Serum insulin to predict time to castration-resistant progression and overall survival in metastatic androgen-dependent prostate cancer (mADPCa).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16038-e16038
Author(s):  
Farshid Dayyani ◽  
Graciela M. Nogueras-Gonzalez ◽  
Rebecca Slack ◽  
Randall E. Millikan ◽  
Amado J. Zurita ◽  
...  

e16038 Background: Duration of response to androgen-deprivation therapy (ADT) is highly variable in patients with mADPC and prognostic markers are needed. Insulin resistance and hyperinsulinemia may contribute to prostate cancer progression. We hypothesized that pretreatment serum insulin levels would predict time to castration-resistant progression (PFS) and overall survival (OS). Methods: Sera from men treated on a randomized phase 3 trial of first line ADT vs. ADT plus chemotherapy were retrospectively analyzed using a multiplex ELISA for cytokines and angiogenic factors (CAFs). Univariate and multivariate Cox proportional hazards regression models were used to identify associations between CAFs and PFS/OS. Results: 66 pts were evaluable, 86% Caucasian, median age 72 yrs, median PSA 31.5ng/mL, 77% Gleason score of ≥8, and 53% high volume metastatic disease (HVM). Thirty-five pts received ADT; 31 pts received ADT+chemo. In univariate analysis, higher pretreatment insulin and C-peptide were positively correlated with PFS, whereas higher hepatocyte-growth factor (HGF), osteopontin (OPN) and HVM were negatively correlated with PFS. In multivariate analysis, only higher insulin was associated with longer PFS (HR=0.72, 95%CI 1.32 -0.87; p<0.001), whereas higher HGF and OPN were associated with reduced PFS (HR=1.82, 95%CI 0.59-2.83, p<0.01 and HR=1.81, 95%CI 1.18-2.47, p<0.001, respectively). Higher Insulin and Program Death 1 (PD1) were associated with longer OS on multivariate analysis (HR=0.78 p<0.02 and HR=0.55 p<0.02, respectively), whereas HVM and higher OPN were associated with reduced OS (HR=2.28 p<0.01 and HR=1.60 p<0.02). Using low insulin, high HGF and high OPN as 3 independent risk factors (RF), 3 distinct risk groups could predict PFS: good (zero RF), intermediate (1 or 2 RF) and poor risk (3 RF), with median PFS of 6.90, 1.97, and 0.86 years, respectively (p<0.001). Conclusions: Higher pretreatment insulin was associated with prolonged PFS and OS in men with mADPC treated with ADT. Our data suggest that insulin levels are a biomarker for sensitivity to ADT and highlight the complex interactions between metabolism and PCa progression.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  

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]


2020 ◽  
Author(s):  
Shotaro Nakanishi ◽  
Masato Goya ◽  
Mitsuyoshi Tamaki ◽  
Takuma Oshiro ◽  
Seiichi Saito

Abstract Background The effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) patients has not been well investigated. Here, we evaluated the effect of factors that lead to castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC. Methods Medical records of 71 consecutive primary mHSPC patients treated with ADT were analyzed. Factors predicting the time to CRPC and OS in these patients were evaluated at 3 months after ADT induction. Results The median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis using Cox proportional hazards regression, a Gleason score of 8 or more (p = 0.004), extent of disease value (EOD) of 2 or more (p = 0.004), and a PSA level of 1% or more of the pretreatment levels after 3 months of ADT (p = 0.017) were independent predictors of shorter time to CRPC. For OS, a PSA level of 1% or more after 3 months of ADT was the independent predictor (p = 0.004). Conclusion % PSA was an important factor that correlated with poor prognosis at 3 months after ADT induction.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 168-168
Author(s):  
Jasmine Jiemei Wang ◽  
Pai-Chi Teng ◽  
Yu Jen Jan ◽  
Jie-Fu Chen ◽  
Galen Cook-Wiens ◽  
...  

168 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PC). Previously, a subgroup of PC CTCs, with particularly small nuclei (<8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We proposed vsnCTCs as a putative biomarker of a lethal subtype in metastatic castration resistant PC (mCRPC). Methods: In this study, 76 patients with mCRPC were recruited for overall survival (OS) analysis. Of the 76 patients, 47 had available pre-treatment blood specimens prior to the initiation of androgen receptor signaling inhibitor (ARSI, e.g. abiraterone and enzalutamide) or taxane therapy. Using the NanoVelcro CTC Assay, CTCs were captured and subjected to immunofluorescence staining. CTCs were identified as DAPI+/CK+/CD45- with a round or oval nucleus. Additionally, CTC nuclear size was measured and defined as the square root of the product of the long axis and the short axis. Kaplan-Meier analysis and Cox proportional hazards model were conducted. Results: Patients with vsnCTC (i.e., vsnCTC+) had a significantly shortened OS compared with patients without vsnCTC (i.e., vsnCTC-). The median OS was 34 (vsnCTC+, n=49) vs. 149 (vsnCTC-, n=27) weeks (log-rank HR=2.6 with 95% CI 1.5 to 4.5, p=0.0006). Progression free survival (PFS) analysis was performed for the 47 patients with pre-treatment blood samples. The median PFS was 14 (vsnCTC+, n=29) vs. 26 (vsnCTC-, n=18) weeks (log-rank HR=2.2 with 95% CI 1.2 to 3.9, p=0.0069). We also found that the hazard ratio of overall survival increased significantly as the CTC nuclear size decreased using the p spline plot. Conclusions: Our study showed that nuclear size reduction has importance in CTCs in a fashion similar to its utility in tissue. This study points toward the importance of the vsnCTC in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for morality. We posit that the vsnCTC represents a new hallmark of an aggressive subtype of mCRPC. This has potential importance in optimizing therapeutic choices.


2021 ◽  
Vol 42 (2) ◽  
pp. 131-137
Author(s):  
Isaris Chaokhamin ◽  
◽  
Worapat Attawettayanon ◽  
Virote Chalieopanyarwong ◽  
Monthira Tanthanuch ◽  
...  

Objective: Many treatment options of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy have proved efficacious in clinical trials but, to date, knowledge regarding oncological outcomes is limited. Materials and Methods: We assessed the oncological outcome of 4 drugs (abi- raterone acetate, cabazetaxel, enzalutamide and ketoconazole) in a normal clinical setting in a university-based hospital. Our cohort consisted of 69 patients with post-docetaxel mCRPC. The primary endpoint was overall survival (OS). The secondary endpoint was predicted factor associated overall survival with all sec- ond-line mCRPC treatment outcomes according to the Cox proportional hazards regression model. Results: This cohort consisted of 69 patients with progressive mCRPC after docetaxel chemotherapy. Median overall survival following treatment with abiraterone acetate and ketoconazole was 25.92 and 9.59 months respectively (p < 0.05). Overall survival rates at 1-year following abiraterone acetate, cabazetaxel, enzalutamide and ketoconazole therapy were 76.3%, 83.3%, 100% and 41.9%, respectively. Multivariable analysis found that abiraterone acetate, cabazitaxel and enzalutamide significantly improved survival in comparison to ketoconazole (p < 0.001). Conclusion: Analysis of overall survival following second-line treatment of mCRPC post docetaxel in our study statistically significantly confirmed that abiraterone acetate, cabazitaxel and enzalutamide improve overall survival in comparison to ketoconazole. The study also found that enzalutamide treatment resulted in better outcomes in comparison to the other drugs.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 240-240
Author(s):  
Sina Vatandoust ◽  
Ganessan Kichenadasse ◽  
Michael E O'Callaghan ◽  
Tina Kopsaftis ◽  
Scott Walsh ◽  
...  

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p <0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 191-191
Author(s):  
Scott J. Parker ◽  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Anitha Alex ◽  
Marta Elise Heilbrun ◽  
...  

191 Background: Progression of bone metastasis in mCRPC is assessed solely by BS findings and correlates modestly with overall survival (OS). Given the lack of reliability of BS findings and the ready availability of routinely performed CT scans, which commonly identify bone metastases, we aimed to better assess progression in bone by integrating BS and CT findings and to explore their association with OS. Methods: Data were obtained from patients treated at the University of Utah receiving docetaxel-based chemotherapy (D) or post-docetaxel therapy with orteronel (O). Patients with both baseline and on-therapy CT and BS within 90 days were eligible for analysis. CT and BS underwent central radiology review for bone lesions by a single radiologist. Progressive disease (PD) was defined as ≥ 1 new lesion. Survival was measured from start of therapy. Cox proportional hazards regression was used to explore potential prognosticators of overall survival (OS). Statistical significance was defined as 2-sided p < 0.05. Therapy was a stratification factor. Results: Twenty-eight patients were evaluable including 18 patients receiving D, and 10 receiving O post-docetaxel. The mean age of these patients was 71.4 years and median (95% CI) overall survival was 18.4 (9.7-35.4) months. Four patients had PD on both BS and CT, while 2 (7%) had PD on CT but not BS and 3 had PD on BS but not CT. Patients with PD on BS or CT had worse OS (HR = 2.68, 95% CI = 1.04-6.90, p = 0.041) than those with no PD on either CT or BS. Looking at individual lesions, 4 (14%) patients had new lesions identified on CT which was not observed using BS, and they were associated with worse OS (HR = 3.72, 1.01-13.66, p = 0.048). Conversely, no significant difference in OS was observed for 4 patients with lesions identified on BS which were not observed using CT (HR = 2.67, 0.58-12.32, p = 0.21). Conclusions: This hypothesis-generating study suggests that CT can complement and enhance the ability of BS to capture PD and predict OS. Integration of BS findings using Prostate Cancer Working Group (PCWG)-3 guidelines to define PD and CT bone findings should be investigated in a larger study as an intermediate endpoint.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e562-e562
Author(s):  
Naoki Fujita ◽  
Takuya Koie ◽  
Hayato Yamamoto ◽  
Atsushi Imai ◽  
Yuki Tobisawa ◽  
...  

e562 Background: We estimated the natural history and predictive factors of oncological outcomes in patients with prostate cancer (PCa) after radical prostatectomy (RP). Methods: In this retrospective study, we reviewed the clinical and pathological records of 1083 PCa patients who underwent RP and bilateral pelvic lymphadenectomy with or without neoadjuvant therapy between July 1996 and December 2014 at Hirosaki University. All patients were followed-up by assessing serum prostate-specific antigen (PSA) and testosterone levels every 3 months for 5 years and every 6 months thereafter. The endpoint was the oncological outcomes after surgery. Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. Results: The 5-year and 10-year overall survival rates were 98.5 % and 92.0 %, respectively. At the end of the study, 226 patients (20.8%) showed biochemical recurrence and 28 patients (2.6%) had developed castration-resistant Pca (CRPC). The patients with CRPC were significantly poor prognosis compared with those without CRPC (P < 0.01). On multivariate analysis, although preoperative variables were no significant differences, only CRPC was significantly associated with OS. Conclusions: RP was shown to provide excellent long-term survival with OS at 10 years. In addition, a small proportion of the patients treated with RP had CRPC and died of Pca within 10 years. Development to castration resistant status may have critical impact on OS.


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]


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 433-433
Author(s):  
Philippe Merle ◽  
Agnes Rode ◽  
Anne-Frederique Manichon ◽  
Nadim Fares ◽  
Celia Prevost ◽  
...  

433 Background: SR is a curative therapy of single HCC. CRT is efficient for small HCC (≤ 5 cm), whereas its combination to TACE (CRT+TACE) is needed for large ( > 5 cm) HCC. However, SR remains the gold-standard in guidelines for large HCC. This work aims to compare these approaches. Methods: Retrospective analysis of prospectively collected data, on patients (pts) included at Lyon North Hepatobiliary Centre, Child-Pugh-A, single HCC. CRT+TACE was decided at the HCC board by ineligibility for SR, radiofrequency or liver transplantation. Outcome of pts was compared between CRT+TACE and SR. Continuous variables were assessed by the t-Student test, and survival analysis by the Cox proportional-hazards regression. Results: 178 pts (68 CRT+TACE, 110 SR), males 78%, cirrhosis 52%, etiology (alcohol 46%, HCV 17%, HBV 13%, NASH 30%), 103 small, 75 large HCC, median age 66 ys, tumor size 50 mm, AFP 8 ng/mL, albuminemia (ALB) 39 g/L, platelets (PLAT) 166 Giga/L, follow-up 33 months. CRT+TACE complete response rate: 92% small / 80% large HCC. Small HCC comparison: CRT+TACE vs SR: age (67 vs 64, P= NS), cirrhosis (94% vs 47%, P< 0.0001), ALB (36 vs 40, P= 0.0001), PLAT (150 vs 201, P= 0.02), AFP (381 vs 300, P= NS). CRT-TACE was a poor outcome factor in univariate analysis for overall survival (OS) (HR 2.32; P= 0.01), progression-free survival (PFS) (HR 1.90; P= 0.007), but did not remain independent in multivariate analysis due to combined factors: age > 70, cirrhosis, ALB < 35, PLAT < 100. Large HCC comparison: CRT+TACE vs SR: age (73 vs 62, P= 0.0008), cirrhosis (70% vs 25%, P= 0.0004), ALB (38 vs 39, P= NS), PLAT (173 vs 240, P= 0.01), AFP (5616 vs 3456, P= NS). CRT-TACE was a poor outcome factor only for OS (HR 3.01; P= 0.0007) in univariate analysis. After adjustment to other factors (age > 70, cirrhosis, PLAT < 100), CRT-TACE was not independent in multivariate analysis for OS ( P= 0.19). Conclusions: CRT+TACE induced an encouraging tumor control rate in a population of older pts, more deteriorated chronic hepatopathy than pts treated by SR. Especially for large HCC, SR was not better than CRT+TACE on the outcome. Prospective randomized trials are warranted to confirm these data.


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]


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