Risk Of Early Biochemical Recurrence Research Articles

Prognostic significance of PI-RADS 5 lesions in patients treated by radical prostatectomy.

To analyse the pathological features and survival of patients with a PI-RADS 5 lesion on pre-biopsy MRI. We extracted from a European multicentre prospectively gathered database the data of patients with a PI-RADS 5 lesion on pre-biopsy MRI, diagnosed using both systematic and targeted biopsies and subsequently treated by radical prostatectomy. The Kaplan-Meier model was used to assess the biochemical-free survival of the whole cohort and univariable and multivariable Cox models were set up to study factors associated with survival. Between 2013 and 2019, 539 consecutive patients with a PI-RADS 5 lesion on pre-biopsy MRI were treated by radical prostatectomy and included in the analysis. Follow-up data were available for 448 patients. Radical prostatectomy and lymph node dissection specimens showed non-organ confined disease in 297/539 (55%), (including 2 patients with a locally staged pT2 lesion and lymph node involvement (LNI)). With a median follow-up of 25months (12-39), the median biochemical recurrence-free survival was 54% at 2years (95% CI 45-61) and 28% at 5years (95% CI 18-39). Among the factors studied, MRI T stage [T3a vs T2 HR 3.57 (95%CI 1.78-7.16); T3b vs T2 HR 6.17 (95% CI 2.99-12.72)] and PSA density (HR 4.47 95% CI 1.55-12.89) were significantly associated with a higher risk of biochemical recurrence in multivariable analysis. Patients with a PI-RADS 5 lesion on pre-biopsy MRI have a high risk of early biochemical recurrence after radical prostatectomy. MRI T stage and PSA density can be used to improve patient selection and counselling.

Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis(DCA). Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), andEAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.

Clinical outcomes following biochemical recurrence among patients with Gleason score 9-10 prostate adenocarcinoma.

102 Background: Patients with Gleason score (GS) 9-10 prostate cancer (PCa) have a high risk of early biochemical recurrence (BCR). Salvage therapy options differ depending on the upfront management strategy. Patients who received upfront surgery (RP) may be curable with salvage external beam radiation therapy (EBRT). However those who underwent EBRT or EBRT with a brachytherapy boost (EBRT+BT) are less likely to receive local salvage therapy and are commonly treated with androgen deprivation therapy (ADT). In this study, we examine the risk of distant metastases (DM) and prostate-cancer specific mortality (PCSM) among patients with GS 9-10 PCa who had BCR following RP, EBRT, or EBRT+BT. Methods: 712 patients with GS 9-10 PCa treated between 2000-2013 at 12 institutions who had BCR were included (346 RP, 282 EBRT, 84 EBRT+BT). Time to DM and PCSM were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated using age, T-stage, PSA, and GS. Results: In patients who had a BCR, incidence rates of DM and PCSM after RP were 40% and 28%. Rates after EBRT were 60% and 46% and after EBRT+BT were 49% and 31%. Median times to DM and PCSM were 3.5 and 4.9 years after RP, 3.7 and 5.1 years after EBRT, and 3.3 and 6.8 years after EBRT+BT. The rates of local salvage RT and systemic salvage therapy among RP patients were 38% and 59%, respectively. Local and systemic salvage rates were 5% and 31% for EBRT patients and 5% and 28% for EBRT+BT patients. EBRT patients had a shorter time interval to DM compared with RP (HR 1.4, p = .02) and EBRT+BT (HR 1.9, p &lt; .01). EBRT patients also had a shorter time interval to PCSM compared with RP (HR 1.5, p = .02). Conclusions: Among patients with GS 9-10 PCa who experience BCR after definitive management, those treated with EBRT have a shorter time interval to DM and PCSM compared with RP and EBRT+BT. While this analysis is confounded by the differential thresholds for diagnosing a BCR after different modalities, it does suggest that outcomes following BCR after EBRT+BT and RP are similar. It also suggests that extreme dose escalation delays the onset of DM and PCSM even after BCR, when compared with conventionally-dosed EBRT alone.

Importance of Reporting the Gleason Score at the Positive Surgical Margin Site: Analysis of 4,082 Consecutive Radical Prostatectomy Cases

Since 2010 pathologists at our institution have routinely been documenting the Gleason score at the margin and length of the positive surgical margin after prostatectomy. In this study we evaluate how the Gleason score and positive surgical margin length correlate with the grade and adverse pathological characteristics of the final specimen, and whether the positive surgical margin Gleason score affects the risk of early biochemical recurrence. A total of 4,082 consecutive patients undergoing radical prostatectomy and pelvic lymph node dissection between 2010 and 2014 for localized prostate cancer were included in the study, of whom 405 had a Gleason score of 7 or greater of the primary nodule and a positive surgical margin with the length and Gleason score recorded at the margin. Concordance rates between the Gleason score at the margin and the final pathological specimen were compared. Logistic regression models were used to predict the risk of unfavorable pathology. Cox proportional hazards models controlling for Gleason score, preoperative prostate specific antigen, pathological stage and adjuvant radiation were used to predict biochemical recurrence, and Kaplan-Meier estimates of recurrence-free survival were calculated by Gleason score. Among patients with positive margins biochemical recurrence was identified in 22% (vs 5.6% without positive margins), metastases in 3% (vs 0.5%) and adjuvant radiation in 30% (vs 4.1%). Mean followup was 22 months (range 12 to 48). The Gleason score at the positive surgical margin was the same as the final pathology specimen in 44% of patients, and a lower Gleason score in 56% of patients. A shorter positive surgical margin was independently associated with a lower Gleason score at the margin (p=0.02). Kaplan-Meier estimates demonstrated improved freedom from biochemical recurrence among patients with a lower Gleason score at the margin. In multivariate Cox models having a lower grade margin was associated with a decreased risk of biochemical recurrence (HR 0.50, OR 0.25-0.97). A lower Gleason score at the positive surgical margin is independently associated with a shorter margin length and a decreased risk of early biochemical recurrence. Thus, the Gleason score at the margin should be documented.

422 Predictors of early failure after timely administered salvage radiotherapy for biochemical recurrence after radical prostatectomy

INTRODUCTION AND OBJECTIVES: The oncological safety of robot-assisted (RARP) and open radical prostatectomy (ORP) in patients with more aggressive disease is still debated. We aimed at comparing the biochemical recurrence (BCR) rates of RARP and ORP in patients with intermediate or high-risk prostate cancer (PCa). Additionally, since individuals experiencing early BCR are at increased risk of clinical progression and cancer-specific mortality, we assessed the impact of the surgical approach also on the risk of early BCR. METHODS: Overall, 2,181 patientswith intermediate or high-risk PCa (clinical stage T2b, biopsy Gleason score (GS) 7, and/or preoperative PSA 10ng/ml) treated at a single tertiary referral center between January 2006 and August 2013 were identified. No patient received neo-adjuvant or adjuvant therapies. BCR was defined as the detection of PSA 0.2ng/ml after surgery. Early BCR was defined as the occurrence of BCR within 2 years from surgery. Uniand multivariable (MVA) Cox regression analyses evaluated the association between the surgical approachand the risk of BCRandearly BCR, after accounting for confounders. Covariates consisted of clinical stage, biopsy GS, and preoperative PSA. Subsequently, we evaluated the impact of RARP on the risk of BCR and early BCR after accounting for pathological GS, pathological stage, surgicalmargin status (SM), and adjuvant treatments. RESULTS: Mean patient age was 64.9 years (median: 65). Overall, 1,522 (69.8%) and 659 (30.2%) patients were treated with ORP and RARP, respectively. Overall, the 5-year BCR-free survival rates were 79.8%. The 5-year BCR-free survival rates were 79.8% and 81.9% in patients treated with ORP and RARP, respectively (P1⁄40.7). At univariable Cox regression analysis, RARP was not associated with increased risk of BCR (Odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.72-1.58; P1⁄40.3) and early BCR (OR: 1.07; 95% CI: 0.78-2.06; P1⁄40.7). This was confirmed at MVA, where RARP was not associated with BCR and early BCR, after accounting both for preoperative (PSA, clinical stage, and biopsy GS) and postoperative (pathological stage, pathological GS, SM, lymph node invasion, and adjuvant treatments) confounders (all P>0.1). CONCLUSIONS: RARP and ORP have comparable 5-year BCR-free survival rates in patients with intermediateand high-risk PCa. Minimally invasive approach leads to comparable oncological outcomes in terms of BCR and early BCR. These results support the oncological safety of RARP in patients with intermediateand high-risk PCa.

PD27-07 IMPACT OF SURGICAL TECHNIQUE ON THE RISK OF BIOCHEMICAL RECURRENCE IN PATIENTS WITH INTERMEDIATE AND HIGH-RISK PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2014PD27-07 IMPACT OF SURGICAL TECHNIQUE ON THE RISK OF BIOCHEMICAL RECURRENCE IN PATIENTS WITH INTERMEDIATE AND HIGH-RISK PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY Giorgio Gandaglia, Marco Bianchi, Nazareno Suardi, Andrea Gallina, Umberto Capitanio, Andrea Salonia, Emanuele Zaffuto, Rocco Damiano, Francesco Cantiello, Pierre I. Karakiewicz, Maxine Sun, Shahrokh F. Shariat, Francesco Montorsi, and Alberto Briganti Giorgio GandagliaGiorgio Gandaglia More articles by this author , Marco BianchiMarco Bianchi More articles by this author , Nazareno SuardiNazareno Suardi More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , Umberto CapitanioUmberto Capitanio More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Rocco DamianoRocco Damiano More articles by this author , Francesco CantielloFrancesco Cantiello More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Maxine SunMaxine Sun More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2106AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The oncological safety of robot-assisted (RARP) and open radical prostatectomy (ORP) in patients with more aggressive disease is still debated. We aimed at comparing the biochemical recurrence (BCR) rates of RARP and ORP in patients with intermediate or high-risk prostate cancer (PCa). Additionally, since individuals experiencing early BCR are at increased risk of clinical progression and cancer-specific mortality, we assessed the impact of the surgical approach also on the risk of early BCR. METHODS Overall, 2,181 patients with intermediate or high-risk PCa (clinical stage ≥T2b, biopsy Gleason score (GS) ≥7, and/or preoperative PSA ≥10ng/ml) treated at a single tertiary referral center between January 2006 and August 2013 were identified. No patient received neo-adjuvant or adjuvant therapies. BCR was defined as the detection of PSA ≤0.2ng/ml after surgery. Early BCR was defined as the occurrence of BCR within 2 years from surgery. Uni- and multivariable (MVA) Cox regression analyses evaluated the association between the surgical approach and the risk of BCR and early BCR, after accounting for confounders. Covariates consisted of clinical stage, biopsy GS, and preoperative PSA. Subsequently, we evaluated the impact of RARP on the risk of BCR and early BCR after accounting for pathological GS, pathological stage, surgical margin status (SM), and adjuvant treatments. RESULTS Mean patient age was 64.9 years (median: 65). Overall, 1,522 (69.8%) and 659 (30.2%) patients were treated with ORP and RARP, respectively. Overall, the 5-year BCR-free survival rates were 79.8%. The 5-year BCR-free survival rates were 79.8% and 81.9% in patients treated with ORP and RARP, respectively (P=0.7). At univariable Cox regression analysis, RARP was not associated with increased risk of BCR (Odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.72-1.58; P=0.3) and early BCR (OR: 1.07; 95% CI: 0.78-2.06; P=0.7). This was confirmed at MVA, where RARP was not associated with BCR and early BCR, after accounting both for preoperative (PSA, clinical stage, and biopsy GS) and postoperative (pathological stage, pathological GS, SM, lymph node invasion, and adjuvant treatments) confounders (all P>0.1). CONCLUSIONS RARP and ORP have comparable 5-year BCR-free survival rates in patients with intermediate- and high-risk PCa. Minimally invasive approach leads to comparable oncological outcomes in terms of BCR and early BCR. These results support the oncological safety of RARP in patients with intermediate- and high-risk PCa. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e767 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Giorgio Gandaglia More articles by this author Marco Bianchi More articles by this author Nazareno Suardi More articles by this author Andrea Gallina More articles by this author Umberto Capitanio More articles by this author Andrea Salonia More articles by this author Emanuele Zaffuto More articles by this author Rocco Damiano More articles by this author Francesco Cantiello More articles by this author Pierre I. Karakiewicz More articles by this author Maxine Sun More articles by this author Shahrokh F. Shariat More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Percentage of high‐grade tumour volume does not meaningfully improve prediction of early biochemical recurrence after radical prostatectomy compared with Gleason score

To examine whether percentage of tumour volume (%TV) and percentage of high-grade tumour volume (%HGTV) help to better identify men at higher risk of early biochemical recurrence (BCR) after radical prostatectomy (RP) for non-metastatic high-risk prostate cancer, as early BCR after RP might be associated with higher risk of metastases and cancer-specific mortality. We examined the data of 595 men treated with RP for non-metastatic high-risk prostate cancer between 1992 and 2011 at two European tertiary care centres. Kaplan-Meier analyses were used to graphically depict 2-year BCR-free survival. Multivariable Cox regression models addressed early BCR. We tested whether addition of %TV and %HGTV to a multivariable Cox regression model helps to increase a model's predictive accuracy (PA) for prediction of early BCR. In all, 32 men (10%) with specimen-confined prostate cancer (pT2-pT3a, negative surgical margin, pN0) and 67 men (24%) with non-specimen-confined prostate cancer had early BCR. After stratification according to %HGTV (%HGTV threshold: ≤33.33 vs >33.33%), the 2-year BCR-free survival rates were respectively 93 vs 60% (log-rank P < 0.001). In multivariable Cox regression models %HGTV emerged as an independent predictor of early BCR (P < 0.001), whereas %TV did not (P > 0.05). However, adding %HGTV (regardless of its coding) to other covariates in multivariable Cox regression analysis did not increase the model's PA in a meaningful fashion compared with the use of the detailed Gleason grading system (6 vs 7a vs 7b vs 8 vs 9-10). In a large cohort of patients with high-risk prostate cancer, %HGTV and %TV did not improve prediction of early BCR after RP substantially, although %HGTV was an independent predictor of early BCR. Therefore, sophisticated TV/HGTV measurements do not seem to have additional benefit for early BCR prediction relative to the use of Gleason grading. However, these results need to be confirmed in larger, prospective studies.

Identification of miR-30d as a novel prognostic maker of prostate cancer

Prostate cancer (PCa) is the most common malignant carcinoma that develops in men in Western countries. MicroRNA (miRNA) have the potential to be used as biomarkers and therapeutic targets for the treatment of various cancers. We found significantly higher expression of miR-30d in 3 PCa cell lines (PC3, DU145 and LNCaP) compared with 2 normal prostate cell lines (RWPE-1 and PrSc) using miRNA microarrays and qPCR. Clinicopathological study revealed that miR-30d expression levels were significantly higher in cancer tissue samples than in the paired normal controls (P = 0.03). Furthermore, the miR-30d-high group had shorter time to biochemical recurrence (P = 0.026). MiR-30d overexpressed PCa cells promoted proliferation and invasion in vitro. Inoculation of miR-30d depleted PCa cells dramatically reduced tumor volumes in vivo. Using reporter gene assay, we identified miR-30d as a downregulator of SOCS1 expression by directly binding to 3'-UTR of SOCS1. MiR-30d regulated the expression of phospho-STAT3, MMP-2 and MMP-9 through the downregulation of SOCS1. The levels of SOCS1 mRNA and protein were significantly down-regulated in prostate cancer tissues. Consistently, miR-30d expression was inversely correlated with SOCS1 expression (P = 0.03). The miR-30d-high/SOCS1-low group was associated with an increased risk of early biochemical recurrence (P = 0.0057). Taken together, miR-30d appears to be a novel independent prognostic marker of PCa progression that allows clinicians to identify patients who need more intensive treatments.

Genetic predisposition to early recurrence in clinically localized prostate cancer

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Currently available nomograms to predict preoperative risk of early biochemical recurrence (EBCR) after radical prostatectomy are solely based on classic clinicopathological variables. Despite providing useful predictions, these models are not perfect. Indeed, most researchers agree that nomograms can be improved by incorporating novel biomarkers. In the last few years, several single nucleotide polymorphisms (SNPs) have been associated with prostate cancer, but little is known about their impact on disease recurrence. We have identified four SNPs associated with EBCR. The addition of SNPs to classic nomograms resulted in a significant improvement in terms of discrimination and calibration. The new nomogram, which combines clinicopathological and genetic variables, will help to improve prediction of prostate cancer recurrence. To evaluate genetic susceptibility to early biochemical recurrence (EBCR) after radical prostatectomy (RP), as a prognostic factor for early systemic dissemination. To build a preoperative nomogram to predict EBCR combining genetic and clinicopathological factors. We evaluated 670 patients from six University Hospitals who underwent RP for clinically localized prostate cancer (PCa), and were followed-up for at least 5 years or until biochemical recurrence. EBCR was defined as a level prostate-specific antigen >0.4 ng/mL within 1 year of RP; preoperative variables studied were: age, prostate-specific antigen, clinical stage, biopsy Gleason score, and the genotype of 83 PCa-related single nucleotide polymorphisms (SNPs). Univariate allele association tests and multivariate logistic regression were used to generate predictive models for EBCR, with clinicopathological factors and adding SNPs. We internally validated the models by bootstrapping and compared their accuracy using the area under the curve (AUC), net reclassification improvement, integrated discrimination improvement, calibration plots and Vickers' decision curves. Four common SNPs at KLK3, KLK2, SULT1A1 and BGLAP genes were independently associated with EBCR. A significant increase in AUC was observed when SNPs were added to the model: AUC (95% confidence interval) 0.728 (0.674-0.784) vs 0.763 (0.708-0.817). Net reclassification improvement showed a significant increase in probability for events of 60.7% and a decrease for non-events of 63.5%. Integrated discrimination improvement and decision curves confirmed the superiority of the new model. Four SNPs associated with EBCR significantly improved the accuracy of clinicopathological factors. We present a nomogram for preoperative prediction of EBCR after RP.

Serum methionine metabolites are risk factors for metastatic prostate cancer progression.

BackgroundClinical decision for primary treatment for prostate cancer is dictated by variables with insufficient specificity. Early detection of prostate cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics and adjuvant options prior to frank biochemical recurrence. This study compared markers in serum and urine of patients with rapidly recurrent prostate cancer to recurrence-free patients after radical prostatectomy. Based on previous identification of urinary sarcosine as a metastatic marker, we tested whether methionine metabolites in urine and serum could serve as pre-surgical markers for aggressive disease.Methodology/Principal FindingsUrine and serum samples (n = 54 and 58, respectively), collected at the time of prostatectomy were divided into subjects who developed biochemical recurrence within 2 years and those who remained recurrence-free after 5 years. Multiple methionine metabolites were measured in urine and serum by GC-MS. The role of serum metabolites and clinical variables (biopsy Gleason grade, clinical stage, serum prostate specific antigen [PSA]) on biochemical recurrence prediction were evaluated. Urinary sarcosine and cysteine levels were significantly higher (p = 0.03 and p = 0.007 respectively) in the recurrent group. However, in serum, concentrations of homocysteine (p = 0.003), cystathionine (p = 0.007) and cysteine (p<0.001) were more abundant in the recurrent population. The inclusion of serum cysteine to a model with PSA and biopsy Gleason grade improved prediction over the clinical variables alone (p<0.001).ConclusionsHigher serum homocysteine, cystathionine, and cysteine concentrations independently predicted risk of early biochemical recurrence and aggressiveness of disease in a nested case control study. The methionine metabolites further supplemented known clinical variables to provide superior sensitivity and specificity in multivariable prediction models for rapid biochemical recurrence following prostatectomy.