Biochemical Relapse In Patients Research Articles

The prognostic value of circulating miRNAs in patients with localized/locally advanced prostate cancer after radical prostatectomy and radiotherapy.

184 Background: The outcome after curative intended management of local prostate cancer (PC) is promising. However, there is still a risk of biochemical relapse (BR) after either radical prostatectomy (RP) or radiotherapy (RT). MicroRNAs (miRNAs) have showed encouraging results as alternative biomarkers in different settings of PCa. The aim of this study was to investigate the prognostic value of circulating miRNAs after management of local PCa. Methods: In total 107 newly diagnosed patients with local or locally advanced PCa were included in the study. The cohort was divided into an interventional group with 59 patients (RP (39 patients) or RT (20 patients)) and an observational group with 48 patients (active surveillance (AS)). Both baseline samples at time of diagnosis and follow-up samples six months after treatment were collected. The relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma using real-time polymerase chain reaction. Results: In the interventional cohort, the decrease in miRNA-125b after RT was significantly associated with a longer time to biochemical recurrence (BR) (HR= 0.17, p=0.03), and a higher level of miRNA-125b at baseline samples showed a tendency to higher risk for BR in the same population (HR= 2.82, p=0.09). On the other hand, lower levels of miRNA-221 at both baseline and follow-up samples tended to be associated with lower risk of BR in patients managed by RT (HR=0.14, p=0.07, and HR=0.13, p=0.07, respectively). None of these four miRNAs was associated with a significant risk of progression in patients managed by AS. Conclusions: Both baseline and the dynamics of miRNA-125b was informative as to the risk of BR in patients with PCa treated by RP. Validation in independent cohorts is called for.

The impact of positive vas deferens in the biochemical relapse in patients with stage T3b prostate cancer submitted to radical Prostatectomy

The study aimed to evaluate the influence of invasion of the vas deferens and seminal vesicles in patients undergoing radical prostatectomy for stage T3b tumor on biochemical recurrence.Methods: Retrospective analysis of 53 patients submitted to radical prostatectomy with anatomopathological stage T3b, at Hospital de Clínicas da Unicamp, between 1997 and 2014. After exclusion criteria were applied, statistical analysis of 32 participants separated into 2 groups, in which 20 patients (62.5 %) without involvement of the vas deferens (group 1) and 12 (37.5%) with invasion of the vas deferens (group 2). Biochemical recurrence was defined as an increase in prostate specific antigen (PSA) greater than or equal to 0.2 ng/ml after surgery. Results: Regarding the disease-free survival analysis, group 2 has a 3.05 times greater risk of having a biochemical recurrence compared to group 1 (HR 3.05, 95% CI 1.12-8.32, p=0.03), calculated by regression of Cox and Log Rank test. Conclusion: In conclusion, this study has identified an elevated risk of biochemical recurrence in patients with both ductus deferens and seminal vesicle invasion.

Prediction of prostate cancer recurrence after radiation therapy using multiparametric magnetic resonance imaging and spectroscopy: assessment of prognostic factors on pretreatment imaging.

To assess whether data from pre-therapeutic multiparametric magnetic resonance imaging (mpMRI) combined with three-dimensional magnetic resonance spectroscopy (3D MRS) provide prognostic factors of biochemical relapse in patients with localized prostate cancer treated by external radiotherapy or brachytherapy. In our single institution observational retrospective study we included a cohort of 230 patients treated by external radiotherapy or brachytherapy who had an initial mpMRI with 3D MRS from January 2008 to December 2015 for newly diagnosed localized prostatic cancer, proven histologically. Three trained radiologists recorded tumor characteristics, MRI T-stage and metabolic abnormalities from 3D MRS data. Univariate and multivariate Cox analyzes explored the relationship between clinical and imaging variables to highlight prognostic factors for recurrence, using biochemical relapse as the primary endpoint. mpMRI data analysis allowed to reclassify 21.7% of the patients in a MRI National Comprehensive Cancer Network (NCCN) group higher than their initial clinical T-stage, but also to detect a lesion in 78% of the patients considered as clinically T1c. After a median of follow-up of 8.7 years (IQR, 6.6-10.1) following cancer diagnosis, 36 (16%) patients developed a biochemical relapse. The multivariate Cox analysis demonstrated the existence of 3 independent factors for prediction of biochemical recurrence: extracapsular extension (ECE) (HR =3.33; 95% CI: 1.93-5.73; P<0.01), choline/citrate ratio in healthy tissue in the transition zone (TZ) (HR =2.96; 95% CI: 1.06-8.28; P=0.04) and the NCCN Magnetic Resonance Imaging classification (intermediate versus low-risk, HR =3.06; 95% CI: 1.13-8.30; P<0.01). Combination of mpMRI and 3DMRS could aid in the prognostic stratification of localized prostate cancer treated by radiotherapy or brachytherapy, by combining accurate evaluation of tumor extension, and quantification of prostate metabolism.

P37 - Incidence of biochemical relapse in patients after radical prostatectomy versus radical radiotherapy

P37 - Incidence of biochemical relapse in patients after radical prostatectomy versus radical radiotherapy

Serum hepatitis B virus RNA level is associated with biochemical relapse in patients with chronic hepatitis B infection who discontinue nucleos(t)ide analogue treatment.

Nucleos(t)ide analogue (NA) discontinuation may be attempted in carefully selected patients with chronic hepatitis B (CHB) infection. To investigate whether a novel serum marker of quantitative hepatitis B virus (HBV) RNA levels could predict biochemical relapse after NA discontinuation. We prospepctively followed non-cirrhotic Asian patients with CHB who stopped NA according to pre-specified stopping criteria. The primary endpoint was biochemical relapse (HBV DNA >2000IU/mL and alanine transaminase >2x upper limit of normal), which were also the re-treatment criteria. Biochemical relapse occurred in 50 patients (48.3% at year 6). Multivariable analysis showed that higher HBV RNA levels (HR 1.34; P<0.001) at the time of NA discontinuation were associated with increased biochemical relapse risk. The area under the curve of HBV RNA at the time of NA discontinuation for the incidence of biochemical relapse was 0.760 at 6years. Six years after treatment discontinuation, all patients with HBV RNA levels ≥20000copies/mL at the end of treatment developed a biochemical relapse compared with 23.8% of patients with HBV RNA levels<1000copies/mL (P<0.001). More patients with HBV RNA levels <1000 copies/mL at end of treatment achieved loss of hepatitis B surface antigen than patients with higher levels (30.9% vs 1.6%; P=0.027). The HBV RNA level at end of treatment predicted biochemical relapse after treatment discontinuation and may be used to guide decisions on treatment discontinuation.

The Role of Whole Body STIR MRI in Assessing First Biochemical Relapse in Patients with Myeloma

Background: Myeloma remains an incurable disease and most patients will relapse. The optimal timing of salvage initiation remains uncertain although there is a trend to treating early biochemical relapse. In the current COVID-19 pandemic, delaying therapy of asymptomatic relapsed patients is also desirable, but avoidance of renal failure and symptomatic bony disease is important. Whole body STIR MRI with diffusion weighted imaging (DWI) has the potential to diagnose bone involvement at a very early, pre-symptomatic stage, before cortical destruction occurs. It may be a useful tool to assess the ability to defer therapy in myeloma patients with asymptomatic biochemical relapse.Methods: We performed a retrospective audit of newly diagnosed patients with symptomatic myeloma, diagnosed between April 2012 and Oct 2019. We studied only patients in first relapse who had achieved PR or better to first-line therapy. Patients were typically monitored with monthly serum protein electrophoresis and free light chain assessments. The preferred imaging modality during the study period was whole body STIR MRI with DWI analysis and additional dedicated spinal sequences. Response and relapse criteria were as defined by the IMWG with the exception that regular urine BJP monitoring was not performed. Rapid biochemical relapse was defined as per Sonneveld (ASH Education Book 2017). The decision to initiate therapy for relapse was at the discretion of the treating hematologist.Results: 125 patients with newly diagnosed symptomatic myeloma who achieved PR or better to first line therapy were identified. Median age at diagnosis was 64yrs (range, 32 to 89yrs) and 72% were male. Immunoglobulin type was IgG (54%), IgA (23%), light chain (22%) and IgD (1%). ISS stage was I (19%), II (60%) and III (21%) and 21% were high risk as defined by the presence of t(4;14), t(14;16) or del17p by bone marrow FISH. Half received autologous stem cell transplantation with bortezomib-based therapy being the commonest induction for both transplant- and non-transplant-eligible populations. Amongst this group with responsive disease, haematological response was CR (38%), VGPR (29%) and PR (33%).75 (60%) of patients have relapsed at a median of 32 months. For patients in CR and VGPR, it took a median of 92 days from the first presence or increase in monoclonal immunoglobulin until IMWG defined relapse criteria were met. At the time of IMWG defined relapse, in terms of assessing need for therapy, the patients clinical status was defined as: rapid biochemical relapse (15%), relapse in a patient with high risk FISH (26%), relapse in a patient with renal failure at diagnosis (15%) and meeting CRAB criteria exclusive of MRI findings (7%), leaving 37% (n=27) in slow biochemical relapse without a definite indication for urgent therapy. MRI was performed as the bone imaging modality in 20 of these 27 slow biochemical relapse patients at a median of 42 days (range, -12 days to 210 days) after IMWG defined relapse: 10 demonstrated new focal bone lesions, 3 no lesions, 4 stable lesions and 3 improved bone lesions. Of these 10 patients with no new MRI detected bone disease, two were treated immediately at physician discretion.Thus, only 8 of 75 relapses were asymptomatic with a normal MRI, had no other indication for urgent therapy and were observed. For this group, the median time to treatment was 96 days (range, 34 to 576 days). Of these 5 had therapy initiated at physician discretion in the absence of clinical deterioration at a median of 78 days post biochemical relapse, one had treatment started 38 days after relapse due to renal deterioration and two were observed for 6 months and 1.4 years prior to the development of progressive focal bone lesions on MRI. None of the 10 patients with slow biochemical relapse and no new focal MRI bone lesions developed symptomatic bone disease within 6 months of that normal MRI.Conclusion: Whole body STIR MRI identifies new focal bone lesions in half of patients with slow biochemical relapse and no other treatment indication, justifying early therapy initiation at biochemical progression. In the setting of the COVID-19 pandemic, whole body STIR MRI with DWI may also be a useful tool to identify patients with slow biochemical relapse who are suitable for careful observation rather than salvage chemotherapy. Only a minority (11% in our study) of relapses, however, are potentially suitable for this approach.DisclosuresMollee:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees.

Factores de riesgo para recaída bioquímica en pacientes con cáncer de próstata tratados con crioablación en un Hospital de concentración de México

Objetivo: Determinar los factores de riesgo para recaída bioquímica (RB) en pacientes con cáncer de próstata (CaP) tratados con crioablación.&#x0D; Materiales y métodos: Estudio retrospectivo, transversal y analítico que incluyó 36 pacientes con CaP tratados con crioablación en el Hospital Central Militar, entre enero del 2012 y octubre del 2018. Se determinó la RB utilizando el criterio de Phoenix. Se realizó análisis bivariado y cálculo de Odds ratio (OR) con diferentes variables.&#x0D; Resultados: Media de seguimiento de 32.1 meses. APE nadir promedio de 2.07 ng/mL posterior a la crioablación, con una media para alcanzar este nivel de APE de 4.92 meses. Se identificaron 9 pacientes que desarrollaron RB. En el análisis de riesgo solo se identificó al APE nadir en su punto de corte &gt;0.8 ng/mL (OR 8.3, IC 95%, 1.40 – 49.06; p=0.01) como factor de riesgo para RB.&#x0D; Discusión: Primer estudio a nivel nacional que identifica al APE nadir como factor de riesgo para RB en pacientes con CaP tratados con crioablación.&#x0D; Conclusiones: En este estudio, el APE nadir es un factor de riesgo para RB en los pacientes con CaP tratados con crioablación, al demostrarse una elevación en el riesgo de 8.3 veces para desarrollar RB posterior al tratamiento.

Risk factors for biochemical relapse in patients with prostate cancer treated by cryoablation at a Mexican referral center

Objective: To determine the risk factors for biochemical relapse (BR) in patients with prostate cancer (PCa) treated by cryoablation.&#x0D; Materials and methods: A retrospective, cross-sectional, analytic study was conducted on 36 patients with PCa, treated by cryoablation at the Hospital Central Militar, within the time frame of January 2012 to October 2018. BR was determined utilizing the Phoenix criterion. A bivariate analysis was carried out and the odds ratio (OR) was calculated for different variables.&#x0D; Results: Mean follow-up duration was 32.1 months, mean PSA nadir was 2.07 ng/mL after cryoablation, with a mean of 4.92 months for reaching that PSA level. Nine patients developed BR. In the risk analysis, only the PSA nadir at its cutoff value &gt;0.8 ng/mL was identified as a risk factor for BR (OR 8.3, 95% CI, 1.40 – 49.06; p=0.01).&#x0D; Discussion: Ours is the first national study that identified the PSA nadir as a risk factor for BR in patients with PCa treated by cryoablation.&#x0D; Conclusions: In the present study, the PSA nadir was a risk factor for BR in patients with PCa treated by cryoablation, upon demonstrating an 8.3-fold higher risk for the development of BR after treatment.

Retrospective Cohort Analysis from a High-Volume Center of Prognostic Factors Affecting Biochemical Relapse in Patients with Encapsulated, Margin-Negative, Isolated Seminal Vesicle Invasion After Robot-Assisted Laparoscopic Prostatectomy: A Novel Study.

Purpose: Specimen pathology findings collectively impact the long-term outcomes of robot-assisted laparoscopic prostatectomy. Since seminal vesicle invasion (SVI) is an important independent predictor of biochemical recurrence (BCR), this study was designed to evaluate the influence of isolated SVI in the absence of capsular/margin invasion on BCR. Material and Methods: Pathology reports of 2009 robot-assisted laparoscopic prostatectomy specimens were analyzed retrospectively excluding capsular breach and/or margin-positive cases to include 1409 patients in the study. Factors predicting SVI and BCR in this select group of patients were assessed and statistically analyzed. Survival analysis for PSA (prostate-specific antigen) failure probability and binomial regressions for variable predictability were performed. Results: The African American race was associated with SVI (p < 0.05). PSA had a directly proportional correlation with the occurrence of SVI and BCR. SVI was found to be an independent predictor of BCR, leading to higher odds of BCR at 5 years (odds ratio [OR] 8.2, 95% confidence interval [CI] 4.5-14.6, p < 0.0001). When the seminal vesicle was invaded, the specimen Gleason grade group (SGGG; OR 1.9, 95% CI 1.02-3.7, p = 0.04), PSA (OR 1.2, 95% CI 1.01-1.4, p = 0.03), and BMI (body mass index) (OR 1.2, 95% CI 1.04-1.5, p = 0.01) predicted BCR. Seminal vesicle involvement was not found in SGGG 1. Risk stratification of significant predictors of BCR with isolated SVI identified a subgroup with BMI ≤27.9 kg/m2, PSA ≤8.6 ng/mL, and SGGG 2, which had a significantly better prognosis (p = 0.029, log-rank test). Conclusions: Seminal vesicles are infrequently involved with SGGG 1. Select groups of patients with isolated SVI who have low-grade disease with relatively lower PSA and BMI do not have an aggressive biological behavior and are unlikely to have a BCR, thereby circumventing unnecessary adjuvant therapy with its attendant side effects. The BMI significantly predicted PSA failures and should be considered as an additional risk assessment tool.

Factors Related to Biochemical Relapse in Patients Undergoing Radical Prostatectomy with Lymphadenectomy.

Objectives - Analyze the prevalence of biochemical recurrence (BCR) in patients submitted to radical prostatectomy with lymphadenectomy (RP-LD) the most prevalent clinical and pathological staging in the BCR and to correlate the sum of the Gleason score (GS) in the surgical specimen in patients who presented BCR. Method - Analysis of 100 patients diagnosed with prostate adenocarcinoma who performed RP-LD between 2013 to 2017. All subjects underwent transrectal prostate biopsy due to PSA or rectal examination and RP-LD. The lymphadenectomy considered in the study was the iliac-obturator, and the surgical pieces were analyzed to determine the pathological staging and its descriptors. All patients who had two or more PSA measurements &gt;0.2 ng/ml and who had undergone RP-LD were considered postoperative. Results -About 22% of the patients submitted to RP-LD presented BCR. Patients with BCR had a 59-76 age range, mean age of 66.27 years, and median age of 63.50 years. The most prevalent preoperative PSA in patients with BCR was between 10-20 ng/ml (40.90%) and the most prevalent clinical stage was cT2 (59.10%). Regarding the Gleason score, the BCR patients had the most prevalent 6 (36.37%) score in the biopsy and score 7 (4 + 3) (36.37%) in the surgical specimen. All patients (100%) with BCR presented perineural invasion, with pT3 staging (81.81%) and pN0 (77.28%) being the most prevalent in patients with BCR. Patients with BCR presented a correlation (p&lt;0.05) between the increase in the sum of pathological GS and the increase in pTN staging. Conclusion - All these variables were important in the determination of BCR in patients submitted to RP-LD, thus demonstrating the importance of this information in the analysis of the prognosis and in the follow-up of these patients.

Fit Patient with Nonmetastatic Castration-resistant Prostate Cancer, Lower Urinary Tract Symptoms, and Severe Recurrent Haematuria

For biochemical relapse in patients with nonmetastatic castration-resistant prostate cancer previously treated with androgen deprivation alone, external beam radiotherapy to the primary tumour and the pelvic lymph nodes is preferable to radical prostatectomy with lymphadenectomy.

Loss of AZGP1 as a Superior Predictor of Relapse in Margin-Positive Localized Prostate Cancer.

Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs. Our study aimed to determine whether the biomarkers AZGP1 expression and Gleason grade at the site of a PSM are significant independent markers of biochemical and clinical relapse (CR) when modeled together and whether one of these biomarkers may be superior in its capacity to predict outcome. A cohort of 275 consecutive patients with margin-positive localized PC following surgery were assessed for Gleason grade and AZGP1 expression at the PSM. BR-free survival was the primary end-point, while CR-free survival and PC-specific death were secondary endpoints. Kaplan-Meier Analysis and Cox Proportional Hazards Modeling were performed. Absent AZGP1 expression was significantly associated with increased risk of BR (P = 0.001) and PC-specific death (P = 0.02). Gleason grade ≥4 at PSM was associated with BR (P = 0.02), CR (P = 0.003), and PC-specific death (P = 0.004). On multivariable analysis, absent AZGP1 expression remained an independent predictor of BR (HR 2.4, 95%CI 1.5-3.9, P < 0.001) when modeled with Gleason grade at margin (HR 1.3, 95%CI 0.9-1.9, P = 0.16), preoperative PSA (P = 0.002), seminal vesicle involvement (P = 0.002), extraprostatic extension (P = 0.001), Gleason score (P = 0.01), adjuvant treatment (P = 0.75), linear length of the involved margin (P = 0.001) and margin number (P = 0.09). Absent AZGP1 expression is an independent predictor of BR in margin-positive localized PC and is associated with increased PC-specific mortality in a Phase II study. Absent AZGP1 expression was superior to Gleason grade at PSM in predicting relapse and should be incorporated into subsequent clinical trials of post-operative radiotherapy in men with margin-positive PC. Prostate 76:1491-1500, 2016. © 2016 Wiley Periodicals, Inc.

732 Pathological T2b and T2c subgrouping may not be needed for predicting biochemical relapse in patients treated by radical prostatectomy

732 Pathological T2b and T2c subgrouping may not be needed for predicting biochemical relapse in patients treated by radical prostatectomy

Dominant Intraprostatic Lesion Size Is Correlated With Rate of Biochemical Relapse in Patients With High- and Intermediate-Risk Prostate Cancer Treated With Intensity Modulated Radiation Therapy

Dominant Intraprostatic Lesion Size Is Correlated With Rate of Biochemical Relapse in Patients With High- and Intermediate-Risk Prostate Cancer Treated With Intensity Modulated Radiation Therapy

Identification of prostate cancer risk categories according to surgical margins status, pathological stage and Gleason score

One-third of patients with positive surgical margins after radical prostatectomy develop recurrent disease. The distinction between pT2 with positive margins and pT3a can be difficult. Aim of the present study was to assess the impact of positive surgical margins on biochemical relapse after radical prostatectomy, adjusted for pathological stage and Gleason score. We retrospectively evaluated 837 consecutive patients who underwent radical prostatectomy for organ-confined or locally-advanced prostate cancer. Exclusion criteria were: presence of node or distant metastases, neo-adjuvant or adjuvant therapy, and unavailability of full data regarding pathological stage and margin status. A single dedicated genitourinary pathologist evaluated all the specimens. The Kaplan-Meier method and univariable and multivariable Cox regressions were applied for survival analyses. The median follow up was 54.0 ± 35.0 months. Margin status, prostate-specific antigen and Gleason score significantly predicted biochemical relapse in the pT2 group at multivariable analysis, whereas only pathological stage and pathological Gleason score were significant predictors of recurrence in pT3a patients. There were no significant differences in biochemical disease-free survival among pT2 with positive margins patients and pT3a patients (with or without positive surgical margins). Pathological Gleason score was the only significant predictor of biochemical relapse in patients with negative and positive margins, regardless of the pathological stage. pT2 patients with positive surgical margins and pT3a (with or without positive margins) seem to have similar biochemical disease-free survival. Positive margins and pathological stage might be insufficient clinical predictors. Gleason score remains the most reliable prognostic factor.

763 PROGNOSTIC IMPACT OF ZOLEDRONIC ACID ON BIOCHEMICAL RELAPSE IN TREATMENT-NAÏVE PATIENTS WITH BONE-METASTATIC PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2012763 PROGNOSTIC IMPACT OF ZOLEDRONIC ACID ON BIOCHEMICAL RELAPSE IN TREATMENT-NAÏVE PATIENTS WITH BONE-METASTATIC PROSTATE CANCER Hideyasu Matsuyama, Masahiro Nozawa, Takeshi Inagaki, Kazuhiro Nagao, Isao Hara, and Hirotsugu Uemura Hideyasu MatsuyamaHideyasu Matsuyama Ube, Japan More articles by this author , Masahiro NozawaMasahiro Nozawa Osaka-Sayama, Japan More articles by this author , Takeshi InagakiTakeshi Inagaki Wakayama, Japan More articles by this author , Kazuhiro NagaoKazuhiro Nagao Ube, Japan More articles by this author , Isao HaraIsao Hara Wakayama, Japan More articles by this author , and Hirotsugu UemuraHirotsugu Uemura Osaka-Sayama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.850AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Zoledronic acid has been reported to have an anti-proliferative activity. Recent studies suggest that bone metabolism markers predict patient outcome in prostate cancer. Aims of this study were if bone metabolism markers may predict clinical outcome in patients with metastatic prostate cancer who were treated both with zoledronic acid and with androgen deprivation therapy (ADT), and if zoledronic acid has oncological benefit in those patients. METHODS A multi-institutional prospective phase II study was conducted for 54 treatment-naïve patients with bone-metastatic prostate cancer who were treated with ADT in combination with zoledronic acid (ADT-Z group). Median age, baseline PSA of the patients were 72, and 249ng/ml, respectively. Zoledronic acid was intravenously given 4 mg every 4 weeks concurrently with ADT comprising of bicalutamide (80mg po) and goserelin acetate (10.8mg sc every 3 months), and followed with a median follow-up of 24.6 months. Bone-specific alkaline phosphatase (BAP), cross-linked C-terminal telopeptides of type I collagen (I-CTP), urine levels of cross-linked N-terminal telopeptides of type I collagen (NTx) were measured bone metabolism markers before treatment followed by every 3 months thereafter, and were compared with biochemical relapse (BCR). BCR of ADT-Z group was compared with that of historical control consisting of 180 patients with metastatic prostate cancer who were treated with ADT alone (ADT group). RESULTS Baseline NTx (>100), baseline PSA (>225), EOD (>2) were significantly linked with shorter time to BCR. Baseline NTx (>100) was an independent predictor for BCR in multivariate analysis (p=0.02). Time to BCR was significantly longer in ADT-Z group than that in ADT group (p<0.0001, median TTP: not reached in ADT-Z vs. 15.4 months in ADT). CONCLUSIONS Combination therapy of zoledronic acid with ADT may prolong time to BCR in patients with treatment-naïve metastatic prostate cancer, and baseline NTx may be a useful predictor in those patients. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e312 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hideyasu Matsuyama Ube, Japan More articles by this author Masahiro Nozawa Osaka-Sayama, Japan More articles by this author Takeshi Inagaki Wakayama, Japan More articles by this author Kazuhiro Nagao Ube, Japan More articles by this author Isao Hara Wakayama, Japan More articles by this author Hirotsugu Uemura Osaka-Sayama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

781 Interval of freedom from biochemical relapse in patients with recurrent prostate cancer after salvage extended lymph node dissection. Experience at the Kiel University Hospital

781 Interval of freedom from biochemical relapse in patients with recurrent prostate cancer after salvage extended lymph node dissection. Experience at the Kiel University Hospital

Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

The clinical features of prostate cancer do not provide an accurate determination of patients undergoing biochemical relapse and are therefore not suitable as indicators of prognosis for recurrence. New molecular markers are needed for proper pre-treatment risk stratification of patients. Our aim was to assess the value of altered expression of syndecan-1 and -2 as a marker for predicting biochemical relapse in patients with clinically localized prostate cancer treated by radical prostatectomy. The expression of syndecan-1 and -2 was examined by immunohistochemical staining in a series of 60 paraffin-embedded tissue samples from patients with localized prostate cancer. Ten specimens from patients with benign prostatic hyperplasia were used as non-malignant controls. Semiquantitative analysis was performed to evaluate the staining patterns. To investigate the prognostic value, Kaplan-Meier survival curves were performed and compared by a log-rank test. In benign samples, syndecan-1 was expressed in basal and secretory epithelial cells with basolateral membrane localisation, whereas syndecan-2 was expressed preferentially in basal cells. In prostate cancer samples, the expression patterns of both syndecans shifted to granular-cytoplasmic localisation. Survival analysis showed a significant difference (P < 0.05) between normal and altered expression of syndecan-1 and -2 in free prostate-specific antigen recurrence survival curves. These data suggest that the expression of syndecan-1 and -2 can be used as a prognostic marker for patients with clinically localized prostate cancer, improving the prostate-specific antigen recurrence risk stratification.

Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase &lt;1.5 ng/ml?

The aim of this study was to evaluate the potential usefulness of whole-body (11)C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 ± 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series (11)C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. (11)C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of (11)C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive (11)C-choline PET/CT scan. Overall, (11)C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, (11)C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS-guided biopsy in 7 patients with local recurrence, (b) surgery and lymphadenectomy in 3 patients, (c) other targeted imaging procedures (MR or bone scan) in 5 patients and (d) clinical FU lasting a minimum of 12 months and including also a contrast-enhanced CT (CECT), an MR, a bone scan and a repeated (11)C-choline PET/CT in 14 patients. Age, time to biochemical relapse (TTR), initial T staging, Gleason score and trigger PSA were not statistically significant in predicting a positive (11)C-choline PET/CT scan both at univariate and multivariate analysis. Instead, PSA kinetics (PSAdt and PSAvel), N status and anti-androgenic therapy at the time of PET scan were statistically significant predictive factors at univariate analysis. Of note, only PSAdt and initial N status were found to be significant and independent predictive factors at multivariate analysis. The mean PSAdt in PET-positive patients was 4.34 months (SD 2.82) while in PET-negative patients it was 13.30 months (SD 9.75) (p = 0.0001). The optimal threshold for PSAdt established by receiver-operating characteristic (ROC) analysis was 7.25 months (AUC 0.85; 95% confidence interval 0.77-0.91) providing 93% sensitivity, 74% specificity, 60% positive predictive value and 96% negative predictive value. In our study, (11)C-choline PET/CT was able to detect recurrent disease in 28% of the patients with mild biochemical relapse characterized by very low trigger PSA levels (PSA <1.5 ng/ml). Very interestingly (11)C-choline PET/CT detected distant unexpected metastases in 21% of the patients. At multivariate statistical analysis only PSAdt and node status were shown to be significant and independent predictive factors for positive (11)C-choline PET/CT. Therefore, (11)C-choline could be suggested to be performed early during initial biochemical relapse in patients presenting with fast PSA kinetics. The early detection of the site of recurrence could lead to a prompt instauration of the most appropriate treatment, i.e. local surgery or radiation treatment vs systemic treatment. In this view, one of the main advantages should be the avoidance of unnecessary local radiotherapy in those patients showing distant metastasis at (11)C-choline PET/CT.

Predicting Post–External Beam Radiation Therapy PSA Relapse of Prostate Cancer Using Pretreatment MRI

To investigate whether pretreatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer treated with external beam radiation therapy (EBRT). Between January 2000 and January 2002, 224 patients (median age, 69 years; age range, 45-82 years) with biopsy-proven prostate cancer underwent endorectal MRI before high-dose (≥81Gy) EBRT. The value of multiple clinical and MRI variables in predicting prostate-specific antigen (PSA) relapse at 5 years was determined by use of univariate and multivariate stepwise Cox regression. Clinical variables included pretreatment PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and radiation dose. Magnetic resonance imaging variables, derived from retrospective consensus readings by two radiologists, were used to measure intraprostatic and extraprostatic tumor burden. After a median follow-up of 67 months, PSA relapse developed in 37 patients (16.5%). The significant predictors of PSA relapse on univariate analysis were pretreatment PSA, clinical T stage, and multiple MRI variables, including MRI TN stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors on multivariate analysis (p < 0.05 for both). Extracapsular extension status was associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pretreatment PSA being significant independent predictors of this endpoint.