scholarly journals Effect of Chemotherapy on Overall Survival in Contemporary Metastatic Prostate Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Benedikt Hoeh ◽  
Christoph Würnschimmel ◽  
Rocco S. Flammia ◽  
Benedikt Horlemann ◽  
Gabriele Sorce ◽  
...  

IntroductionRandomized clinical trials demonstrated improved overall survival in chemotherapy exposed metastatic prostate cancer patients. However, real-world data validating this effect with large scale epidemiological data sets are scarce and might not agree with trials. We tested this hypothesis.Materials and MethodsWe identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results (SEER) database (2014-2015). Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed patients vs chemotherapy-naïve patients. All analyses were repeated in propensity-score matched cohorts. Additionally, landmark analyses were applied to account for potential immortal time bias.ResultsOverall, 4295 de novo metastatic prostate cancer patients were identified. Of those, 905 (21.1%) patients received chemotherapy vs 3390 (78.9%) did not. Median overall survival was not reached at 30 months follow-up. Chemotherapy-exposed patients exhibited significantly better overall survival (61.6 vs 54.3%, multivariable HR:0.82, CI: 0.72-0.96, p=0.01) at 30 months compared to their chemotherapy-naïve counterparts. These findings were confirmed in propensity score matched analyses (multivariable HR: 0.77, CI:0.66-0.90, p<0.001). Results remained unchanged after landmark analyses were applied in propensity score matched population.ConclusionsIn this contemporary real-world population-based cohort, chemotherapy for metastatic prostate cancer patients was associated with better overall survival. However, the magnitude of overall survival benefit was not comparable to phase 3 trials.

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034331 ◽  
Author(s):  
Yu Guang Tan ◽  
Leonard Pang ◽  
Farhan Khalid ◽  
Randy Poon ◽  
Hong Hong Huang ◽  
...  

ObjectiveTo evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore.DesignRetrospective analysis of a large prospective Uro-oncology registry of mPCa.SettingThis study is carried out in a tertiary hospital in Singapore.ParticipantsWe reviewed our institution’s prospectively maintained database of 685 patients with mPCa over a 20-year period (1995–2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded.Primary and secondary outcome measuresThe primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years.Results237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50 g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7–27). The median overall survival was 45 months (IQR 20–63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995–1999) to 47.8 months (2010–2014) (p<0.01).ConclusionMorbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 258-258
Author(s):  
Kanika Gupta ◽  
Antoine Nafez Finianos ◽  
Brandon Clark ◽  
Samuel J. Simmens ◽  
Jeanny B. Aragon-Ching

258 Background: We reported initial findings on the phenotypic differences between de novo versus primary progressive metastatic prostate cancer (Finianos et al., ASCO GU; abstr 285). We sought to determine the differences in the phenotypic characteristics of these 2 cohorts of patients and update the data with overall survival and patterns of response to androgen deprivation therapy (ADT) in patients presenting with de novo versus primary progressive prostate cancer. Methods: A retrospective chart review in a single-institution center for a period of 2 years was undertaken. Phenotypic characteristics included age at diagnosis, race, overall survival, treatment patterns, and response to ADT. Analysis was by t-test, Mann-Whitney U test, and Fisher’s Exact test. Results: A total of 90 patients were included in this cohort with de novo, dn (n = 38) and primary progressive, pp (n = 52) patients. There were no significant differences between the 2 cohorts with regard to the median age at diagnosis (dn = 66, pp = 61, p = 0.11), alkaline phosphatase level (dn = 135.5, pp = 86, p = 0.27), BMI (dn = 28.47, pp = 27, p = 0.78), creatinine (dn = 1.02, pp = 0.99, p = 0.34), LDH (dn = 188, pp = 166, p = 0.34), and testosterone on metastasis (dn = 276, pp = 31, p = 0.16). However, de novo cancers were diagnosed with higher mean gleason scores (dn = 8.36, pp = 7.7, p = 0.004), had higher median PSA upon diagnosis (dn = 63.1, pp = 8.8, p < .0001) and higher PSA on metastasis (dn = 61.7, pp = 12.5, p = .0002), and had a statistically significant decreased duration of hormone sensitivity (dn = 642 days, pp = 1783 days, p = < .0001). Patients with d e novo cancers also had a shorter median survival than primary progressive cancers (dn = 2257 days, pp = 4217 days, p = 0.02). Conclusions: Patients who present with de novo metastatic prostate cancer appear to develop early castration resistance and have worse overall survival than those who present with primary progressive disease. We are exploring the molecular differences in terms of androgen receptor expression as a potential etiology for development of early castration resistance.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 201-201 ◽  
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
Richard M. Lee-Ying

201 Background: Recent trials have shown that apalutamide and enzalutamide can improve metastasis free survival (MFS) in advanced non-metastatic (M0) castrate-resistant prostate cancer (CRPC). MFS is a novel clinical endpoint, demonstrated to be a strong predictor of overall survival (OS) for localized prostate cancer, yet it is unknown if this is also true for M0 CRPC. Our aim was to determine how strongly MFS in M0 CRPC correlates with OS in a real world population. Secondary analyses evaluated whether a rapid PSA-doubling time (PSADT), of ≤10 months, impacts outcomes. Methods: We performed an analysis of patients diagnosed with advanced prostate cancer, followed at the Tom Baker Cancer Centre, in Calgary, Alberta from 2001-2017. Patients were excluded if they did not develop M0 CRPC. MFS and OS were measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes based on PSADT. Correlation between OS and MFS was determined using Pearson Correlation and Kendall’s Tau-B. Results: A total of 1310 patients were identified with advanced prostate cancer, of which 87 developed M0 CRPC. The median age of diagnosis of M0 CRPC was 72 years, with a median Gleason score of 7.0, initial PSA of 10.4, and PSADT of 5.1 months. Only 6 patients were treated with second-generation anti-androgens or chemotherapy. Median MFS and OS after M0 CRPC diagnosis were 44.1 and 83.7 months, respectively. Pearson Correlation between MFS and OS was strong with a coefficient of 0.850 (p < 0.001); with non-parametric Kendall’s Tau, correlation was also strong with a coefficient of 0.632 (p < 0.001). PSADT ≤10 months was identified in 70 patients, and associated with a significantly shorter MFS, compared to a PSADT > 10 months (40.2 vs. 90.4 months; p = 0.001), as well as shorter OS (76.2 vs. 104.3 months; p = 0.008). Conclusions: MFS for M0 CRPC is strongly correlated with OS in a real world population. PSADT of ≤10 months seems to be a useful prognostic tool in estimating MFS and OS in patients with M0 CRPC. MFS was better than expected even in patients with a PSADT of ≤10 months, which may due to our adherence to the biochemical definition of castration-resistant disease, as well as lack of standard imaging intervals in the real world.


2019 ◽  
Vol 5 (suppl) ◽  
pp. 13-13
Author(s):  
Po-Jung SU ◽  
Yu-Ann Fang ◽  
Yung-Chun Chang ◽  
Yung-Chia Kuo ◽  
Yung-Chang Lin

13 Background: For de novo metastatic prostate cancer (mPC)) patients, their prognosis may be really different. Some of these patients response very well to hormone therapy with durable survival, but others may be not. For those poor prognosis patients, if we could predict them as high risk patients when diagnosed, and provide aggressive upfront chemotherapy or novel hormonal therapy, they might get better treatment outcomes. Methods: We used data of prostate cancer patients from 2000 to 2016 in Chang Gung Research Database. There are 799 de novo mPC patients with castration. We predicted the possibility for these patients progressed to metastatic castration-resistant prostate cancer (mCRPC) in 1 year and find the high risk group patients. Then we figured out the best features for prediction from the best classifier with Recursive Feature Elimination. Results: The de nove mPC patients who pregressed to mCRPC in 1 year, whose mOS is 21.9 months is worse than who progressed to mCRPC beyond 1 year significantly, whose mOS is 80.7 months. (adjusted hazard ratio[aHR]: 6.43, P<0.001). The overall performance of machine learning by XGBoost is the best in all predictive models for high risk patients. (AUC=0.7000, Accuracy=0.7143). We excluded the features with missing data over 50%, then put all other features in the model. (AUC=0.7042, Accuracy=0.7239). But we got the best performance with only 11 features, including age, time from diagnosis to castration, nadir PSA, hemoglobin, eosinophil/white blood cell ratio, alkaline phosphatase, alanine transaminase, blood urea nitrogen, creatinine, prothrombin time, and secondary primary cancer, by Recursive Feature Elimination. (AUC=0.7131, Accuracy=0.7267). Conclusions: We found the predictive model has better predictive accuracy and shorter manuscript time with less features selected by Recursive Feature Elimination.We can predict high risk group in de novo mPC patients and make better clinical decision for treatment with this XGBoost model.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 33-33 ◽  
Author(s):  
Jessica Strock ◽  
Kathryn P. Gray ◽  
Mari Nakabayashi ◽  
Carolyn Evan ◽  
Elizabeth O'Donnell ◽  
...  

33 Background: Less than 5% of men in a PSA screened population present with denovo metastatic prostate cancer. We sought to characterize the clinical characteristics and survival of this unique group of men. Methods: Retrospective analysis of an institutional data-base – Dana Farber Cancer Institute - Prostate Clinical Research Information Systems (CRIS). All men with metastatic disease as their first presentation of prostate cancer were identified. Patient and disease characteristics were summarized descriptively. The distributions of the study endpoints were estimated using the Kaplan-Meier method with median and 95%CI reported. Results: The analytic cohort has 185 patients with a median follow-up of 7.8 years (95% CI:7.5,11.1) and 94% diagnosed after 1998. Median age at diagnosis is 62 years (Range: 42-86); PSA at diagnosis: Median (Q1-Q3) - 100.2 (23.0, 346.0). Metastases: 97% bone, 2% liver, 2% lung, 8% lymph node. The median time from metastasis diagnosis to start of androgen deprivation therapy (ADT) was 26 days, 139 of those who started ADT had subsequently started treatment for castration resistant prostate cancer (CRPC) - 2nd line hormonal therapy and/or chemotherapy. The median time from ADT to subsequent therapy for CRPC is 14 months with 95% (CI:12,16). 128 patients have died and the median overall survival is 48 months (95% CI:40, 51). Conclusions: This unique cohort of patients at a referral institution tend to be younger and have an overall survival comparable to outcomes in modern day randomized hormone sensitive prostate cancer studies. Assessment of similar group in a multivariate analysis of a prospective trial is needed to confirm this observation. If confirmed, the data would suggest the responsiveness to therapy drives outcome rather than development of metastasis with or without a previously treated primary.


Author(s):  
Christoph Würnschimmel ◽  
Mike Wenzel ◽  
Claudia Collà Ruvolo ◽  
Luigi Nocera ◽  
Zhe Tian ◽  
...  

Abstract Purpose To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate. Methods We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians. Results After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p < 0.001). In OCM adjusted multivariable analyses, Asian race/ethnicity was associated with lower CSM (HR 0.66, CI 0.52–0.83, p < 0.001). Conversely, African-American and Hispanic/Latino race/ethnicity did not affect CSM. OCM rates were comparable between examined races/ethnicities. Conclusion In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients.


Author(s):  
Manato Kanesaka ◽  
Shinichi Sakamoto ◽  
Yasutaka Yamada ◽  
Junryo Rii ◽  
Maihulan Maimaiti ◽  
...  

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