Prognostic Factor For Biochemical Recurrence Research Articles

The effect of surgical margin features on oncologic outcomes after radical prostatectomy

BackgroundEvaluation of the effect of additional surgical margin parameters on biochemical recurrence (BCR) in patients with positive surgical margins (PSM) after radical prostatectomy (RP).MethodsClinicopathological and outcome data from 91 patients with PSM who underwent RP were retrospectively analyzed. Additional surgical margin parameters (PSM length, highest Gleason grade (GG), localization of PSM (apex, bladder neck, or posterolateral), and unifocality or multifocality) were examined and their effects on BCR were investigated.ResultsFifty patients with PSM were included in the study. The mean age of the patients was 63.6 ± 6.9 years. The laparoscopic approach was undertaken more frequently, used for 36 (72%) patients compared to open RP performed in 14 cases (28%). The median follow-up time was 57.0 months (24.0–125.0 months). BCR developed in 14 (28%) patients during the follow-up period. Although mean BCR-free survival was shorter in cases with PSM length ≥ 3 mm compared to those with PSM length < 3 mm (90.4 vs. 108.2 months), multifocality compared to those with unifocality (62 vs. 97.4 months) and surgical margin GG ≥ 4 compared to those with GG 3 (87.4 vs. 97.5 months), the differences were not statistically significant (p = 0.251, p = 0.509 and p = 0.317, respectively). In addition, none of the PSM localizations affected BCR-free survival (p = 0.619). In univariate Cox regression analysis, PSM length affected BCR at a level close to statistical significance (HR = 1.16; p = 0.052). In multiple Cox regression analysis, main tumor Gleason score was determined to be a risk factor associated with BCR (HR = 4.75; p = 0.041).ConclusionsAlthough BCR-free survival was shortened in the presence of poor prognostic features (multifocal PSM, PSM length ≥ 3 mm, surgical margin GG ≥ 4) at the surgical margin, none of these parameters affected BCR at a statistically significant level. Gleason score of the main tumor was found to be a better prognostic factor for BCR.

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

Local dose (biologically effective dose ≥180 Gy2) is an important predictor of biochemical recurrence in patients undergoing low-dose-rate brachytherapy.

To evaluate prognostic factors of biochemical recurrence (BCR) in each risk group of prostate cancer patients who underwent low-dose-rate brachytherapy (LDR-BT). A total of 944 patients with clinically confirmed prostate cancer (cT1c-3aN0M0) who had underwent LDR-BT were enrolled. The low-, intermediate-, and high-risk groups included 278, 498, and 168 patients, respectively. The median age, PSA value at diagnosis, and the follow-up period were 70 years (range: 48-84), 7.2 ng/ml (range: 1.2-113), and 91 months (range: 2-192), respectively. We evaluated the BCR-free rate, BCR-free survival, clinical recurrence-free rate, overall survival (OS), and cancer-specific survival (CSS). We conducted multivariate analysis to elucidate prognostic factors of BCR for all patients and for each risk group. The 5- and 10-year OS rates were 96.0% and 89.5% and the 5- and 10-year CSS rates were 99.8% and 99.1%, respectively, while the 5- and 10-year BCR-free rates were 96.6% and 92.5% in low-risk patients, 95.7% and 90.7% in intermediate-risk patients and 93.8% and 89.0% in high-risk patients, respectively. There were no significant differences between the risk groups. Age-adjusted multivariate analysis indicated biologically effective dose (BED) <180 Gy2 as an independent prognostic factor of BCR in all patients (p = 0.005). There were no independent factors in the low- and high-risk groups, but neoadjuvant androgen deprivation therapy (ADT) (p = 0.022) and BED <180Gy2 (p = 0.042) were independent prognostic factors in the intermediate-risk group. LDR-BT can achieve a higher recurrence-free survival with an adequate local radiation dose (BED ≥ 180 Gy2).

A Novel Angiogenesis-Related Gene Signature to Predict Biochemical Recurrence of Patients with Prostate Cancer following Radical Therapy

Background Prostate cancer (PCa) is one of the most common malignancies in males; we aim to establish a novel angiogenesis-related gene signature for biochemical recurrence (BCR) prediction in PCa patients following radical therapy. Methods Gene expression profiles and corresponding clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We quantified the levels of various cancer hallmarks and identified angiogenesis as the primary risk factor for BCR. Then machine learning methods combined with Cox regression analysis were used to screen prognostic genes and construct an angiogenesis-related gene signature, which was further verified in external cohorts. Furthermore, estimation of immune cell abundance and prediction of drug responses were also conducted to detect potential mechanisms. Results Angiogenesis was regarded as the leading risk factor for BCR in PCa patients (HR = 1.58, 95% CI: 1.38–1.81), and a novel prognostic signature based on three genes (NRP1, JAG2, and VCAN) was developed in the training cohort and successfully validated in another three independent cohorts. In all datasets, this signature was identified as a prognostic factor with promising and robust predictive values. Moreover, it also predicted higher infiltration of regulatory T cells and M2-polarized macrophages and increased drug sensitivity of angiogenesis inhibitors in high-risk patients. Conclusions The angiogenesis-related three-gene signature may serve as an independent prognostic factor for BCR, which would contribute to risk stratification and personalized management of PCa patients after radical therapy in clinical practice.

Obesity and biochemical recurrence in clinically localised prostate cancer: a systematic review and meta-analysis of 86,490 patients.

The association of obesity with biochemical recurrence (BCR) after treatment of clinically localised prostate cancer (PC) shows inconsistent results. Our aim was to systematically review all evidence evaluating obesity as a prognostic factor for BCR. We searched PubMed, Web of Science and Scopus, from inception to June 1, 2021. Cohort studies reporting BCR among PC patients stratified by body mass index (BMI) were included. To assess the quality of the selected studies, we used the Newcastle-Ottawa scale (NOS). Risk of BCR among obese patients (BMI ≥ 30 kg/m2) was compared with normal weight (BMI < 25), pooling individual hazard ratios (HR) in random-effect meta-analysis. Associations for continuous BMI per 5 kg/m2 were also calculated. Subgroup analyses were conducted to assess reasons for heterogeneity and causal criteria were formally evaluated. We identified 46 cohort studies including 86,490 PC patients. A total of 14,719 (17.1%) patients developed BCR. There was no consistent definition of BCR. Obesity was associated with BCR (HR: 1.25, 95% CI: 1.11-1.39, I2: 70.3%), and there was a 10% increase (95% CI: 4-15%, I2: 66.3%) in BCR per 5 kg/m2 increase in BMI. The heterogeneity was high but decreased in the subgroup of highest-quality NOS score and when the BMI was measured by the researchers (I2: 0.0%). The association was consistent in patients receiving radical prostatectomy but not in patients receiving other therapies. Obesity showed a moderate, consistent relationship with biochemical recurrence after radical prostatectomy. Measurement of BMI and BCR was variable, highlighting the need for standardised clinical guidelines. Preventive weight control programs may have a role in reducing BCR for clinically localised PC patients.

Overweight and obesity as risk factors for biochemical recurrence of prostate cancer after radical prostatectomy.

Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for "normal" (< 23kg/m2), "overweight" (23-27.5kg/m2), and "obese" (≥ 27.5kg/m2). Among the 389 patients included in this study, 108 were classified as normal, while 227 and 54 patients were classified as overweight and obese, respectively. The relationships between clinicopathological factors and biochemical recurrence were analyzed by univariate and multivariate Cox ≤ proportional hazard models. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) measurements ≥ 0.2ng/mL. In univariate analysis, the categorical variables of "overweight" and "obese" were significant prognostic factors for biochemical recurrence. In multivariate analysis models including PSA density [hazard ratio (HR) 1.8, p = 0.01], extraprostatic extension (HR 2.0, p < 0.001), Gleason score (HR 1.7, p = 0.01), surgical margin positivity (HR 2.46, p < 0.001), and lymphovascular invasion (HR 2.53, p < 0.001), the categorical variables of "overweight" (HR 1.6, p = 0.03) and "obese" (HR 1.76, p = 0.035) were prognostic factors for biochemical recurrence. The obesity status of patients with prostate cancer as "overweight" and "obese" was a risk factor for biochemical recurrence after adjusting for other clinicopathological factors.

Dose-Based Radiomic Analysis (Dosiomics) for Intensity Modulated Radiation Therapy in Patients With Prostate Cancer: Correlation Between Planned Dose Distribution and Biochemical Failure

Although radiation therapy is one of the most significant treatment modalities for localized prostate cancer, the prognostic factors for biochemical recurrence (BCR) regarding the treatment plan are unclear. We aimed to develop a novel dosiomics-based prediction model for BCR in patients with prostate cancer and clarify the correlations between the dosimetric factors and BCR. This study included 489 patients with localized prostate cancer (BCR: 96; no-BCR: 393) who received intensity modulated radiation therapy. A total of 2475 dosiomic features were extracted from the dose distributions on the prostate, clinical target volume (CTV), and planning target volume. A prediction model for BCR was trained on a training cohort of 342 patients. The performance of this model was validated using the concordance index (C-index) in a validation cohort of 147 patients. Another model was constructed using clinical variables, dosimetric parameters, and radiomic features for comparisons. Kaplan-Meier curves with log-rank analysis were used to assess the univariate discrimination based on the predictive dosiomic features. The dosiomic feature derived from the CTV was significantly associated with BCR (hazard ratio, 0.73; 95% CI, 0.57-0.93; P=.01). Although the dosiomics model outperformed the dosimetric and radiomics models, it did not outperform the clinical model. The performance significantly improved by combining the clinical variables and dosiomic features (C-index: 0.67; 95% CI, 0.65-0.68; P < .0001). The predictive dosiomic features were used to distinguish high-risk and low-risk patients (P < .05). The dosiomic feature extracted from the CTV was significantly correlated with BCR in patients with prostate cancer, and the dosiomics model outperformed the model with conventional dose indices. Hence, new metrics for evaluating the quality of a treatment plan are warranted. Moreover, further research should be conducted to determine whether dosiomics can be incorporated in a clinical workflow or clinical trial.

Autophagy-related circRNA evaluation reveals hsa_circ_0001747 as a potential favorable prognostic factor for biochemical recurrence in patients with prostate cancer

Prostate cancer (PCa) is a common high-incidence malignancy in men, some of whom develop biochemical recurrence (BCR) in the advanced stage. However, there are currently no accurate prognostic indicators of BCR in PCa. The aim of our study was to identify an autophagy-related circular RNA prognostic factor of BCR for patients with PCa. In this study, immunochemistry revealed that the classic autophagy marker MAP1LC3B was positively correlated with Gleason score. Least absolute shrinkage and selector operator regression were conducted to develop a novel prognostic model with tenfold cross-validation and an L1 penalty. Five autophagy-related circRNA signatures were included in the prognostic model. Patients with PCa were ultimately divided into high- and low-risk groups, based on the median risk score. Patients with PCa, who had a high risk score, were more likely to develop BCR in a shorter period of time. Univariate and multivariate Cox regression analyses demonstrated that the risk score was an independent variable for predicting BCR in PCa. In addition, a prognostic nomogram integrated with the risk score and numerous clinicopathological parameters was developed to accurately predict 3- and 5-year BCR of patients with PCa. Finally, the hsa_circ_0001747 signature was selected for further experimental verification in vitro and in vivo, which showed that downregulated hsa_circ_0001747 might facilitate PCa via augmenting autophagy. Our findings indicate that the autophagy-related circRNA signature hsa_circ_0001747 may serve as a promising indicator for BCR prediction in patients with PCa.

Evaluation of circulating β2-microglobulin as a prognostic factor for biochemical recurrence after radical prostatectomy

Objectives: One of the most challenging issues after radical prostatectomy (RP) is biochemical recurrence (BCR). The prediction of BCR can determine the selection of modality and its continuation. Currently, preoperative PSA level, Gleason score, and stage of tumor are used for prediction of BCR. The association of β2-microglobulin (B2MG) with hematologic and solid tumors, such as prostate cancer, was suggested in previous studies. The circulating B2MG, as a risk factor for BCR, has been applied for the first time in the current study. Circulating B2MG likely provides a good environment for the growth of cancer cells due to its angiogenesis and tumorigenesis properties. Methods and materials: A cohort study of 59 patients who underwent RP from 2012 to 2013 was carried out. B2MG was measured in the stored serum samples taken from the patients who underwent biopsy. Patients were monitored for BCR and metastasis caused by prostate cancer over a five-year period. The association of B2MG level with the PSA rising were investigated using multivariate models by adjustment for age, PSA, and Gleason's score effects. Results: Mean concentration of B2MG varied significantly according to patient age, PSA, and Gleason's score. One unit increase in the B2MG may significantly increase the hazard of PSA rising (HR=2.528; 95% CI 1.101–5.319; p-value=0.015). Hazard of PSA rising in high-risk groups was a 2.543-fold increase with a unit increase in B2MG. Conclusion: B2MG could help identify those who would derive the greatest benefit from additional systemic or local treatment. Level of evidence: Not applicable for this multicentre audit.

Contrast-enhanced transrectal ultrasound can reduce collection of unnecessary biopsies when diagnosing prostate cancer and is predictive of biochemical recurrence following a radical prostatectomy in patients with localized prostate cancer

BackgroundTo investigate the value of using contrast-enhanced transrectal ultrasound (CETRUS) to reduce unnecessary collection of biopsies during prostate cancer diagnosis and its utility in predicting biochemical recurrence in patients with localized prostate cancer.MethodsThis was a prospective study of suspected prostate cancer patients who were evaluated with CETRUS followed by a prostate biopsy. Prostate blood flow via CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcome was then analyzed for all patients; univariate and multi-variate analyses were used to determine the probable prognostic factors for biochemical recurrence in patients with localized prostate cancer that underwent a radical prostatectomy.ResultsA total of 347 patients were enrolled in the study. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer incidence. Using CETRUS scores ≥2 as the threshold for when to biopsy could have safely reduced the number of biopsies taken overall by 12.1% (42/347) and spared 23.0% (42/183) of patients from undergoing an unnecessary biopsy. 77 patients with localized prostate cancer underwent a radical prostatectomy. The median follow-up time was 30 months (range: 8–56 months) and 17 of these 77 patients exhibited biochemical recurrence during the follow-up period. 3-year biochemical recurrence-free survival rates were 86% for patients with low CETRUS scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis indicated that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00–24.69; p = 0.002).ConclusionsCETRUS scores may be a useful tool for reducing the collection unnecessary biopsy samples during prostate cancer diagnosis and are predictive of biochemical recurrence in patients with localized prostate cancer following a radical prostatectomy.

Small-volume lymph node involvement and biochemical recurrence after robot-assisted radical prostatectomy with extended lymph node dissection in prostate cancer.

We investigated prognostic factors for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node (LN) dissection. We included 173 patients who underwent RARP with extended pelvic LN dissection without neoadjuvant therapy at our hospital between October 2010 and April 2018. BCR was defined as prostate serum antigen (PSA) levels ≥ 0.2ng/mL; BCR-free survival rates were determined using Kaplan-Meier analysis. We used Cox regression analysis to evaluate effects of PSA and pathologic variables on BCR. Median follow-up was 27.9 (range 6.1-86.9) months. Five-year BCR-free survival was 89.5%. In multivariate analysis, positive LNs (HR 7.117; 95% CI 2.826-17.925; P < 0.001) and Gleason score (GS) ≥ 8 (HR 2.612; 95% CI 1.051-6.489; P = 0.039) were significant predictors of BCR. Patients with 1 or 2 positive LNs (n = 10) had significantly higher BCR-free survival rates than patients with ≥ 3 positive LNs (n = 5). We, therefore, stratified the patients as low-risk (GS < 8 and no positive LNs), intermediate-risk: (either GS ≥ 8 or positive LNs) and high-risk (both GS ≥ 8 and positive LNs). Their 1-year BCR-free survival rates were low-risk: 94.6%, intermediate-risk: 88.5%, and high-risk: 33.3% (P < 0.05). Patients with 1-2 positive LNs and GS < 8 have low risk for BCR; close observation without immediate adjuvant hormonal therapy can be considered for these patients.

Percent tumor volume vs American Joint Committee on Cancer staging system subclassification for predicting biochemical recurrence in patients with pathologic T2 prostate cancer

Here, we re-checked the American Joint Committee on Cancer 7th edition subclassification and confirmed the possibility of percent tumor volume as a prognostic factor for biochemical recurrence in the 8th edition subclassification. A total of 1073 patients with pathologic T2 stage disease who underwent radical prostatectomy were included. Exclusion criteria were neoadjuvant therapy and pathologic T3 and N1 disease. Biochemical recurrence-free survival was estimated using the Kaplan-Meier method. Cox hazard regression was used to predict biochemical recurrence. According to the 7th edition subclassification, 141 patients (13.1%) had T2a, 43 (4.0%) had T2b, and 889 (82.9%) had T2c disease. The 7th edition subclassification did not differ significantly on Kaplan-Meier analysis (p = 0.502). Mean percent tumor volume was 8.7 ± 8.0% (interquartile range, 5-10%). Percent tumor volume was positively correlated with initial prostate-specific antigen, grade group, surgical margin, and T2 subclassification (all p < 0.001). The 7th edition subclassification was not a significant factor, whereas percent tumor volume was (hazard ratio, 1.023; 95% confidence interval, 1.005-1.041; p = 0.0128) on multivariate analysis. On Kaplan-Meier analysis, percent tumor volume (> 7.5% vs ≤ 7.5%) differed significantly for biochemical recurrence-free survival (p < 0.001). The 7th edition pathologic T2 subclassification had poor prognostic value for biochemical recurrence in our cohort. Elimination of the 8th edition subclassification was suitable. Percent tumor volume classified biochemical recurrence prognosis in pathologic T2 stage. Therefore, percent tumor volume can be a candidate factor for the next T2 subclassification.

Targeted next-generation sequencing for locally advanced prostate cancer in the Korean population.

PurposeThis study aimed to evaluate the feasibility of pan-cancer panel analysis for locally advanced prostate cancer in the Korean population.Materials and MethodsWe analyzed 20 patients with locally advanced prostate cancer who underwent radical prostatectomy. A pan-cancer panel (1.9 Mbp) developed by Seoul National University Hospital (SNUH), composed of 183 target genes, 23 fusion genes, and 45 drug target regions was used for this analysis. We compared the SNUH pan-cancer panel results with The Cancer Genome Atlas (TCGA) database to search for different mutations in the Korean population. Clinical data were analyzed with univariate and multivariate analysis, and p-values <0.05 were considered statistically significant. Kaplan–Meier curve and log-rank tests were performed to evaluate survival.ResultsThe average age of the patients and initial prostate-specific antigen values were 69.3±7.8 years and 66.3±16.9 ng/dL, respectively. Average sequencing depth was 574.5±304.1×. Ninety-nine genetic mutations and 5 fusions were detected. SPOP (25%), KMT2D (20%), and BRAF (15%) were frequently detected. ERG fusions were recurrently detected in 20% of the patients, with SLMAP and SETD4 as novel fusion partners. BRAF mutation was frequently detected in this study, but not in the TCGA database. Multivariate analysis showed BRAF mutation as an independent prognostic factor for biochemical recurrence (hazard ratio, 9.84; p=0.03).ConclusionsThe pan-cancer panel comprising genes related to prostate cancer is a useful tool for evaluating genetic alterations in locally advanced prostate cancers. Our results suggest that the BRAF mutation is associated with biochemical recurrence in the Korean population.

Elevated Expression of EPHA2 Is Associated With Poor Prognosis After Radical Prostatectomy in Prostate Cancer.

Therapeutic targeting of receptor protein tyrosine kinases (PTKs) has proven successful in treating cancer. However, reports about PTKs in treating prostate cancer are few. Elevated expression of the erythropoietin-producing hepatocellular receptor A2 (EPHA2) receptor tyrosine kinase, a transmembrane protein, is associated with poor prognosis of certain cancer types when the enzyme is dephosphorylated. This study investigated whether EPHA2 is useful in predicting the biochemical recurrence of prostate cancer. Data from 241 patients who had undergone total prostatectomy between 2007 and 2011 were used. EPHA2 protein expression was categorized as high or low by two pathologists. The relationship was examined between EPHA2 expression level (high vs. low) and clinicopathological factors including biochemical recurrence. Correlations were examined between EPHA2, low-molecular-weight protein tyrosine phosphatase (LMW-PTP), E-cadherin, and Ki-67. EPHA2 expression was high in 121 (50.2%) and low in 120 (49.8%) patients. A log-rank test revealed early biochemical recurrence in the high-expression group. Gleason score, Ki-67 labeling index, and biochemical recurrence were more frequent in the high-expression group. Furthermore, multivariate analyses revealed that high EPHA2 expression was an independent prognostic factor for biochemical recurrence (hazard ratio=3.62, 95% confidence interval=2.39-5.61). Correlations between EPHA2 and both LMW-PTP and Ki-67 labeling index were positive, whereas EPHA2 and E-cadherin were negatively correlated. EPHA2 overexpression is predictive of aggressive prostate cancer behavior. EPHA2 may be a powerful prognostic biomarker for decision-making in postoperative follow-up after total prostatectomy, and regarding the need for palliative treatment. Additionally, it may be an important therapeutic target.

The significance of micro-lymphatic invasion and pathological Gleason score in prostate cancer patients with pathologically organ-confined disease and negative surgical margins after robot-assisted radical prostatectomy.

The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.

Salvage reirradiation for local prostate cancer recurrence after radiation therapy. For who? When? How?

PurposeLiterature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. Materials and methodsA total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy. ResultsLate genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. ConclusionDespite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.

Gleason Pattern 5 is a Possible Pathologic Predictor for Biochemical Recurrence after Laparoscopic Radical Prostatectomy

Objective:Several prognostic factors for biochemical recurrence after radical prostatectomy have been reported, including initial prostate-specific antigen level, Gleason score, positive surgical margin, and seminal vesicle invasion. Here we investigate whether Gleason pattern 5 is a predictor for biochemical recurrence.Methods:This retrospective study included 168 patients who underwent laparoscopic radical prostatectomy from 2006 to 2015. The relationship between biochemical recurrence after laparoscopic radical prostatectomy and the presence of Gleason pattern 5, even as a tertiary pattern, was investigated. Biochemical recurrence was defined when the prostate-specific antigen level rose to >0.2 ng/ml after having decreased to <0.1 ng/ml following laparoscopic radical prostatectomy. Biochemical recurrence-free survival was estimated by the Kaplan-Meier method. Multivariate analysis was performed using a Cox proportional hazards regression model.Results:The median age was 66 years, median initial prostate-specific antigen level was 6.9 ng/ml, and median follow-up period was 47.3 months. Biochemical recurrence was recognized in 27 patients (16.1%) after laparoscopic radical prostatectomy, and 5-year biochemical recurrence-free survival was 78.6%. Gleason pattern 5 was noted in 5 patients as the primary pattern, in 10 as the secondary pattern, and in 5 as the tertiary pattern. According to multivariate analysis, presence of Gleason pattern 5 (HR = 4.75, p=0.001) and positive surgical margin (HR = 4.66, p=0.001) were independent predictive factors for biochemical recurrence-free survival.Conclusion:Gleason pattern 5 appears to be an important predictive factor for biochemical recurrence after laparoscopic radical prostatectomy.

Low-molecular-weight Protein Tyrosine Phosphatase Is a Possible Biomarker for Predicting Postoperative Biochemical Recurrence in Prostate Cancer With Negative Surgical Margins.

For prostate cancer, positive surgical margins are considered an important predictor of biochemical recurrence. However, biochemical recurrence is observed in approximately 20% of cases, even with negative surgical margins, and some cases require salvage therapy. The elevated expression of low-molecular-weight protein tyrosine phosphatase (LMW-PTP, MW 18 kDa) is associated with a poor prognosis of certain cancers. In this study, we investigated whether the LMW-PTP expression levels could be used as a biomarker of recurrence in prostate cancer with negative surgical margins. The subjects of this retrospective study were 119 patients who underwent total prostatectomy with negative resection margins. LMW-PTP expression was categorized either as a high-expression group or as a low-expression group bye two pathologists. Subsequently, we examined the relationship between LMW-PTP expression levels and clinicopathological factors including biochemical recurrence. Evaluation of the immunostained samples by two pathologists was highly reliable, with an Intraclass correlation (ICC) score for two distinct measurements of 0.77 and 0.98, respectively. Seventy-three patients (61.3%) were placed in the LMW-PTP high expression group; and 46 patients (38.7%) were placed in the low expression group. The log-rank test revealed early biochemical recurrence in the high LMW-PTP expression group (p=0.0001). In addition, pathological T stage (p=0.004), lymphatic invasion (p=0.0456), Ki-67 labeling index (p=0.0002), and biochemical recurrence (p<0.0001) were more frequently identified in the LMW-PTP high expression group. Furthermore, multivariate analyses revealed that a high LMW-PTP expression level was an independent prognostic factor for biochemical recurrence (HR=3.14, 95% CI=1.37-8.07, p=0.0057). In addition, Ki-67 labeling indices were significantly higher in the high-expression group compared to the low-expression group (p<0.0001). LMW-PTP can be assessed using a single immunostaining protocol in a highly reproducible fashion. Tt may, thus, be applied clinically to establish the required postoperative follow-up period and determine the necessity for salvage therapy in cases of prostate cancer with negative surgical margins. LMW-PTP has the potential to be a highly useful prognostic biomarker and a therapeutic target in conjunction with other factors, such as the Gleason Score, the pathological T stage and the PSA level.

High sulfite oxidase expression could predict postoperative biochemical recurrence in patients with prostate cancer.

Sulfite oxidase (SUOX) is a metalloenzyme that plays a role in ATP synthesis via oxidative phosphorylation in mitochondria and has been reported to also be involved in the invasion and differentiation capacities of tumor cells. Here, we performed a clinicopathological investigation of SUOX expression in prostate cancer and discussed the usefulness of SUOX expression as a predictor of biochemical recurrence following surgical treatment in prostate cancer. This study was conducted using Tissue Micro Array specimens obtained from 97 patients who underwent radical prostatectomy at our hospital between 2007 and 2011. SUOX staining was used to evaluate cytoplasmic SUOX expression. In the high-expression group, the early biochemical recurrence was significantly more frequent than in the low-expression group (p = 0.0008). In multivariate analysis, high SUOX expression was found to serve as an independent prognostic factor of biochemical recurrence (hazard ratio = 2.33, 95% confidence interval = 1.32-4.15, p = 0.0037). In addition, Ki-67-labeling indices were significantly higher in the high-expression group than in the low-expression group (p = 0.0058). Therefore, SUOX expression may be a powerful prognostic biomarker for decision-making in postoperative follow-up after total prostatectomy and with regard to the need for relief treatment.

The impact of single positive surgical margin features on biochemical recurrence after robotic radical prostatectomy.

ABSTRACTObjective:Parameters predictive of biochemical or clinical recurrence after Radical Prostatectomy (RP) were determined as pre-treatment PSA value, pathologic tumor stage, tumor grade and presence of Positive Surgical Margin (PSM), extracapsular extension and seminal vesicle invasion and the status of pelvic lymph nodes. The aim of our study is to evaluate the effect of additional features in patients undergoing RP in our clinic.Materials and Methods:We studied 556 RP operations performed between 2009 and 2016 for prostate cancer at this clinic. Preoperative and postoperative data of the patients were retrospectively reviewed. RP specimens were examined by two pathologists specialized in this subject. Of these patients, 78 (14.02%) patients with PSM were included in the study. The pathology slides of these patients were reassessed. The length of PSM (mm), localization (apex, basis and posterolateral) and Gleason pattern at this margin was determined and statistical correlations with BCR were calculated.Results:The mean follow-up after the RP of 41 patients included in the study was 37.4 ± 13.2 months. During the follow-up period of the patients, BCR was observed in 16 patients (39.02%). No statistically significant difference was observed in age and prostate volume between the groups with and without BCR development (p > 0.05). Preoperative PSA level was found to be statistically significantly higher in the group with BCR development compared to the group without recurrence (p = 0.004). In-group comparisons in each aforementioned Gleason score groups were performed in terms of BCR development and the preoperative Gleason score in the group with development of recurrence was found to be statistically significantly higher compared to the group without recurrence (p = 0.007). The length of the surgical margin was measured as 7.4 ± 4.4 mm in the BCR-developing group and 4.7 ± 3.8 mm in the no-BCR- developing group; it was statistically significantly higher in the group with development of recurrence (p = 0.03).Conclusion:Length and location of the PSM and the Gleason score detected in the PSM region could not predict biochemical recurrence according to the results of this present study. However high preoperative PSA value is an independent prognostic factor for biochemical recurrence.