Prognostic Factor For Biochemical Recurrence Research Articles

Current Imaging Techniques for Lymph Node Staging in Prostate Cancer: A Review.

Introduction: Lymph node metastases (LNM) represent a proven prognostic factor for biochemical recurrence (BCR)-free survival, metastatic free survival and overall survival in prostate cancer (PCa). Although pelvic node dissection remains the gold standard for the detection of LNM, novel imaging techniques are entering clinical practice, in the effort to improve LNM detection and spare unnecessary surgeries. Aim of the current review is to describe such imaging techniques and explore their advantages and limitations.Evidence Acquisition: The National Library of Medicine Database was searched for relevant articles published between January 2013 and August 2018. A wide search was performed including the combination of following words: “Prostate” and “Cancer” and “staging” and “Lymph Node” and “imaging” and (“MRI” or “PET”). The initial list of selected papers was enriched by individual suggestions of the authors of the present review.Evidence Synthesis: DWI-MRI in detection of lymph node invasion has a sensitivity and specificity of 41 and 94%, respectively. For SPIO MRI using ferumoxtran-10, the sensitivity for detection of LNM with short axis diameter of 5–10 mm is reported at 96.4%, compared to 28.5% with MRI alone. PSMA PET/CT is growing exponentially, both in the initial detection of LNM and for BCR evaluation. Fluciclovine PET could improve detection of subcentimetric pathologic lymph nodes. Sentinel lymph node techniques remain experimental and not validated in the field of PCa.Conclusions: Molecular imaging, particularly PSMA ligand PET imaging, present interesting diagnostic accuracy in LN diagnosis even in subcentimetric LN. DWI-MRI yields good results in LN involvement evaluation and the use of contrast agent such SPIO may improve the detection rate. The SLN technique is limited to experimental protocols and for intermediate or high-risk PCa. Prospective trials are awaited to evaluate the true clinical impact of these imaging techniques on PCa oncologic outcomes.

Pre-treatment 18F-choline PET/CT is prognostic for biochemical recurrence, development of bone metastasis, and cancer specific mortality following radical local therapy of high-risk prostate cancer

BackgroundThe aim of this study was to determine whether lymph node metastasis on pre-treatment 18F-choline PET/CT is an independent prognostic factor for biochemical recurrence (BCR), skeletal metastasis, and cancer specific mortality (CSM), after radical local treatment (radical prostatectomy and/or radiotherapy) in men with high-risk prostate cancer. Medical records were reviewed for men with newly diagnosed high-risk prostate cancer who had pre-treatment 18F-choline positron emission tomography fused with computed tomography (PET/CT) scan for primary metastasis staging.ResultsOf 174 eligible men, 124 met the criteria for inclusion. The PET/CT scan was negative for metastasis in 97 (78%) men, inconclusive in 15 (12%), and positive in 12 (10%). The men with a positive PET/CT scan had significantly shorter time to BCR (p = 0.02), time to skeletal metastasis (p = 0.002), and time to prostate cancer specific death (p < 0.001). On multivariable Cox regression analysis, including also tumour stage, Gleason score, and PSA, a non-negative PET/CT scan was the only significant covariate for time to BCR (HR 2.6, 95% CI 1.3–5.5) and time to skeletal metastasis (HR 2.7, 95% CI 1.3–5.9).ConclusionsIn men with a newly diagnosed high-risk prostate cancer and a negative or inconclusive bone scan, 18F-choline uptake on PET/CT suggestive metastasis was associated with recurrence, progression to distant metastasis, and prostate cancer death. This strongly indicates that the choline uptakes represented metastasis and not false positive findings.

Prognostic value of selected preoperative inflammation-based scores in patients with high-risk localized prostate cancer who underwent radical prostatectomy.

BackgroundThis study investigated the prognostic value of inflammation-based scores in patients with high-risk localized prostate cancer who underwent radical prostatectomy with or without neoadjuvant androgen deprivation therapy (ADT).MethodsInflammation-based scores included the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and plasma fibrinogen. A total of 440 patients (380 patients treated without neoadjuvant ADT and 60 patients treated with neoadjuvant ADT) were retrospectively evaluated in our medical center. Receiver operating characteristic (ROC) curves and Kaplan–Meier analyses were performed to compare the prognostic value of these scores. Univariate and multivariate Cox regression analyses were also performed.ResultsFor all patients, dNLR and PNI were predictive of biochemical recurrence (.=0.041 and <0.001, respectively). Subgroup analysis of neoadjuvant strategies was also performed. For patients treated with neoadjuvant ADT, no selected inflammation-based scores were significantly correlated with biochemical recurrence (.>0.05). In contrast, for patients treated without neoadjuvant ADT, NLR (area under the ROC curve [AUC] =0.576, P=0.033), dNLR (.=0.585 and 0.017), PLR (AUC =0.582, P=0.024), and PNI (AUC =0.622, P<0.001) were predictive of biochemical recurrence. Kaplan–Meier analyses showed that dNLR (.=0.044), PLR (.=0.028), and PNI (.=0.004) were significantly associated with biochemical recurrence. Based on multivariable models, PNI was an independent predictor of biochemical recurrence (hazard ratio: 0.56, 95% confidence interval: 0.35–0.90, P=0.016).ConclusionHigh dNLR, high PLR, and low PNI were associated with poor biochemical recurrence-free survival in patients undergoing radical prostatectomy for high-risk localized prostate cancer not treated with neoadjuvant ADT. In particular, PNI was an independent prognostic factor for biochemical recurrence.

Abstract 1546: Low-molecular-weight protein tyrosine phosphatase is a useful biomarker for predicting postoperative biochemical recurrence in RM0 prostate cancer

Abstract Objective: Low-molecular-weight protein tyrosine phosphatase (LMPTP) has a molecular weight of 18 kDa. Studies have shown that the elevated expression of this enzyme is associated with poor prognosis of certain cancers. For prostate cancer, positive surgical margins are considered an important predictor of such recurrences. However, biochemical recurrence is observed even with a negative surgical margin (RM0), and some cases require salvage therapy. Few reports have identified useful biomarkers to predict these cases. In this study, we investigated whether LMPTP expression level could be a biomarker of these recurrences in RM0 prostate cancer. Methods: The subjects were 119 patients who underwent a total prostatectomy with a negative resection margin, at our hospital, between 2007 and 2011. Immunostaining of 2 TMA samples per patient was performed to evaluate LMPTP expression levels. Expression was classified as negative, 0; weak, 1; moderate, 2; or strong, 3 by two pathologists. Each patient was given a total expression score consisting of 13 levels from 0 to 12. By constructing a ROC curve, LMPTP expressions were categorized into either a high expression group (score: ≥5) or a low expression group (score: ≤4). We then examined the relationship of LMPTP expression level with other pathological observations and biochemical recurrence. Cancer survival analysis was performed using the Kaplan-Meier method, log-rank test, and Cox's proportional hazards model. The threshold for statistical significance was set at p &amp;lt; 0.05. Results: Evaluation of immunostained samples by the two pathologists were highly reliable, with an Intraclass correlation (ICC) score for two distinct measurements of 0.77 and 0.98, respectively. 68 patients (57.1%) were categorized in the LMPTP high expression group; and 51 patients (42.9%), in the low expression group. The log-rank test revealed that early biochemical recurrence was observed in the high LMPTP expression group (p = 0.0011). In addition, both the univariate and multivariate analyses revealed that high LMPTP expression level was an independent prognostic factor for biochemical recurrence. Furthermore, in the RM0 cases, high LMPTP expression level (HR:3.62, p = 0.023) was shown to be a better prognostic factor than Gleason score (GS; p = 0.406). Lastly, high LMPTP expression level strongly correlated with the Ki-67 proliferation marker (p &amp;lt; 0.0001), suggesting that LMPTP is expressed in tumor cells with high proliferative capacity. Conclusion: This study suggests that immunostaining of LMPTP is a better predictor of biochemical recurrence than GS in cases of RM0 total prostatectomy. This biomarker can be evaluated with a single immunostaining with high reproducibility, and can therefore be a clinically applicable tool in postoperative follow-ups and as a predictor of recurrence that require salvage therapy. Citation Format: Hirofumi Kurose, Kosuke Ueda, Reiichiro Kondo, Kiyoaki Nishihara, Makoto Nakiri, Mitsunori Matsuo, Shigetaka Suekane, Sakiko Sanada, Sachiko Ogasawara, Tsukasa Igawa, Hirohisa Yano. Low-molecular-weight protein tyrosine phosphatase is a useful biomarker for predicting postoperative biochemical recurrence in RM0 prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1546.

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: experience of a single center

Background: The purpose of this study was to report the outcomes and prognostic factors of patients who underwent salvage radiotherapy (SRT) for biochemical recurrence (BCR) following radical prostatectomy (RP) at a single center. Methods: We retrospectively reviewed 48 patients who underwent SRT for BCR after RP between January 2004 and December 2012. The Kaplan-Meier method and Cox proportional hazard regression models were used to evaluate the BCR-free survivals and the prognostic factors for BCR after SRT. Results: After a median follow-up of 68.7 months (range, 34.0–143.3 months). The BCR-free survival rates at 3 and 5 years for the 48 patients after SRT were 72.9% and 68.4%, respectively. Multivariate analysis showed that pre-RT PSA (prostate specific antigen) level >0.5 ng/mL, Gleason score at RP ≥8, and seminal vesicle invasion were significantly predictive of PSA relapse after SRT (HR: 23.29, 7.92, and 21.73). The BCR-free rate at 5 years in the pre-RT PSA level ≤0.5 and >0.5 ng/mL group was 83.4% and 52.2% (P=0.007), respectively. No grade 3 or worse acute adverse events were noted. Conclusions: SRT was an effective treatment for BCR following RP with tolerable toxicities. Lower pre-RT PSA value, low Gleason score, and non-seminal vesicle invasion were significant predictors of favorable biochemical outcomes. Our results supported the current recommendations that SRT should be initiated before PSA reaches 0.5 ng/mL.

Significance of prostate-specific antigen kinetics after three-dimensional conformal radiotherapy with androgen deprivation therapy in patients with localized prostate cancer.

To evaluate the relationship between biochemical recurrence and post-radiation prostate-specific antigen (PSA) kinetics in patients with localized prostate cancer treated by radiotherapy with various durations of androgen deprivation therapy (ADT). We reviewed our single-institution, retrospectively maintained data of 144 patients with T1c-T3N0M0 prostate cancer who underwent three-dimensional conformal radiotherapy (3D-CRT) between December 2005 and December 2015 and 113 patients were fulfilled the inclusion criteria. In this cohort, 3D-CRT was delivered with a dose in the range from 70.0 to 72.0Gy with ADT. All patients received ADT as concurrent regimens. Biochemical recurrence was defined on the basis of the following: "PSA nadir+2.0ng/ml or the clinical judgement of attending physicians". Kaplan-Meier, log-rank, and Cox regression analyses were carried out. The median follow-up period was 54.0months. The median duration of ADT was 17months (interquartile range, 10-24months). There was a trend toward statistical significant correlation between post-radiation PSA decline rate of≥90% and PSA recurrence (p=0.056). The same correlation could be observed in D'Amico high-risk patients (p=0.036). However, it was not observed between PSA nadir and PSA recurrence (p=0.40) in univariate analysis. Furthermore, multivariate analysis showed that post-radiation PSA decline rate of≥90% was a significant predictor of biochemical recurrence in patients who received radiotherapy with various durations of ADT (p=0.044). Post-radiation PSA decline rate of≥90% was a prognostic factor for biochemical recurrence in localized prostate cancer patients received 3D-CRT with various durations of ADT.

Complex evaluation of prognostic factors for biochemical recurrence after radical prostatectomy for patients with clinical locally advanced prostate cancer

Complex evaluation of prognostic factors for biochemical recurrence after radical prostatectomy for patients with clinical locally advanced prostate cancer

External beam radiation for the treatment of castration-resistant prostate cancer following primary hormonal therapy with androgen ablation: Analysis and outcome of 21 patients

Patients who undergo early androgen-deprivation therapy for prostate cancer may eventually develop castration-resistant prostate cancer. However, no optimal treatment for non-metastasized castration-resistant prostate cancer has yet been established. In the present retrospective, single-institutional study, the radiotherapy (RT) outcomes were evaluated in patients who underwent androgen-deprivation therapy for non-metastatic prostate cancer and subsequently developed castration-resistant disease. Following a thorough chart review, the data of 21 patients with castration-resistant prostate cancer who were treated between 2000 and 2010 with external beam radiation therapy (EBRT) at a prostate radiation dose of >45 Gy were evaluated. Of the 21 patients, 16 (76%) developed biochemical recurrence after RT, with a mean time to biochemical recurrence of 17 months. A total of 18 patients succumbed to the disease during follow-up, with a mean survival of 3 years after RT. A radiation dose of >66 Gy was associated with a longer time to biochemical recurrence after RT (P=0.011) and a longer survival, compared with a dose of ≤66 Gy (P=0.028). The mean overall survival time after RT was 42 months and did not depend on the primary hormonal treatment. Prostate-specific survival time was negatively associated with the Gleason score at diagnosis. The prostate-specific antigen (PSA) concentration prior to RT was a prognostic factor for biochemical recurrence of prostate cancer after RT, as well as for prostate cancer-specific survival. Finally, the multivariate analysis revealed that age, PSA concentration prior to RT and a high Gleason score were independent prognostic factors for prostate cancer-specific survival. Overall, our study findings demonstrated that disease progression was common after EBRT for castration-resistant prostate cancer and that survival was limited. However, young patients and those with low-risk disease at the time of diagnosis may benefit from RT.

Overexpression of Aquaporin-1 is a Prognostic Factor for Biochemical Recurrence in Prostate Adenocarcinoma.

Aquaporins (AQP) are transmembrane proteins that provide channels for water and solutes, and some are involved in tumor progression and invasion. We evaluated the expression of AQP-1, AQP-3, and AQP-5 and their clinicopathological significance in prostate adenocarcinomas (PCA). Prostatectomy specimens (n = 99) were retrieved from the surgical pathology archives and clinicopathological data were obtained from the medical database at Kyungpook National University Hospital. Immunohistochemical staining for AQP-1, AQP-3, and AQP-5 was performed on tissue microarrays comprising paired malignant and benign prostatic tissues. Seventeen PCA cases (17.2%) showed AQP-1 overexpression, specifically 7 tumors (9.7%) with lower Gleason scores (GS) and 10 tumors (37.0%) with higher GS, with statistical significance (P = 0.001). AQP-1 overexpression was significantly associated with higher GS (P = 0.001), higher pathologic T (pT) stages (P = 0.024), and biochemical recurrence (BR) (P = 0.002). The difference in AQP-3 and AQP-5 expression between neoplastic and non-neoplastic tissues was not established and there were no correlations with clinicopathological parameters. AQP-1 overexpression was evident in tumors with higher GS, it was less evident in tumors with lower GS, and it was associated with BR and a higher pT stage. AQP-1 overexpression is associated with prostate cancer progression.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy

ABSTRACTBiomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn.In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = −0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35–4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16–3.74], p = 0.014, n = 350).PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.

Overexpression of Pleomorphic Adenoma Gene-Like 2 Is a Novel Poor Prognostic Marker of Prostate Cancer.

Pleomorphic adenoma gene like-2 (PLAGL2) is a member of the PLAG gene family. Previous studies have revealed that overexpression of PLAGL2 is associated with many human cancers. However, it has been reported that PLAGL2 also plays as a tumor suppressor. The precise role of PLAGL2 in prostate cancer (PCa) is still unknown. The aim of this study was to investigate the expression and prognostic value of PLAGL2 in PCa. Data from microarray datasets demonstrated that the DNA copy number and mRNA level of PLAGL2 were significantly increased in PCa compared with normal prostate. qRT-PCR and western blot analysis from paired PCa samples and prostate cell lines confirmed upregulated mRNA and protein expression levels in PCa. Immunohistochemistry analysis showed that staining of PLAGL2 in PCa tissues was significantly higher than that in benign prostatic hyperplasia (BPH) tissues. In addition, the high expression of PLAGL2 was only involved in preoperative PSA, but was not related to age, Gleason score, seminal vesicle invasion, surgical margin status, clinical stage and positive lymph node metastasis. Moreover, our results showed that PLAGL2 was an independent prognostic factor for biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients, and overexpressed PLAGL2 was related to early development of BCR and poor OS. In conclusion, our findings suggest that PLAGL2 is overexpressed in PCa. The increased expression of PLAGL2 correlates to PCa progression following radical prostatectomy and may serve as a novel poor prognostic marker for PCa.

Prognostic Factors for Biochemical Recurrence More than 10 Years after Radical Prostatectomy

Some patients with long postoperative intervals of undetectable prostate specific antigen are still at risk for biochemical recurrence. Our aims were to identify prognostic factors for late biochemical recurrence, including cancer family history, and evaluate cancer specific mortality. We identified 10,310 patients after radical prostatectomy without neoadjuvant or adjuvant therapy between 1979 and 2015 in the prospective German Familial Prostate Cancer database. A subgroup of 2,480 patients with more than 10 years of followup (median 12.8) had undetectable prostate specific antigen. Biochemical recurrence, defined as prostate specific antigen 0.2 ng/ml or greater, developing at more than 10 years was defined as late biochemical recurrence. Multiple proportional hazards regression with forward selection was applied to determine prognostic factors for late biochemical recurrence. The Kaplan-Meier estimated biochemical recurrence rate at 10, 15 and 20 years was 34.3%, 44.0% and 52.7%, respectively. Of 2,480 patients with undetectable prostate specific antigen 10 years postoperatively 249 subsequently had biochemical recurrence, of whom 12 died of prostate cancer. The factors associated with late biochemical recurrence were age at surgery (HR 1.04 per year, p = 0.027), prostate specific antigen at diagnosis (HR 1.02 per ng/ml, p = 0.020), pathological Gleason score (categorical 2-6 vs 7 [3 + 4], 7, 7 [4 + 3] and 8-10, p=0.002) and pathological tumor stage pT3a or greater (HR 1.50, p = 0.065). From years 10 to 15 and 10 to 20 postoperatively the biochemical recurrence rate increased by 9.7% and 18.4%, respectively. In contrast to a family history of prostate cancer, age at surgery, prostate specific antigen at diagnosis, pathological tumor stage and pathological Gleason score were prognostic factors for late biochemical recurrence. Patients with late biochemical recurrence are still at risk for death from prostate cancer.

PSCA, Cox-2, and Ki-67 are independent, predictive markers of biochemical recurrence in clinically localized prostate cancer: a retrospective study.

Prostate cancer is the second most common male cancer, with half of all patients going on to develop metastases. To better identify patients at high risk for prostate cancer progression and reduce prostate cancer-related mortality, improved prognostic factors are required. In this study, we used immunohistochemistry (IHC) to determine the prognostic values of multiple tissue biomarkers in hormone-naοve prostatectomy specimens of prostate cancer. Using 510 prostatectomy specimens collected between 2002 and 2012, IHC analysis was performed for Cerb-2, Cyclin D1, VEGF, EGFR, Rb, PSCA, p53, Bcl-2, Cox-2, PMS2, and Ki-67 on formalin-fixed paraffin-embedded sections. The Cox proportional hazard model was used to determine the predictive risk factors for biochemical recurrence (BCR) of prostate cancer. During a median 44-month follow-up, 128 (25.1%) patients developed BCR. A multivariate regression analysis revealed that Ki-67 (hazard ratio [HR]: 1.60, P = 0.033), PSCA (HR: 0.42, P < 0.001), and Cox-2 (HR: 2.05, P = 0.003) were the only significant prognostic tissue markers of BCR. Resection margin status (HR: 1.67, P = 0.010), pathologic pT0/1/2 stage (vs pT3/4; HR: 0.20, P = 0.002), preoperative PSA levels (HR: 1.03, P < 0.001), biopsied (HR: 1.30, P = 0.022) and pathologic (HR: 1.42, P = 0.005) Gleason scores, and prostate size (HR: 0.97, P = 0.003) were significant clinicopathologic factors. The expression of Ki-67, PSCA, and Cox-2 biomarkers along with other clinicopathologic factors were prognostic factors for BCR in patients with clinically localized prostate cancer following radical prostatectomy.

Long non-coding RNA ATB promotes growth and epithelial-mesenchymal transition and predicts poor prognosis in human prostate carcinoma.

Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-β (lncRNA-ATB) is a stimulator of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways.

Characteristics of Anteriorly Located Prostate Cancer and the Usefulness of Multiparametric Magnetic Resonance Imaging for Diagnosis

We analyzed the pathological and oncologic characteristics of anteriorly located prostate cancer and assessed the usefulness of magnetic resonance imaging to detect anterior prostate cancer. We analyzed the records of 728 consecutive patients treated with radical prostatectomy. Patients were categorized with anterior or prostate cancer or tumors involving the anterior and posterior prostate according to the dominant tumor location on whole mount section. The anterior and posterior prostate cancer groups and the group with cancer at both locations represented 31.0%, 46.7% and 22.3% of the total number of patients, respectively. Anterior prostate cancer was less commonly palpable (p<0.001) and needed more frequent repeat biopsy (p = 0.012) than posterior prostate cancer. Moreover, the anterior group had fewer positive cores than the posterior group (p <0.001) despite comparable tumor volumes. Gleason score upgrading was more frequently observed in anterior than in posterior prostate cancer (p = 0.003). However, final pathological features did not significantly differ. Only the seminal vesicle involvement rate was lower in anterior than in posterior prostate cancer (p <0.001). Estimated 5-year biochemical recurrence-free survival in patients with anterior prostate cancer was 87.5%, significantly higher than in patients with posterior prostate cancer (77.4%, p = 0.001) and patients with anterior plus posterior involvement (74.4%, p <0.001). Multivariate analysis revealed that anterior location was an independent prognostic factor for biochemical recurrence (HR 0.403) along with other well-known prognostic factors. To detect anterior prostate tumors the sensitivity and specificity of magnetic resonance imaging were 78.1% and 58.2%, respectively. Anterior prostate cancer had pathological features and favorable oncologic outcomes comparable to those of posterior prostate cancer but also more frequent Gleason score upgrading. Magnetic resonance imaging had moderate diagnostic performance for detecting lesions in the anterior prostate.

Validation of lymphovascular invasion is an independent prognostic factor for biochemical recurrence after radical prostatectomy

ObjectiveTo validate the impact of lymphovascular invasion (LVI) on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) in a large multiinstitutional cohort. Material and methodsRetrospective data from 6,678 patients treated with a RP and bilateral lymphadenectomy for prostate cancer (PC) from 8 centers were collected. The primary endpoint was BCR. ResultsOverall, 767 patients (11.5%) had LVI. Patients with LVI had significantly higher Gleason scores (P = 0.01). After a median follow-up of 28 months (interquartile range: 21–44), patients with LVI had a 1.66 fold increased risk of BCR (P<0.001). The 1-, 2- and 5-year biochemical recurrence-free survival probabilities for LVI vs. no LVI were 94% vs. 97%, 91% vs. 94%, and 76% vs. 84%, respectively. On multivariable analysis that adjusted for the effects of established prognostic factors, LVI was an independent predictor of BCR (hazard ratio = 1.42, P<0.001). Adding LVI to a multivariable base model increased the discrimination by a small but significant margin (+0.2%, P = 0.0005). In subgroup analyses, LVI remained an independent predictor for BCR in patients with worse pathological features. ConclusionsAbout 10% of patients with localized PC have LVI on their RP specimen. We confirm that LVI is associated with features of biologic aggressive PC such as high Gleason grade and BCR after RP. Adverse further studies with strict definitions of LVI and longer follow-up periods are needed to determine the prognostic and predictive utility of LVI in the management of PC.

The association between metabolic syndrome and prostate cancer: Effect on cancer aggressiveness and progression

ObjectivesTo evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. Materials and methodsAn observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression. ResultsOf the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% versus 18%; p=.002). Poorer results were found in the radical prostatectomy specimens (Gleason score≥7, p<.001; stage≥T2c, p<.001; positive surgical margins, p<.001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% versus 13%; p=.003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score≥7 for the specimen, as well as for finding a specimen stage≥T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, p<.001; OR: 3.2, p=.03; HR: 1.7; respectively). ConclusionsMetabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence.

Asociación entre síndrome metabólico y cáncer de próstata: efecto sobre su agresividad y progresión

ObjectivesTo evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. Material and methodsAn observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression. ResultsOf the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% vs. 18%; P=.002). Poorer results were found in the radical prostatectomy specimens (Gleason score ≥7, P<.001; stage≥T2c, P<.001; positive surgical margins, P<.001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% vs. 13%; P=.003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score ≥7 for the specimen, as well as for finding a specimen stage ≥T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, P<.001; OR: 3.2, P=.03; HR: 1.7; respectively). ConclusionsMetabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence.

Prediction of biochemical recurrence after robot-assisted radical prostatectomy: analysis of 784 Japanese patients.

To examine biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients, and to develop a risk stratification model for biochemical recurrence. The study cohort consisted of 784 patients with localized prostate cancer who underwent robot-assisted radical prostatectomy without neoadjuvant or adjuvant endocrine therapy. The relationships of biochemical recurrence with perioperative findings were evaluated. The prognostic factors for biochemical recurrence-free survival were evaluated using Cox proportional hazard model analyses. During the follow-up period, 80 patients showed biochemical recurrence. The biochemical recurrence-free survival rates at 1, 3, and 5 years were 92.2%, 85.2% and 80.1%, respectively. In univariate analysis, the prostate-specific antigen level, prostate-specific antigen density, biopsy Gleason score, percent positive core, pathological T stage, pathological Gleason score, lymphovascular invasion, perineural invasion and positive surgical margin were significantly associated with biochemical recurrence. In multivariate analysis, prostate-specific antigen density ≥0.4 (P = 0.0011), pathological T stage ≥3a (P = 0.002), pathological Gleason score ≥8 (P = 0.007) and positive surgical margin (P < 0.0001) were independent predictors of biochemical recurrence. The patients were stratified into three risk groups according to these factors. The 5-year biochemical recurrence-free survival rate was 89.4% in the low-risk group, 65.6% in the intermediate-risk group and 30.3% in the high-risk group. The prostate-specific antigen density, pathological T stage, pathological Gleason score and positive surgical margin were independent prognostic factors for biochemical recurrence. The risk stratification model developed using these four factors could help clinicians identify patients with a poor prognosis who might be good candidates for clinical trials of alternative management strategies.

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population.

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.