate cancer and 135 controls. The frequency of MIF-173 *C allele was significantly (OR = 2.18, 95% CI = 1.32-3.61) higher in patients with prostate cancer (19.5%) than in healthy individuals (10%). Prostate cancer patients with Gleason scores ? 7 had higher frequency of MIF-173 *C allele than Gleason scores < 7 (86.1% vs. 27.1%, P = 0.003, OR = 3.18, 95%CI = 1.46-6.95). The frequency of MIF-173 *C allele was significantly different in patients with T1, T2 and ?T3 clinical stages of prostate cancer (15.2% vs. 42.6% and 47.8%, P = 0.003). Our data suggest that MIF-173 polymorphisms may be associated with a higher incidence of prostate cancer compared to controls. We believe that MIF-173 GC+CC genotype can be used as a predictive factor for aggressive behavior of prostate cancer including pathological stage and Gleason scores as well as metastatic potential.

LAPAROSCOPIC RADICAL PROSTATECTOMY OF 926 PATIENTS AT THE HIROSHIMA ENDOUROLOGICAL ASSOCIATION

(Objective) The aim of this study is to investigate the treatment outcome of laparoscopic radical prostatectomy (LRP). (Patients and methods) The study cohort consisted of 926 hormone-naïve patients with localized prostate cancer who underwent LRP at the Hiroshima Endourological Association from January 2007 to December 2016. (Results) The mean age was 69.4 years, the mean initial PSA was 9.1 ng/ml, and the mean follow-up period was 40.3 months. The D'Amico Risk Classification was Low: 232 cases, Intermediate: 344 cases, and High: 350 cases. Nerve preservation was performed bilaterally for 138 patients and unilaterally for 181 patients. The mean operative time was 181.0 minutes and the mean estimated blood loss was 360.7 ml. As the number of experienced cases increased, the operative time was significantly shorter and the estimated blood loss was significantly decreased. According to Clavien-Dindo classification, the ratio of perioperative complication degree IIIa or above was 4.0% (37 cases). The pathological results were Gleason score (GS) ≤6: 174 cases, GS7: 514 cases, GS ≥8: 232 cases, pT2≥: 704 cases, pT3a: 172 cases, pT3b: 47 cases, pT4: 3 cases, pN0: 917 cases, and pN1: 9 cases. Positive surgical margins were found in 278 cases (30.0%). The biochemical recurrence-free survival rate at 5 years was 78.1%. In multivariate analysis, age (≥70 yrs), initial PSA (≥10 ng/ml), biopsy GS (GS ≥8), cancer positive core ratio at biopsy (≥30%), pT (pT≥3), pathological GS (GS≥8), positive surgical margin and total number of patients in the facility were predictive factors of postoperative biochemical PSA recurrence. Younger age and nerve preservation were found to be predictive factors for the early recovery of urinary continence after surgery, with 88% regaining urinary continence at 12 months after surgery. (Conclusion) This study revealed the clinical outcome and appropriate candidates for LRP in Japanese patients.

Unbiased data mining identifies cell cycle transcripts that predict non-indolent Gleason score 7 prostate cancer

BackgroundPatients with newly diagnosed non-metastatic prostate adenocarcinoma are typically classified as at low, intermediate, or high risk of disease progression using blood prostate-specific antigen concentration, tumour T category, and tumour pathological Gleason score. Classification is used to both predict clinical outcome and to inform initial management. However, significant heterogeneity is observed in outcome, particularly within the intermediate risk group, and there is an urgent need for additional markers to more accurately hone risk prediction. Recently developed web-based visualization and analysis tools have facilitated rapid interrogation of large transcriptome datasets, and querying broadly across multiple large datasets should identify predictors that are widely applicable.MethodsWe used camcAPP, cBioPortal, CRN, and NIH NCI GDC Data Portal to data mine publicly available large prostate cancer datasets. A test set of biomarkers was developed by identifying transcripts that had: 1) altered abundance in prostate cancer, 2) altered expression in patients with Gleason score 7 tumours and biochemical recurrence, 3) correlation of expression with time until biochemical recurrence across three datasets (Cambridge, Stockholm, MSKCC). Transcripts that met these criteria were then examined in a validation dataset (TCGA-PRAD) using univariate and multivariable models to predict biochemical recurrence in patients with Gleason score 7 tumours.ResultsTwenty transcripts met the test criteria, and 12 were validated in TCGA-PRAD Gleason score 7 patients. Ten of these transcripts remained prognostic in Gleason score 3 + 4 = 7, a sub-group of Gleason score 7 patients typically considered at a lower risk for poor outcome and often not targeted for aggressive management. All transcripts positively associated with recurrence encode or regulate mitosis and cell cycle-related proteins. The top performer was BUB1, one of four key MIR145-3P microRNA targets upregulated in hormone-sensitive as well as castration-resistant PCa. SRD5A2 converts testosterone to its more active form and was negatively associated with biochemical recurrence.ConclusionsUnbiased mining of large patient datasets identified 12 transcripts that independently predicted disease recurrence risk in Gleason score 7 prostate cancer. The mitosis and cell cycle proteins identified are also implicated in progression to castration-resistant prostate cancer, revealing a pivotal role for loss of cell cycle control in the latter.

Interrelationship Between Health Insurance Status and Prostate Cancer Grade Can Have Critical Impact on Prostate Cancer Disease Control: A Retrospective Cohort Study.

The extent to which prostate cancer (PCa) pathology interacts with health insurance to predict PCa outcomes remains unclear. This study will assess the overall association of health insurance on PCa disease control and analyze its interrelationship PCa pathology. A total of 674 PCa patients, treated with prostatectomy from 1987 to 2015, were included in the study. Freedom from biochemical failure (FFbF) was used as a measure of PCa disease control. Methods of categorical and survival analysis were used to analyze the relationships between health insurance, PCa pathology, and FFbF. A total of 63.3% patients were privately insured, 27.1% were publicly insured, and 9.5% were uninsured. In a multivariable model, privately (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.42-0.97, P = .03) and publicly (HR = 0.65, 95% CI: 0.41-1.04, P = .07) insured patients showed improvement in FFbF compared to uninsured patients. The association of health insurance was significantly stronger for the patients with pathologically low grade PCa (pathologic Gleason Score 3+3 & preoperative prostate-specific antigen ≤10 ng/mL), likelihood ratio P = .009. Privately (HR = 0.22, 95% CI: 0.10-0.46) or publicly (HR = 0.26, 95% CI: 0.11-0.60) insured patients with low grade PCa demonstrated favorable association with FFbF. Patients with private and public insurance were more likely to experience favorable treatment. The association of health insurance on PCa disease control is significantly stronger among patients with pathologically low grade PCa. This study identifies health insurance status as pretreatment surrogate for PCa disease control.

Immunohistochemical expression of ERG and P63 in some prostatic lesions

Background: prostate cancer (PCa) ranks second among the most common types of solid tumors and the sixth among the leading causes of cancer deaths in men worldwide. In Egypt, prostatic cancer formed the majority of male genital cancer (60.7%) at the NCI in the last 10 years. Aim of the work: the present study aimed to detect the immunohistochemical expression of ERG and p63 (as abasal cell marker) in benign prostatic lesions and prostatic carcinoma and to investigate the potential use of ERG and p63 expression levels to discriminate prostatic carcinoma from other lesions and to investigate the association of immunohistochemical expression of ERG with the other prognostic parameters of prostatic carcinoma such as age, plasma PSA level and pathological Gleason score. Methods: fifty prostate lesions, which were collected from the surgical files of the Pathology Department of Al-Azhar University Hospital and from a private lab. Clinicopathological and histological features were taken from patients files and confirmed by H&E examination. Immunohistochemical study was done by using two markers ERG and P63. Results: expression of ERG was restricted to malignant tissue (Prostatic carcinoma) and was negative in BPH and PIN specimens (P. < 0.001) ERG is highly specific but less sensitive marker (40 % of PCa were negative). Expression of ERG revealed inverted significant correlation with Gleason grade and plasma PSA level (P < 0.05). P63 is highly specific and sensitive marker for non-carcinomatous prostatic lesions. Conclusion: ERG showed strong nuclear endothelial expression in all lesions.

The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score is a Novel Significant Prognostic Factor for Patients with Metastatic Prostate Cancer Undergoing Cytoreductive Radical Prostatectomy.

Objective: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been shown to be an important prognostic marker in some tumor types. The aim of this study was to evaluate the prognostic impact of the preoperative HALP score, with the intent to develop a new prognostic index for patients with metastatic prostate cancer (mPCA) after cytoreductive radical prostatectomy (cRP).Methods: We retrospectively analyzed the data from 82 patients with mPCA after cRP in our institution. Of these patients, 70 patients were diagnosed with oligometastatic prostate cancer (oPCA). The main outcome measure was prostate-specific antigen (PSA) progression-free survival (PFS), which was assessed using Kaplan-Meier curves with log-rank statistics. In addition, univariate and multivariate Cox regression analyses were performed to determine the prognostic factors associated with PSA-PFS. The prediction accuracy was evaluated by assessing the area under the receiver operating characteristic (AUC) curve.Results: The median follow-up time for all patients was 17.47 months (range: 11.73-24.38 months). Based on the Kaplan-Meier curve analysis, it was noticed that a low preoperative HALP value (<32.4) was significantly associated with a decreased PSA-PFS in both the mPCA and oPCA subgroups (P < 0.001, P = 0.002, respectively). In addition, multivariate analysis predicted that a low HALP score was a common independent prognostic factor of an overall shorter PSA-PFS (HR: 0.352; range: 0.154-0.804; P = 0.013). However, among the different subgroups, a low HALP score (HR: 0.275; range: 0.116-0.653; P = 0.003) was confirmed to be an independent predictor of a shorter PSA-PFS in patients from the oPCA subgroup. Furthermore, the effective combination of the pathologic Gleason score (PGS) and the HALP score (HALPG) as a new index was found to be an independent risk factor. Also, the AUC of the HALPG score for PSA-PFS was observed to be higher than other conventional clinical indices.Conclusion: Overall, our results confirmed the HALP score as an independent prognostic factor for PSA-PFS in patients with mPCA or oPCA after cRP. Moreover, the new index, HALPG, also appeared to be an independent prognostic factor and was better than the HALP score. Importantly, it is evident that this new prognostic index has the ability to accurately identify patients at low, intermediate, and high risk of recurrence, thus easily allowing informed treatment decisions to be made.

High FOXM1 expression is a prognostic marker for poor clinical outcomes in prostate cancer.

Purpose: We aimed to investigate the expression of FOXM1 and to determine the relationships between FOXM1 expression and clinicopathologic characteristics in patients with PCa. Furthermore, we reconfirmed the prognostic impact of FOXM1 in different cohorts using already published data.Patients and Methods: Formalin-fixed, paraffin-embedded tissues were collected from patients with low- (n=17), intermediate- (n=36), and high-risk (n=29) disease, from patients with CRPC (n=2) and from patients with BPH (n=28). To analyze FOXM1 expression, we performed IHC analyses. Also, we analyzed gene expression data from cBioPortal to evaluate the associations between FOXM1 alteration and prognosis of PCa.Results: FOXM1 expression measured using Allred score differed between patients with BPH, and low-, intermediate-, and high-risk PCa (0.3, 1.5, 4.8, and 6.2, respectively; p<0.001). Patients with high FOXM1 expression had higher preoperative PSA levels (p=0.023), more advanced tumor stages (p=0.047), and higher pathologic Gleason score (p<0.001) than those with low FOXM1 expression. ROC curve analysis indicated that FOXM1 expression was a useful marker for discriminating PCa from BPH (AUC 0.851, 95% CI 0.783-0.920) and for discriminating high-risk PCa from low- and intermediate-risk PCa (AUC 0.807, 95% CI 0.719-0.894). In multivariate analyses, high FOXM1 expression was an independent predictor of BCR. Finally, in the TCGA dataset, FOXM1 alteration was associated with poor overall (p=4.521e-4) and disease-free survival (p=0.0108).Conclusions: In patients with PCa, high FOXM1 expression was associated with advanced tumor stages, high Gleason score, and poor prognosis. These data suggest a role of FOXM1 in biologically and clinically aggressive PCa.

CRTC2 as a novel prognostic biomarker for worse pathologic outcomes and biochemical recurrence after radical prostatectomy in patients with prostate cancer.

PurposeTo identify the association between tumor metabolism and prostate cancer (PCa), we investigated the relationship between expression of metabolism-related genes and clinicopathologic outcomes in patients with localized PCa.Materials and MethodsWe prospectively collected periprostatic adipose tissue from 40 PCa patients and extracted the RNA of each sample. After cDNA was synthesized from the extracted RNA, we analyzed the expression of 18 metabolism-related genes using real-time polymerase chain reaction. We divided the subjects according to the pathologic Gleason score (pGS) and compared the expression of each gene. Subsequently, the clinicopathologic outcomes were also compared according to the expression of each gene.ResultsWhen we compared the expression of 18 metabolism-related genes between the high (≥4+3) and low pGS groups (3+4), there were significant differences in the expression of six genes (SREBP, SCD, FASN, ACLY, ECHS, and CRTC2; p<0.05). Among them, the subjects with low expression for CRTC2 showed significantly worse pathologic outcomes in terms of high pGS (≥4+3) (p=0.020) and higher rates of seminal vesicle invasion (p=0.017). The low CRTC2 group also showed significantly inferior biochemical recurrence-free survival than the high CRTC2 group (p=0.048).ConclusionsWe found that high pGS patients showed significant differences in expression of several metabolism-related genes compared with low pGS patients. Among those genes, CRTC2 showed the strongest association with pathologic outcome, as well as postoperative survival.

Pathological Characteristics of Prostate Cancer in Men Aged < 50 Years Treated with Radical Prostatectomy: a Multi-Centre Study in Korea.

BackgroundRecently, younger prostate cancer (PCa) patients have been reported to harbour more favourable disease characteristics after radical prostatectomy (RP) than older men. We analysed young men (<50 years) with PCa among the Korean population, paying attention to pathological characteristics on RP specimen and biochemical recurrence (BCR).MethodsThe multi-centre, Severance Urological Oncology Group registry was utilized to identify 622 patients with clinically localized or locally advanced PCa, who were treated with RP between 2001 and 2017. Patients were dichotomized into two groups according to age (< 50-year-old [n = 75] and ≥ 50-year-old [n = 547]), and clinicopathological characteristics were analysed. Propensity score matching was used when assessing BCR between the two groups.ResultsAlthough biopsy Gleason score (GS) was lower in younger patients (P = 0.033), distribution of pathologic GS was similar between the two groups (13.3% vs. 13.9% for GS ≥ 8, P = 0.191). There was no significant difference in pathologic T stage between the < 50- and ≥ 50-year-old groups (69.3% vs. 68.0% in T2 and 30.7% vs. 32.0% in ≥ T3, P = 0.203). The positive surgical margin rates were similar between the two groups (20.0% vs. 27.6%, P = 0.178). BCR-free survival rates were also similar (P = 0.644) between the two groups, after propensity matching.ConclusionContrary to prior reports, younger PCa patients did not have more favourable pathologic features on RP specimen and showed similar BCR rates compared to older men. These findings should be considered when making treatment decisions for young Korean patients with PCa.

The correlation analysis of positive surgical margin and biochemical recurrence after robot-assisted laparoscopic radical prostatectomy

Objective To explore the influencing factors and correlation of positive surgical margin (PSM) and biochemical recurrence (BCR) in men after robot-assisted radical prostatectomy (RALP). Methods The clinical data of 190 patients with local or locally advanced prostate cancer who underwent RALP by single surgeon in the Department of Urology of Changhai Hospital from January 2016 to September 2017 were collected. Age was (67.5±6.9) years old; median body mass index (BMI), preoperative PSA, prostate weight were 24.2 kg/m2 (16.6-34.2 kg/m2), 15.0 ng/ml (1.41-393.94 ng/ml) and 36.9 g (8.65-207.58 g) respectively. The group of surgical margin was divided into negative surgical margin, apex-only PSM, base-only PSM as well as apex and base PSM. Characteristics between patients stratified by surgical margin or BCR were compared using χ2 test. The influencing factors of PSM were analyzed by logistic regression. Cox regression was used for the analysis of predictive factors of BCR. Log-rank test and Kaplan-Meier curves were used for comparing the BCR rate between the groups of surgical margin. Results Of all the 190 enrolled patients, total PSM rate was 24.7% (47/190), apex-only PSM rate was 13.2 % (25/190), base-only PSM rate was 5.8% (11/190), apex and base PSM rate was 5.8 % (11/190). Multivariate analysis showed the independent predictive factors influencing PSM were preoperative PSA (P=0.048) and pathological stage (P=0.004 ). The median follow-up period was 7.3 months (0.9-26.6 months) and BCR happened in 19.5% (37/190) patients. The rates of BCR were 15.4% (22/143), 16.0% (4/25), 27.3% (3/11) and 72.7% (8/11) in the patients with negative surgical margin, apex-only PSM, base-only PSM and both apex and base PSM respectively. Log-rank test revealed that the rate of BCR in patients with apex and base PSM was higher than that in patients with negative surgical margin (P<0.001) or patients with apex-only PSM(P=0.002). Cox analysis indicated that higher preoperative PSA (P=0.040), higher pathological stage (P=0.041) and higher pathological Gleason score (P=0.004) were the independent predictors of BCR. PSM was not a predictive factor of BCR (P=0.257). Conclusions Preoperative PSA and pathological stage are the influencing factors of PSM. Higher preoperative PSA, higher pathological stage and higher pathological Gleason Score are the predictive factors of BCR. PSM may not be a predictive factor of BCR. The relationship between PSM and BCR needs further study. Key words: Prostatic neoplasms; Radical prostatectomy; Robot; Positive surgical margin; Biochemical recurrence

Oncologic outcomes in prostate cancer patients treated with robot-assisted radical prostatectomy: results from a single institution series with more than 10 years follow up.

Robot-assisted radical prostatectomy (RARP) has gained increasing diffusion as standard of care in the surgical treatment of prostate cancer (PCa) patients, even in the absence of robust long-term oncologic comparative data. This article is a report of oncologic outcomes of RARP at more than 10 years follow-up. We retrospectively evaluated 173 consecutive PCa patients underwent RARP between 2002 and 2005 at a single European center with complete clinic and pathologic data and potential follow-up of at least 10 years. Kaplan-Meier analyses assessed biochemical recurrence free survival (BCR-FS), clinical recurrence free survival (CR-FS), cancer specific mortality free survival (CSM-FS), other causes mortality free survival (OCM-FS) in the overall population and CR-FS after stratification according to pathologic stage and Gleason score. Multi-variable Cox regression analyses were performed to assess the predictors of BCR and CR. Median follow-up (Interquatile Range [IQR]) was 133 (123-145) months. The BCR-FS, CR-FS, CSM-FS and OCM-FS rates at median follow-up were 73.4%, 81.1%, 95.7%, and 68.6%, respectively. Patients staged as pT3b-T4 and men with Gleason score 8-10 experienced significantly lower CR-FS rates as compared to those with less aggressive pathologic features (all P≤0.001). At multivariable analysis, pathologic Gleason score 8-10 (Hazard Ratio [HR]: 2.85), pathologic stage pT3b-pT4 (HR: 2.76) and adjuvant therapy (HR: 2.09 for radiotherapy [RT] and HR: 13.66 for androgen deprivation therapy [ADT]) were independent predictors of BCR (all p≤0.02). While, pathologic Gleason score 8-10 (HR: 4.05) and pathologic stage pT3b-pT4 (HR: 6.78) were found to be independently related to higher risk of CR (all P≤0.03). Retrospective data and limited number of patients included could have affected our analyses. In experienced centers, RARP allows optimal oncologic outcomes at long term follow-up. Adverse pathologic characteristics are independent predictors of BCR and CR.

Outcomes of men aged ≤50 years treated with radical prostatectomy: a retrospective analysis.

Previous studies investigating prostate cancer (PCa) features in younger men have reported conflicting findings. This study aimed to investigate pathologic outcomes and biochemical recurrence (BCR) status in younger men who underwent radical prostatectomy (RP) for PCa. Records of 2057 patients who underwent RP at Seoul National University Bundang Hospital (Seongnam, Korea) between 2006 and 2015 were reviewed; patients were divided according to age into the younger and older groups (men aged ≤50 and >50 years, respectively). Postoperative BCR status and functional outcomes and clinicopathologic features were compared between both groups. All analyses were repeated after propensity score matching. Younger men were more likely to have low-risk disease (P < 0.001), lower pathologic Gleason score (P < 0.001) and pathologic stages (P < 0.001) than older men. The pathologic Gleason score (P = 0.002) and rates of extracapsular extension (P = 0.004) were lower in younger men after propensity score matching. In multivariate analysis, age at RP was not an independent predictor of BCR-free survival after RP (P = 0.669). Moreover, at 1 year after RP, younger men with preoperative 5-item International Index of Erectile Function score ≥22 (n = 228) showed more favorable results for urinary continence (defined as nonuse of pads daily) (99.4% vs 95%, P = 0.009) and erections sufficient for vaginal intercourse (81.8% vs 55.5%, P = 0.001). Younger men had more favorable clinicopathologic features at RP than their older counterparts. Although age was not an independent predictor of BCR status outcome, younger men had better functional outcomes following RP.

Does race predict the development of metastases in men who receive androgen‐deprivation therapy for a biochemical recurrence after radical prostatectomy?

In this study among men who underwent radical prostatectomy (RP), African American men (AAM) were 28% more likely to develop recurrent disease compared with Caucasian men (CM). However, among those who had nonmetastatic, castration-resistant prostate cancer (CRPC), race did not predict metastases or overall survival. Whether race predicts metastases among men who receive androgen-deprivation therapy (ADT) after a biochemical recurrence (BCR) (ie, before CRPC but after BCR) is untested. The authors identified 595 AAM and CM who received ADT for a BCR that developed after RP between 1988 and 2015 in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database. Univariable and multivariable Cox models were used to test the association between race and the time from ADT to metastases. Secondary outcomes included the time to CRPC, all-cause mortality, and prostate cancer-specific mortality. During a median follow-up of 66 months after ADT, 62 of 354 CM (18%) and 38 of 241 AAM (16%) developed metastases. AAM were younger at the time they received ADT (63 vs 67 years; P < .001), had received ADT in a more recent year (2008 vs 2006; P < .001), had higher prostate-specific antigen levels at RP (11.1 vs 9.2 ng/mL; P < .001), lower pathologic Gleason scores (P = .004), and less extracapsular extension (38% vs 48%; P = .022). On multivariable analysis, there was no association between race and metastases (hazard radio, 1.20; P = .45) or any of the other secondary outcomes (all P > .5). Among veterans who received ADT post-BCR after RP, race was not a predictor of metastases or other adverse outcomes. The current findings suggest that research efforts to understand racial differences in prostate cancer biology should focus on early stages of the disease (ie, closer to the time of diagnosis).

Clinical value of cholinesterase in the prediction of biochemical recurrence after radical prostatectomy

PurposeTo evaluate the predictive and prognostic role as well as the clinical impact on decision-making of serum cholinesterase (ChoE) levels in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer. Materials and methodsWe conducted a retrospective analysis of our multi institutional database. Preoperative ChoE was evaluated as continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with biochemical recurrence (BCR)-free survival. We assessed its association with perioperative clinicopathologic characteristics and outcomes. Multivariable models established its independent prognostic value for BCR. Cox proportional hazard coefficients were used to build nomograms for the prediction of early and late BCR. Decision curve analysis was used to assess the clinical impact on decision making of preoperative ChoE. ResultsIn all, 6,041 patients were available for the analysis. Decreased ChoE was associated with higher biopsy Gleason score, preoperative PSA levels, pathologic Gleason score, pathological stage, lymph node metastasis, positive surgical margin, and lymphovascular invasion at radical prostatectomy (all P < 0.01). Preoperative ChoE ≤ 6.52 U/ml was associated with higher probability of BCR (HR 1.72, 95% CI 1.48–1.99, P < 0.001). Preoperative and postoperative multivariable models that adjusted for the effects of established clinicopathologic features confirmed its independent association with BCR. In decision curve analysis inclusion of preoperative ChoE did not improve the net benefit of preoperative and postoperative models for the prediction of BCR. ConclusionsDespite independent association with clinicopathologic features and BCR, preoperative serum ChoE has no impact on clinical decision making. Future studies should investigate the possible relationship between ChoE activity and neoplastic cell transformation with a rational for targeting.

Impact of metabolic syndrome on oncologic outcomes at radical prostatectomy

PurposeThe associations between metabolic syndrome (MetS) and prostate cancer (CaP) outcomes following radical prostatectomy (RP) are not clear. This study aims to understand the role of MetS in influencing oncological outcomes at RP. Materials and methodsPatients who underwent RP for CaP at our institution from 2000 to 2010 were identified; MetS prior to RP was ascertained with a modified version of the IDF-AHA/NHLBI using ICD-9 codes. Histopathological outcomes included surgical margins, pathological stage, and Gleason score (GS) upgrading. Long-term outcomes included biochemical recurrence (BCR), local recurrence, systemic progression, and CaP-specific mortality. Multivariable adjusted logistic regression and Cox proportional hazards regression assessed the association between MetS status and histopathological and long-term outcomes, respectively. ResultsOf 8,504 RP patients, 1,054 (12.4%) had MetS at the time of RP. MetS patients were older, had higher biopsy GS, but lower pre-op prostatic specific antigen (PSA), higher pathological GS, and larger prostate volume. Adjusted logistic regression suggested an association between MetS and positive margins (odds ratio [OR] = 1.22, P = 0.025) and GS upgrading (OR = 1.28, P = 0.002). There was evidence of an increased risk of local recurrence (hazard ratio [HR] = 1.33, P = 0.037) and CaP-specific mortality (HR = 1.58, P < 0.001) for MetS patients. There was no evidence to suggest an association with BCR or systemic progression. ConclusionMen with MetS are at higher risk of GS upgrade and positive surgical margins at surgery, local recurrence, and CaP-specific mortality. Pathological stage, BCR, and systemic progression were not associated with MetS. Our data may be useful in patients’ counseling, especially when active surveillance is an option.

Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

ABSTRACT Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D’Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D’Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. Abbreviations: PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype.