scholarly journals Large Scale Genomic Instability as an Additive Prognostic Marker in Early Prostate Cancer

2009 ◽  
Vol 31 (4) ◽  
pp. 251-259
Author(s):  
Maria E. Pretorius ◽  
Håkon Wæhre ◽  
Vera M. Abeler ◽  
Ben Davidson ◽  
Ljiljana Vlatkovic ◽  
...  

Background: The clinical outcome for the individual prostate cancer patient is often difficult to predict, due to lack of reliable independent prognostic biomarkers. We tested DNA ploidy as a prognostic factor for clinical outcome in 186 patients treated with radical prostatectomy.Methods: DNA ploidy was measured using an automatic image cytometry system and correlated with preoperative PSA, age at surgery, Mostofi grade, surgical margins and Gleason score.Results: The mean follow up time after operation was 73.3 months (range 2–176 months). Of the 186 prostatectomies, 96 were identified as diploid, 61 as tetraploid and 29 as aneuploid. Twenty-three per cent, 36% and 62% of the diploid, tetraploid and aneuploid cases respectively, suffered from relapse during the observation time. DNA ploidy, Gleason score, Mostofi grading, surgical margins and preoperative PSA were all significant predictors of relapse in a univariate analysis. On multivariate analysis, only Gleason score and DNA ploidy proved to be independently predictors of disease recurrence. Furthermore, among the 68 cases identified with Gleason score 7, DNA ploidy was the only significant predictor of disease recurrence.Conclusion: Our data suggest that DNA ploidy should be included as an important additive prognostic factor for prostate cancer, especially for patients identified with Gleason score 7 tumours.

PROTEOMICS ◽  
2006 ◽  
Vol 6 (15) ◽  
pp. 4370-4380 ◽  
Author(s):  
Helena Lexander ◽  
Carina Palmberg ◽  
Ulf Hellman ◽  
Gert Auer ◽  
Magnus Hellström ◽  
...  

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e034612
Author(s):  
Athul John ◽  
Michael O'Callaghan ◽  
Rick Catterwell ◽  
Luke A Selth

IntroductionPositive surgical margins (PSM) in cancer patients are commonly associated with worse prognosis and a higher risk of secondary treatment. However, the relevance of this parameter in prostate cancer patients undergoing radical prostatectomy (RP) remains controversial, given the inconsistencies in its ability to predict biochemical recurrence (BCR) and oncological outcomes. Hence, further assessment of the utility of surgical margins for prostate cancer prognosis is required to predict these outcomes more accurately. Over the last decade, studies have used the Gleason score (GS) of positive margins to predict outcomes. Herein, the authors aim to conduct a systematic review investigating the role of GS of PSM after radical prostatectomy in predicting BCR and oncological outcomes.Methods and analysisWe will perform a search using MEDLINE, EMBASE, SCOPUS and COCHRANE databases. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will screen titles and abstracts to select articles appropriate for full-text review. Studies discussing GS of PSM after RP will be included. Given the change in reporting of GS, only articles from 2005 to 2019 will be included. The quality of the studies chosen will be assessed using the Newcastle Ottawa tool for non-randomised and Cochrane risk of bias for randomised control studies. We will adopt the grading of recommendations, assessment, development and evaluation framework to comment on quality of cumulative evidence. The primary outcome measure will be time to BCR. Secondary outcome measures include secondary treatment, disease-specific survival, disease progression-free and overall mortality at follow-up period. We aim to perform a meta-analysis if the level of heterogeneity is acceptable (I2<50%).Ethics and disseminationThe review does not require ethics approval as it is a review of published literature. The findings of the review will be submitted for peer-reviewed publications and presented at scientific meetings.PROSPERO registration numberCRD42019131800.


2013 ◽  
Vol 20 (11) ◽  
pp. 1097-1103 ◽  
Author(s):  
Riccardo Schiavina ◽  
Marco Borghesi ◽  
Michelangelo Fiorentino ◽  
Eugenio Brunocilla ◽  
Fabio Manferrari ◽  
...  

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 40-40
Author(s):  
R. D. Tendulkar ◽  
K. L. Stephans ◽  
C. A. Reddy ◽  
K. Martires ◽  
A. R. Patel ◽  
...  

40 Background: The percentage of positive cores (PPC) on biopsy for prostate cancer has been identified as a predictor of outcome following definitive local treatment. We aim to identify whether this observation holds true for a modern cohort of patients (pts) treated at Cleveland Clinic with permanent prostate brachytherapy (PB) or external beam radiation therapy (EBRT). Methods: We retrospectively reviewed pathology reports of pts treated with either PB or EBRT from our IRB-approved prospective prostate cancer registry. No pts underwent both PB and EBRT. The number of biopsy cores sampled, number of cores positive for prostate cancer, and maximum length of any core positive for prostate cancer were collected. Cox proportional hazards regression was used to analyze biochemical relapse free survival (bRFS) using the nadir + 2 ng/ml definition. Results: We identified 1253 PB and 879 EBRT pts with complete pathology and clinical information. Among PB pts, 46% were low risk, 40% intermediate risk, and 14% high risk, while 78% had <50% PPC, and 22% had >=50% PPC. The 5-year bRFS for PB was 92.0% for <50% PPC, vs. 83.1% for >=50% PPC (HR 2.1, p=0.0005). For PB pts, significant predictors of bRFS on univariate analysis included: PPC, clinical T stage, PSA, biopsy Gleason score, androgen deprivation, and frequency of PSA testing. On multivariate analysis, only PPC, biopsy Gleason score, and PSA frequency remained significant predictors following PB. Among EBRT pts, 11% were low risk, 36% intermediate risk, and 53% high risk, while 55% had <50% PPC, and 45% had >=50% PPC. The 5-year bRFS for EBRT was 85.6% for <50% PPC, vs. 77.1% for >=50% PPC (HR 1.8, p<0.0001). For EBRT pts, significant predictors of bRFS on univariate analysis included: PPC, clinical T stage, PSA, biopsy Gleason score, androgen deprivation, EBRT dose, and frequency of PSA testing. On multivariate analysis, only PPC, biopsy Gleason score, and PSA frequency remained significant predictors following EBRT. Conclusions: Following PB or EBRT, the percent of positive cores for prostate cancer was a significant predictor of bRFS on multivariate analysis, more so than conventional predictors such as T stage and PSA. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 75-75
Author(s):  
Victor Srougi ◽  
Rafael Sanchez-Salas ◽  
Fernando P. Secin ◽  
Igor Nunes-Silva ◽  
Mohammed Baghdadi ◽  
...  

75 Background: High-risk prostate cancer (PCa) is associated with greater risk of biochemical recurrence and cancer specific lethality. A multi-modal treatment is required for this group of patients, comprising surgery as part of it. However, the role of surgery as monotherapy is still under investigation. The purpose of this study is to analyze the influence of surgical margins on biochemical recurrence (BCR) among patients with high-risk prostate cancer (PCa) treated with robot assisted radical prostatectomy (RARP) since the start of our robotic program. Methods: We retrospectively analyzed our prospectively collected database of 5695 minimally invasive prostatectomies performed between 2000 and 2015. Clinical, pathological and oncological outcomes were evaluated in patients fulfilling Damico´s high risk characteristics. Primary endpoint was BCR, defined as post-operative PSA ≥ 0,2. Patients with neoadjuvant or adjuvant therapy were excluded. BCR was estimated with Kaplan-Meier curves. Cox proportional hazards regression was used to estimate variables associated with BCR. Results: We identified 199 high-risk PCa patients treated with RARP during the study period. Gleason score ≥ 8, PSA ≥ 20 and clinical stage ≥ T2c were present in 44%, 35% and 11% of the patients, respectively. The rate of positive surgical margins was 25%. With a median follow-up of 23 months (interquartile 12 – 34 months), 31% of the patients had BCR. Five-year BCR-free survival was 34,5%. Gleason score ≥ 8, PSA ≥ 20 and positive surgical margins were not predictors of BCR. A positive correlation of pathological stage ≥ T3 and BCR was found with (HR = 2.9; 95% CI = 1.2-6.9). Conclusions: The 5-years BCR-free survival was poor despite a low rate of positive surgical margins, when compared to historical series. We found that pathological stage ≥ T3 has a significant correlation with the BCR and that negative surgical margins do not assure good prognosis for high-risk patients.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Gustavo Jankilevich ◽  
Luciana Gennari ◽  
Matias Salazar ◽  
Claudio Graziano ◽  
Eduardo Saravia ◽  
...  

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 314-314
Author(s):  
Shinichi Sakamoto ◽  
Keisuke Ando ◽  
Nobushige Takeshita ◽  
Satoshi Yamamoto ◽  
Akira Komiya ◽  
...  

314 Background: We study the prognostic ability of androgen receptor amplification (AR amp) from cf DNA in Japanese castration-resistant prostate cancer (CRPC) patients. Methods: Multiple sets of serums were obtained from 38 castration-resistant prostate cancer patient at Chiba University hospital. Serum cfDNA was purified using a cobas cfDNA Sample Preparation Kit. AR copy number was measured using the QX100 Droplet Digital PCR System. Factors associated with progression-free survival (PFS) and Overall Survival (OS) were statistically studied. Results: The number of patients received Enzalutamide (Enza)/Abiraterone (Abi)/Docetaxel (Doc) were 33/25/11. Regarding PFS, the presence of AR amplification, Bone Scan Index (BSI), PSA was significant factors on univariate analysis. On multivariate analysis, AR amplification was an independent prognostic factor (HR. 8.9, p=0.003). Regarding OS, PSA and AR amp was significant factors. On multivariate analysis, AR amp (HR 4.2, p=0.028) was an independent prognostic factor. AR amp was related to the young age, high bone metastasis, high PSA, while no association was identified related the visceral metastasis. Overall, the presence of AR amp was negatively related to the initial ADT periods (r=-0.28). In contrary, among primary resistance cases (initial treatment periods <1 year), AR amp positively related to the treatment periods (r=0.31). Higher nadir testosterone (>15 ng/dL) was related to the higher AR amp (p=0.0169). AR amp was related to the treatment resistance in Enza (p=0.0216), while no relation was observed in Abi or Doc. Conclusions: AR amp significantly correlated with the poor prognosis. Higher serum testosterone level may predict the presence of AR amp in cf DNA. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.


2005 ◽  
Vol 3 (4) ◽  
pp. 0-0
Author(s):  
Daimantas Milonas ◽  
Dainius Burinskas ◽  
Stasys Auškalnis ◽  
Mindaugas Jievaltas

Daimantas Milonas, Dainius Burinskas, Stasys Auškalnis, Mindaugas JievaltasKauno medicinos universiteto Urologijos klinika,Eivenių g. 2, LT-50009 KaunasEl paštas: [email protected] Tikslas Nustatyti objektyvius veiksnius, kurie leistų prognozuoti ankstyvą biocheminį atkrytį po radikalios prostatektomijos. Ligoniai ir metodai Į tyrimą įtraukti 142 prostatos vėžiu sergantys ligoniai, kuriems buvo atliktos radikalios prostatektomijos. Ankstyvas biocheminis atkrytis konstatuotas, kai prostatos specifinio antigeno koncentracija, praėjus 3 mėn. po operacijos, buvo >0,2 ng/ml. Neoadjuvantinė terapija (hormonų ar spindulių) buvo pagrindinis atmetimo kriterijus. Vertinta prostatos specifinio antigeno koncentracija, vėžio diferenciacijos laipsnis iki ir po operacijos, vėžio stadija, prostatos chirurginio šalinimo išlaidos. Rezultatai Galutinei analizei panaudoti 94 ligonų duomenys. Vidutinis jų amžius buvo 66,6 metų, prostatos specifinis antigenas iki operacijos – 9,87 ng/ml, Gleason diferenciacijos laipsnis iki operacijos – 5,87, diferenciacijos laipsnis po operacijos – 6,38, teigiami rezekciniai kraštai rasti 36 (38%), ankstyvas biocheminis atkrytis – 13 (14%) pacientų. Atlikus logistinę regresijos analizę nustatyta, jog ankstyvą biocheminį atkrytį galima patikimai prognozuoti, kai Gleason pooperacinis vėžio diferenciacijos laipsnis didesnis nei 7 (p = 0,02, tikimybių santykis – 7,8) ir vėžio stadija T3b (p = 0,012, tikimybių santykis – 6,76). Išvados Remiantis ikioperaciniais objektyviais veiksniais negalima patikimai prognozuoti ankstyvo biocheminio atkryčio. Prostatos vėžio išplitimas į sėklines pūsleles (T3b stadija) ir Gleasono pooperacinis vėžio diferenciacijos laipsnis > 7 leidžia reikšmingai prognozuoti ankstyvą biocheminį atkryti, po radikalios prostatektomijos, tokiems ligoniams indikuojamas ankstyvas adjuvantinis gydymas, nelaukiant biocheminio atkryčio požymių. Reikšminiai žodžiai: prostatos vėžys, radikali prostatektomija, ankstyvas biocheminis atkrytis Can objective preoperative parameters predict early biochemical recurrence after radical prostatectomy? Daimantas Milonas, Dainius Burinskas, Stasys Auškalnis, Mindaugas JievaltasClinic of Urology, Kaunas University of Medicine,Eivenių str. 2, LT-50009 Kaunas, LithuaniaE-mail: [email protected] Objective To estimate objective parameters which can be useful for predicting early biochemical recurrence after radical prostatectomy due to prostate cancer. Patients and methods The study embraced 142 patients that underwent radical retropubic prostatectomy. Early biochemical failure was defined as a prostate-specific antigen level 3 months after radical prostatectomy > 0.2 ng/ml. Neoadjuvant treatment (hormonal therapy or radiation) was the mane exclusion criteria. Preoperative antigen concentration, Gleason score at the biopsy, patients’ age, postoperative Gleason score, stage and surgical margins were investigated as possible predictors of early biochemical recurrence. Results Final analysis was done using data on 94 patients. The mean patients’ age was 66.6 years and mean preoperative prostate specific antigen concentration 9.87 (range 0.44–98.4) ng/ml. The mean Gleason score preoperatively was 5.87 (range 2–8) and postoperatively 6.38 (range 4–9). Positive surgical margins were in 36 (38%) and early biochemical failure was detected in 13 (14%) cases. Logistic regression analysis shows that postoperative Gleason score >7 (p = 0.02, OR-7.8) and stage pT3b (p = 0.012, OR-6.76) are powerful parameters for predicting early biochemical recurrence. Conclusions Preoperative parameters cannot predict early biochemical recurrence. Postoperative parameters such as Gleason score >7 and stage pT3b are useful in the prediction of early biochemical recurrence. In such patients early adjuvant treatment is advisable. Keywords: prostate cancer, radical prostatectomy, early biochemical recurrence


Sign in / Sign up

Export Citation Format

Share Document