Clonal hematopoiesis in prostate cancer inferred from somatic tumor profiling.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17001-e17001
Author(s):  
Catherine Handy Marshall ◽  
Albert E Holler ◽  
Hua-Ling Tsai ◽  
Lukasz Gondek ◽  
Jun Luo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Somatic Tissue ◽  
Cox Proportional Hazards ◽  
Categorical Variables ◽  
Prognostic Impact ◽  
Liquid Biopsies ◽  
Tumor Biopsy ◽  
Clonal Hematopoiesis ◽  
Tumor Profiling

e17001 Background: Clonal hematopoiesis (CH) is a process associated with normal aging and may complicate the interpretation of liquid-biopsy genomic testing in oncology. Little is known about the prevalence of CH in prostate cancer as detected on somatic tumor profiling, or its association with clinical parameters and outcomes in prostate cancer. We sought to estimate the prevalence and clinical characteristics of patients with CH identified from tissue-based prostate cancer specimens. Methods: This was a retrospective study of men with prostate adenocarcinoma who underwent clinical somatic tissue-based next-generation sequencing using commercial platforms (n = 364). Patients with known hematologic malignancies (n = 7), and those with only liquid biopsies were excluded (n = 34), leaving 323 cases. Classical CH mutations were defined as those in DNMT3A, TET2 or ASXL1. Additional CH mutations included were defined as those in BCORL1, GNAS, SF3B1, JAK2 or PPM1D. Chi-squared tests were used to compare prevalence by categorical variables, Kruskal-Wallis tests to compare means across groups, and Cox proportional hazards were used for time-to-event analyses. Results: The prevalence of CH mutations in prostate cancer was 9% (30/323), and the prevalence of classical CH mutations was 7% (22/323)(Table). The most common mutations were in DNMT3A (n = 9), TET2 (n = 8) and ASXL1 (n = 5); other less common CH alterations were in GNAS and SF3B1 (n = 3 each), followed by CBL and JAK2 (n = 1 each). The most common site of tumor biopsy was the prostate (N = 266) followed by visceral (n = 19) and lymph node (N = 19) metastases. Men with any CH mutation were not significantly older at age of prostate cancer diagnosis (64 vs 62 years; p = 0.19) than those without; however, men with classical CH mutations were statistically older at diagnosis than those without (66 vs 62 years; p = 0.04). There was no difference in prevalence of CH mutations by Gleason sum (P = 0.67). Among men with localized disease at diagnosis, the median metastasis-free survival was 3.9 years in those with overall CH mutations and 6.6 years in those without CH mutations (HR [adjusted for age and Gleason] 1.3; 95% CI 0.7-2.3; p = 0.4). OS from the time of diagnosis to death was also numerically shorter in those with any CH mutation (median 9.7 years in those with and 14.2 years in those without CH mutations; HR 1.2, 95% CI 0.6-2.5; p = 0.6). Conclusions: CH can be detected in about 7-9% of prostate cancer patients from tissue-based tumor samples, is associated with older age, and may be linked to adverse oncological outcomes. The prognostic impact of CH in the context of specific systemic therapies (hormonal, chemotherapeutic) remains to be elucidated.[Table: see text]

The prognostic impact of a negative confirmatory biopsy in men on active surveillance for prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 76-76
Author(s):  
Keyan Salari ◽  
Dimitar V. Zlatev ◽  
David Kuppermann ◽  
Mark A. Preston ◽  
Douglas M. Dahl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Intraepithelial Neoplasia ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Atypical Small Acinar Proliferation ◽  
Diagnostic Biopsy

76 Background: Active surveillance (AS) is increasingly used in managing low-risk and favorable intermediate-risk prostate cancer. To mitigate the risk of unsampled higher risk disease, most institutional AS protocols call for a confirmatory prostate biopsy within 12-18 months following initial diagnostic biopsy. Here, we investigate whether the results of confirmatory biopsy impact the outcomes of men on AS. Methods: We retrospectively reviewed our institutional database of men enrolled in AS between 1997-2014 with a minimum follow-up of 6 months (n = 974). Biopsies with any prostate cancer were considered positive. Biopsies containing only benign prostatic tissue, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation (ASAP) were considered negative. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: At diagnosis, median age was 67 years (IQR 62-72) and median PSA was 5.1 ng/mL (IQR 3.9-6.8). The vast majority of patients had Gleason ≤6 (97%) and clinical stage T1 (92%) disease. With a median follow-up of 4.8 years, 702 (72%) patients underwent a confirmatory biopsy. 67% of confirmatory biopsies were positive for prostate cancer; 33% were negative (167 benign, 40 PIN, and 22 ASAP). Of the 702 patients, 33% progressed to treatment, with pathologic progression the most common reason (77%). Univariate predictors of progression to treatment included initial clinical stage ( P= 0.04), involvement of > 20% of any core on diagnostic biopsy ( P < 0.01), PSA density ≥0.15 ( P < 0.001), and confirmatory biopsy status ( P < 10-14). In multivariate analysis, a negative confirmatory biopsy remained the strongest predictor of progression to treatment (HR 0.12 [95%CI 0.06-0.24], P < 10-8). Confirmatory biopsy status was not associated with risk of adverse pathology on RP, metastasis-free survival, disease-specific survival, or overall survival. Conclusions: A negative confirmatory biopsy is associated with a significantly lower rate of progression to treatment among men on AS. This may serve as a useful tool for prognostication and help determine the need for further repeat biopsies for men on AS.

scholarly journals Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis—A Cross-Sectional Study

2021 ◽  
Vol 18 (8) ◽  
pp. 3983
Author(s):  
Ella Nissan ◽  
Abdulla Watad ◽  
Arnon D. Cohen ◽  
Kassem Sharif ◽  
Johnatan Nissan ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cross Sectional Study ◽  
Cox Proportional Hazards ◽  
Categorical Variables ◽  
Rank Test ◽  
Control Group ◽  
Multivariable Logistic Regression Analysis ◽  
Positive Trend ◽  
Continuous Variables ◽  
Cross Sectional

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case–control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student’s t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan–Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.

scholarly journals Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

2015 ◽  
Vol 33 (11) ◽  
pp. 1243-1251 ◽  
Author(s):  
Sean O'Farrell ◽  
Hans Garmo ◽  
Lars Holmberg ◽  
Jan Adolfsson ◽  
Pär Stattin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Gnrh Agonists ◽  
Cvd Risk ◽  
Comparison Cohort ◽  
Using Data

Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

Impact of KRAS mutational status on outcomes in patients with pancreatic cancer (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4142-4142
Author(s):  
Lucy Xiaolu Ma ◽  
Gun Ho Jang ◽  
Amy Zhang ◽  
Robert Edward Denroche ◽  
Anna Dodd ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Disease ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
First Line ◽  
Kras Mutations ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Translational Research Program ◽  
The Impact

4142 Background: KRAS mutations (m) (KRASm) are present in over 90% of pancreatic adenocarcinomas (PDAC) with a predominance of G12 substitutions. KRAS wildtype (WT) PDAC relies on alternate oncogenic drivers, and the prognostic impact of these remains unknown. We evaluated alterations in WT PDAC and explored the impact of specific KRASm and WT status on survival. Methods: WGS and RNAseq were performed on 570 patients (pts) ascertained through our translational research program from 2012-2021, of which 443 were included for overall survival (OS) analyses. This included 176 pts with resected and 267 pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657). The latter cohort underwent biopsies prior to treatment with first line gemcitabine-nab-paclitaxel or mFOLFIRINOX as per physician choice. The Kaplan-Meier and Cox proportional hazards methods were used to estimate OS. Results: KRAS WT PDAC (n = 52) represented 9% of pts, and these cases trended to be younger than pts with KRASm (median age 61 vs 65 years p = 0.1). In resected cases, the most common alterations in WT PDAC (n = 23) included GNASm (n = 6) and BRAFm/fusions (n = 5). In advanced WT PDAC (n = 27), alterations in BRAF (n = 11) and ERBB2/3/4 (n = 6) were most prevalent. Oncogenic fusions (NTRK, NRG1, BRAF/RAF, ROS1, others) were identified in 9 pts. The BRAF in-frame deletion p.486_491del represented the most common single variant in WT PDAC, with organoid profiling revealing sensitivity to both 3rd generation BRAF inhibitors and MEK inhibition. In resected PDAC, multivariable analyses documented higher stage (p = 0.043), lack of adjuvant chemotherapy (p < 0.001), and the KRAS G12D variant (p = 0.004) as poor prognostic variables. In advanced disease, neither WT PDAC nor KRAS specific alleles had an impact on prognosis (median OS WT = 8.5 mths, G12D = 8.2, G12V = 10.0, G12R = 12.0, others = 9.2, p = 0.73); the basal-like RNA subtype conferred inferior OS (p < 0.001). A targeted therapeutic approach following first line chemotherapy was undertaken in 10% of pts with advanced PDAC: MMRd (n = 1), homologous recombination deficiency (HRD) (n = 19), KRASG12C (n = 1), CDK4/6 amplification (n = 3), ERBB family alterations (n = 2), BRAF variants (n = 2). OS in this group was superior (14.7 vs 8.8 mths, p = 0.04), mainly driven by HRD-PDAC where KRASm were present in 89%. Conclusions: In our dataset, KRAS G12D is associated with inferior OS in resected PDAC, however KRAS mutational status was not prognostic in advanced disease. This suggests that improved OS in the WT PDAC population can only be achieved if there is accelerated access to targeted drugs for pts.

Fibroblast growth factor receptor alteration (FGFRa) status and progression outcomes of patients with advanced or metastatic urothelial cancer (mUC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4530-4530
Author(s):  
Sarah Fleming ◽  
Dina Gifkins ◽  
Waleed Shalaby ◽  
Jianjun Gao ◽  
Philip Rosenberg ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Prognostic Impact ◽  
Patient Records ◽  
Front Line ◽  
Convenience Sample ◽  
Adjusted Risk ◽  
Metastatic Urothelial Cancer

4530 Background: FGFRa appear in approximately 15% of cases of mUC. Data on whether FGFRa in mUC have a prognostic impact or predictive benefit for particular treatments have been limited by small sample sizes. The objective of this study was to evaluate the association between tumor FGFRa and clinical outcomes of patients with advanced UC or mUC regardless of therapy type and status. Methods: A convenience sample of oncologists and urologists across the United States provided patient level data on 400 patients with stage IIIb or IV UC via a standardized questionnaire over a 1-month period (August 17, 2020 – September 20, 2020). Study design enriched for FGFRa by requiring physicians to provide ≥1 FGFRa patient record. The questionnaire included physician characteristics, patient demographic information, FGFR status, therapy given, response, and clinical and radiographic measures of progression. Patient records were eligible for inclusion if they were identified and treated during July 1, 2017, to June 30, 2019. Cox proportional hazards models were used to estimate adjusted risk of disease progression by FGFR status. Results: A total of 104 physicians (58.7% medical oncologists, 31.7% hematologic oncologists, and 9.6% urologic oncologists) contributed 414 patient records Overall, 73.9% of the patients were male and the average age was 64.5 years (SD ±10.6). Median follow-up was 15 months. Of the 414 patients, 218 (52.7%) had FGFRa and 196 (47.3%) had FGFR wild-type ( FGFRwt) mUC . Of the 218 patients with FGFRa, 47.2% were treated with front-line chemo, 27.5% with a programmed death-ligand 1 inhibitor (PD-L1), 11.5% with chemo + PD-L1, and 13.8% with other treatments. Of the 196 FGFRwt patients, 63.2% were treated with front-line chemo, 21.9% with PD-L1, 12.2% with chemo + PD-L1, and 2.6% with other treatments. There was no difference in response or progression status for those receiving front-line chemo (HR, 1.15; 95% CI, 0.86-1.55). Among 97 patients (55 FGFRa and 42 FGFRwt) who received PD-L1 alone as front-line therapy, those who had FGFRa had an adjusted risk of progression 2 times higher than their FGFRwt counterparts (HR, 2.12; 95% CI, 1.13-4.00). Conclusions: Patients with FGFRa mUC progressed earlier than FGFRwt patients treated with front-line PDL-1 inhibitors; however, there was no difference in progression in patients treated with chemo based upon FGFR status. This real-world study using a survey design efficiently generated a relatively large FGFRa dataset, mitigating a core limitation of other studies assessing the patient population with FGFRa. Further work is warranted to validate these results and determine the optimal strategy for treating the patient with FGFRa mUC. Gene expression profiling of FGFRa mUC samples from clinical trials will help determine the potential impact of subtype or other features that may associate with benefit from therapy.

Abstract T MP48: Androgen Suppression in Patients with Prostate Cancer Increases Incidence of Combined Cardiovascular Outcomes

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Zuber S Ali ◽  
Danielle M Greere ◽  
Robyn L Shearer ◽  
Syed Ali Gardezi ◽  
Arshad Jahangir
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Age Groups ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Cardiovascular Outcomes ◽  
Elevated Risk ◽  
Disease Stage ◽  
Cox Proportional Hazards Models ◽  
Androgen Suppression

Introduction: Androgen suppression therapy for prostate cancer is controversial due to adverse fatal and non-fatal cardiovascular outcomes reported in some studies. However, effects of androgen suppression on stroke have not been fully assessed in the elderly. Methods: Patients diagnosed with prostate cancer during 2007-2013 in a large community-based healthcare system were identified from the Cancer Registry, electronic records, and billing codes. Those who underwent androgen suppression therapy with Gonadotropin-releasing hormone agonist (GnRH) were propensity-matched to patients treated without androgen suppression therapy by age at cancer diagnosis, race/ethnicity, disease stage and outcome, body mass index and use of surgery, radiation, and chemotherapy. Tests of independence and Cox proportional hazards models were used to examine effects of hormone therapy on acute myocardial infarction (AMI), stroke, and mortality outcomes. Models also adjusted for patient comorbidities. Results: A total of 1282 patients and 641 matched-pairs were identified, with mean diagnosis age of 69 yr and follow-up period of 3.05 yr. Effects of androgen suppression therapy on AMI (P=0.051) and stroke (P=0.062) were of marginal to non-significance, but adjusted-odds of death and combined AMI, stroke, and death were 1.61 times (P=0.002; odds ratio [OR] 95% CI: 1.19-2.18) and 1.70 times (P<0.001; OR 95% CI: 1.26-2.28) greater, respectively, for men with than without androgen suppression. An interaction of androgen suppression and age-group (<65 yr, 65-74 yr, >74 yr) was discovered for combined outcomes, suggesting increased probability of AMI, stroke, and/or death with age (8.6-20.0%; P=0.003) for patients without androgen suppression but elevated risk of outcomes across all age groups (18.3-22.4%; P=0.546) for men treated with androgen suppression therapy. Conclusion: Endogenous androgen suppression presents elevated risk of combined cardiovascular and death outcomes, especially for men <65 yr.

The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma

2020 ◽  
pp. 1-7
Author(s):  
Volkan İzol ◽  
Mutlu Deger ◽  
Ender Ozden ◽  
Deniz Bolat ◽  
Burak Argun ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Upper Urinary Tract ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Recurrence Time ◽  
Tumor Biopsy ◽  
Group 2 ◽  
Group 1

<b><i>Objective:</i></b> The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). <b><i>Materials and Methods:</i></b> Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. <b><i>Results:</i></b> After exclusion, a total of 194 patients were analyzed: Group 1 <i>n</i> = 95 (49.0%) and Group 2 <i>n</i> = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (<i>p</i> = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (<i>p</i><b> =</b>0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (<i>p</i><b></b>&#x3c; 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; <i>p</i> &#x3c; 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; <i>p</i> &#x3c; 0.001) was found to be an independent prognostic factor for IRFS. <b><i>Conclusion:</i></b> Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

Diagnostic and prognostic impact of circulating microRNA-208b and microRNA-499 in patients with acute coronary syndrome

2020 ◽  
Vol 14 (2) ◽  
pp. 87-95
Author(s):  
Wei Wang ◽  
Tai Li ◽  
Lei Gao ◽  
Yang Li ◽  
Ying Sun ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Major Adverse Cardiac Events ◽  
Circulating Microrna ◽  
Prognostic Impact ◽  
Cardiac Events ◽  
Primary Analysis ◽  
Coronary Syndrome ◽  
Adverse Cardiac Events

Aim: This study aimed to investigate the correlation between the expression of circulating miR-208b and miR-499 and acute coronary syndrome (ACS) patients. Materials & methods: A total of 160 consecutive patients with ACS and 48 healthy control subjects were enrolled for primary analysis. The ACS patients (n = 160) were followed up for 6 months for further analysis regarding major adverse cardiac events. Results: Area under the curve values of miR-208b and miR-499 for predicting ACS were 0.910 and 0.851 (p < 0.001, respectively). Cox proportional hazards regression analysis revealed that miR-208b but not miR-499 was an independent predictor of major adverse cardiac events. Conclusion: Circulating miR-208b and miR-499 could be considered as diagnostic or prognostic biomarkers for patients with ACS.

scholarly journals Prostate cancer-specific survival differences in patients treated by radical prostatectomy versus curative radiotherapy

2013 ◽  
Vol 7 (5-6) ◽  
pp. 299 ◽  
Author(s):  
Julie M. DeGroot ◽  
Michael D. Brundage ◽  
Miu Lam ◽  
Susan L. Rohland ◽  
Jeremy Heaton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Intermediate Risk ◽  
Cancer Specific Survival ◽  
Entire Study ◽  
Curative Radiotherapy ◽  
The Impact ◽  
Cause Specific Survival

Objective: We compared the cause-specific survival of patientswho received radiotherapy to those who received surgery for cureof their prostate cancer using a number of design and analytic stepsto mitigate confounding by indication.Methods: This was a case-cohort study of 2213 patients in theOntario Cancer Registry diagnosed between 1990 and 1998 whowere either treatment candidates or received curative radiotherapyor surgery. Cases included patients who died of prostate cancerwithin 10 years. The study population was restricted to those whowere candidates for either treatment (radiotherapy or surgery)based on disease severity (low and intermediate risk using theGenitourinary Radiation Oncologists of Canada risk groups). Themedian follow-up was 51 months. Cause-specific survival wasanalyzed using Cox-proportional hazards regression with casecohortvariance adjustment.Results from intent-to-treat analyseswere compared to results by treatment received.Results: Adjusted hazard ratios for risk of prostate cancer death forradiotherapy compared to surgery for the entire study populationwere 1.62 (95%CI 1.00-2.61) and 2.02 (1.19-3.43) analyzing byintent-to-treat and treatment received, respectively. Intent-to-treathazard ratios for the low- and intermediate-risk groups were 0.87(0.28-2.76) and 1.57 (0.95-2.61), respectively.Conclusion: Overall results were driven by the finding in the intermediate-risk group, which indicated that radiotherapy was not aseffective as surgery in this group. Confirmation was needed withspecial attention paid to risk stratification and the impact of morecontemporary delivery of these treatment options.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

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