scholarly journals Oncological outcomes of metastatic castration resistant prostate cancer (mCRPC) treated with different therapies sequences after completion of docetaxel: a retrospective study in Songklanagarind Hospital

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.

2020 ◽  
Author(s):  
Takashi Kawahara ◽  
Yusuke Saigusa ◽  
Shuko Yoneyama ◽  
Masashi Kato ◽  
Ippei Kojima ◽  
...  

Abstract BACKGROUND:With widespread medication choices for metastatic castration-resistant prostate cancer (mCRPC) is now available, on the other hand biomarker to predict the efficacy of each mCRPC treatment has not been established.Objective:This study developed prognostic nomogram to predict prognosis in CRPC patients who received abiraterone acetate (ABI) and/or enzalutamide (ENZ).Design, Setting, and Participants:A total of 568 mCRPC patients received ABI and/or ENZ from 2012 to 2017 were enrolled in this study. We developed prognostic nomogram based on the risk factors by Cox proportional hazards regression model.Outcome Measurements and Statistical Analysis:The nomogram was also assessed for discriminatory ability with the concordance index (C-index). We repeated 5-fold cross-validation 2000 times to estimate the C-index and reported the means of the estimated C-index for the training and validation sets. And we also developed nomogram application software (app) based on this nomogram.Results and Limitations:The median overall survival (OS) was 24.7 months. A multivariable analysis showed that the time to CRPC, pre-chemotherapy, baseline PSA, baseline ALP, and baseline LDH were independent risk factors for the OS (HR: 0.521, 1.681, 1.439, 1.827, 12,123, p:0.001, 0.001, <0.001, 0.019, <0.001)). C-index was 0.72 in training cohort and 0.71 in validation cohort.CONCLUSIONS:We developed nomograms to predict the OS for Japanese mCRPC patients who received ABI and/or ENZ. The advent of mCRPC prognosis prediction app will facilitate greater accessibility for clinical use.Patient SummaryThis study developed and validated a nomogram for predicting the prognosis of mCRPC patients who receive ABI/ENZ treatment using clinical information. This study also developed mobile app to facilitate clinical usage.


2020 ◽  
Author(s):  
Takashi Kawahara ◽  
Yusuke Saigusa ◽  
Shuko Yoneyama ◽  
Masashi Kato ◽  
Ippei Kojima ◽  
...  

Abstract Background:With widespread medication choices for metastatic castration-resistant prostate cancer (mCRPC) is now available, on the other hand biomarker to predict the efficacy of each mCRPC treatment has not been established.Objective:This study developed prognostic nomogram to predict prognosis in CRPC patients who received abiraterone acetate (ABI) and/or enzalutamide (ENZ).Design, Setting, and Participants:A total of 568 mCRPC patients received ABI and/or ENZ from 2012 to 2017 were enrolled in this study. We developed prognostic nomogram based on the risk factors by Cox proportional hazards regression model.Outcome Measurements and Statistical Analysis:The nomogram was also assessed for discriminatory ability with the concordance index (C-index). We repeated 5-fold cross-validation 2000 times to estimate the C-index and reported the means of the estimated C-index for the training and validation sets. And we also developed nomogram application software (app) based on this nomogram.Results and Limitations:The median overall survival (OS) was 24.7 months. A multivariable analysis showed that the time to CRPC, pre-chemotherapy, baseline PSA, baseline ALP, and baseline LDH were independent risk factors for the OS (HR: 0.521, 1.681, 1.439, 1.827, 12,123, p:0.001, 0.001, <0.001, 0.019, <0.001)). C-index was 0.72 in training cohort and 0.71 in validation cohort.Conclusion:We developed nomograms to predict the OS for Japanese mCRPC patients who received ABI and/or ENZ. The advent of mCRPC prognosis prediction app will facilitate greater accessibility for clinical use.Patient SummaryThis study developed and validated a nomogram for predicting the prognosis of mCRPC patients who receive ABI/ENZ treatment using clinical information. This study also developed mobile app to facilitate clinical usage.


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.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 28-28
Author(s):  
Caroline F. Pratz ◽  
Robert A. Brodsky ◽  
Emmanuel S. Antonarakis

28 Background: Anticoagulants have been postulated to possess antitumor activity, although clinical data supporting this claim are conflicting. We sought to examine the effect of therapeutic anticoagulation on OS in men with mCRPC receiving first-line docetaxel chemotherapy. Methods: We retrospectively reviewed the records of 247 consecutive mCRPC patients who received first-line docetaxel chemotherapy between 1/1/1998 and 1/1/2010. Information on anticoagulant use, type of anticoagulant administered, indication for anticoagulation, and duration of anticoagulation were captured. Univariate and multivariable Cox proportional hazards regression models were developed to investigate the effect of anticoagulant use on OS. Results: In all, 29/247 men (11.7%) received anticoagulation (LMW heparin: 17/247; warfarin: 12/247). The indication was DVT in 15/247, PE in 9/247, and both DVT and PE in 5/247 men. In univariate analysis, anticoagulant use was associated with improved OS (any anticoagulant, HR 0.61 [95%CI 0.40–0.94] P=0.024; LMW heparin, HR 0.58 [95%CI 0.34–0.99] P=0.048; warfarin, HR 0.82 [95%CI 0.55–1.28] P=0.23). Median OS was 20.9 mo (with any anticoagulant) versus 17.1 mo (with no anticoagulant). In multivariable analysis, anticoagulant use remained a significant predictor of OS after adjusting for other prognostic factors (Table). Conclusions: Anticoagulant use is an independent predictor of OS in men with mCRPC receiving docetaxel. This finding is surprising given that the occurrence of venous thrombosis might be expected to negatively influence OS. If validated, these data may provide the impetus to explore the antitumor potential of anticoagulants in prospective clinical trials. [Table: see text]


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.


2018 ◽  
Vol 12 (8) ◽  
Author(s):  
Daniel W. Yokom ◽  
John Stewart ◽  
Nimira S. Alimohamed ◽  
Eric Winquist ◽  
Scott Barry ◽  
...  

Introduction: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel.Methods: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response.Results: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response, or primary PSA progression.Conclusions: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.


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