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Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer.

ABSTRACT: We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors.Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC.

SUBMITTER: Narita S

PROVIDER: S-EPMC6700107 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer.

Narita Shintaro S Nomura Kyoko K Hatakeyama Shingo S Takahashi Masahiro M Sakurai Toshihiko T Kawamura Sadafumi S Hoshi Senji S Ishida Masanori M Kawaguchi Toshiaki T Ishidoya Shigeto S Shimoda Jiro J Sato Hiromi H Mitsuzuka Koji K Tochigi Tatsuo T Tsuchiya Norihiko N Ohyama Chikara C Arai Yoichi Y Nagashima Kengo K Habuchi Tomonori T

Scientific reports 20190819 1

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specifi ...[more]

PMID: 31427687

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Project description:ObjectivesTo evaluate the prognosis of newly diagnosed patients with metastatic hormone-naïve prostate cancer (mHNPC) and develop a novel prognostic model based on ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) risk classifications.Patients and methodsWe retrospectively analyzed the data of 578 newly diagnosed mHNPC patients initially treated with androgen deprivation therapy. We evaluated three clinical factors, namely, CHAARTED risk classifications (high-volume disease [HVD] vs low-volume disease [LVD]), Gleason scores (GS, 9-10 vs ≤8), and hemoglobin (Hb, ≤13.0 g/dL vs >13.0 g/dL), for their prognostic potential in predicting time to castration-resistant prostate cancer (TTC) and overall survival (OS) of mHNPC patients by multivariate analysis. Moreover, we developed a novel prognostic model that consisted of significant prognostic factors.ResultsOf the entire cohort, the median TTC and OS values were 18.3 and 67.5 months, respectively. HVD, GS 9-10, and Hb ≤13.0 g/dL were independent poor prognostic factors for both TTC and OS. We developed a novel prognostic model which could stratify mHNPC patients into four risk groups according to the numbers of poor prognostic factors: group 1, LVD with low-risk (LVD patients without GS 9-10 and Hb ≤13.0 g/dL); group 2, LVD with high-risk (LVD patients with GS 9-10, Hb ≤13.0 g/dL, or both); group 3, HVD with low-risk (HVD patients without GS 9-10 with or without Hb ≤13.0 g/dL); and group 4, HVD with high-risk (HVD patients with GS 9-10 with or without Hb ≤13.0 g/dL). The median TTC and OS of groups 1, 2, 3, and 4 were 124.8, 36.4, 17.9, and 11.2 months, and 117.2, 94.2, 67.9, and 46.2 months, respectively. A significant difference in TCC and OS was found between all groups.ConclusionWe developed a prognostic model for mHNPC patients that consisted of CHAARTED risk classifications, GS, and Hb. Our prognostic model could significantly stratify the prognosis of patients with LVD and HVD into two groups each. This model might be a good reference for shared decision making between patients and physicians on the initial treatment for mHNPC.

Project description:ImportanceProstate radiation therapy (PRT) is a treatment option in men with low-volume metastatic prostate cancer based on the results of the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy Arm H (STAMPEDE-H) trial. However, the cost-effectiveness of this treatment remains unaddressed.ObjectiveTo assess the cost-effectiveness of PRT when added to androgen deprivation therapy (ADT) for men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC).Design, setting, and participantsThis economic evaluation used microsimulation modeling to evaluate the cost-effectiveness of adding PRT to ADT. A simulated cohort of 10 000 individuals with low-volume mHSPC was created. Data from men with low-volume mHSPC were extracted and analyzed from January 18, 2019, through July 4, 2020. Transition probabilities were extracted from the STAMPEDE-H study. Health states included stable disease, progression, second progression, and death. Individual grade 2 or higher genitourinary and gastrointestinal toxic events associated with PRT were tracked. Univariable deterministic and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions. Health state utility estimates were based on the published literature.ExposuresThe combination of PRT and ADT using regimens of 20 fractions and 6 weekly fractions.Main outcomes and measuresOutcomes included net quality-adjusted life-years (QALYs), costs in US dollars, and incremental cost-effectiveness ratios. A strategy was classified as dominant if it was associated with higher QALYs at lower costs than the alternative and dominated if it was associated with fewer QALYs at higher costs than the alternative.ResultsFor the base case scenario of men 68 years of age with low-volume mHSPC, the modeled outcomes were similar to the target clinical data for overall survival, failure-free survival, and rates of PRT-related toxic effects. The addition of PRT was a dominant strategy compared with ADT alone, with a gain of 0.16 QALYs (95% CI, 0.15-0.17 QALYs) and a reduction in net costs by $19 472 (95% CI, $23 096-$37 362) at 37 months of follow-up and a gain of 0.81 QALYs (95% CI, 0.73-0.89 QALYs) and savings of $30 229 (95% CI, $23 096-$37 362) with lifetime follow-up.Conclusions and relevanceIn the economic evaluation, PRT was a dominant treatment strategy compared with ADT alone. These findings suggest that addition of PRT to ADT is a cost-effective treatment for men with low-volume mHSPC.

Project description:BackgroundMetastatic breast cancer (MBC) is a challenging disease, and despite new therapies, prognosis is still poor for a majority of patients. There is a clinical need for improved prognostication where immuno-oncology markers can provide important information. The aim of this study was to evaluate serum immuno-oncology markers in MBC patients and their respective relevance for prediction of survival.Patients and methodsWe investigated a broad panel of 92 immuno-oncology proteins in serum from 136 MBC patients included in a prospective observational study (NCT01322893) with long-term follow-up. Serum samples were collected before start of systemic therapy and analyzed using multiplex proximity extension assay (Olink Target 96 Immuno-Oncology panel). Multiple machine learning techniques were used to identify serum markers with highest importance for prediction of overall and progression-free survival (OS and PFS), and associations to survival were further evaluated using Cox regression analyses. False discovery rate was then used to adjust for multiple comparisons.ResultsUsing random forest and random survival forest analyses, we identified the top nine and ten variables of highest predictive importance for OS and PFS, respectively. Cox regression analyses revealed significant associations (P < 0.005) of higher serum levels of IL-8, IL-10 and CAIX with worse OS in multivariable analyses, adjusted for established clinical prognostic factors including circulating tumor cells (CTCs). Similarly, high serum levels of IL-8, IL-10, ADA and CASP8 significantly associated with worse PFS. Interestingly, high serum levels of FasL significantly associated with improved OS and PFS. In addition, CSF-1, IL-6, MUC16, TFNSFR4 and CD244 showed suggestive evidence (P < 0.05) for an association to survival in multivariable analyses. After correction for multiple comparisons, IL-8 still showed strong evidence for correlation to survival.ConclusionTo conclude, we found six serum immuno-oncology markers that were significantly associated with OS and/or PFS in MBC patients, independently of other established prognostic factors including CTCs. Furthermore, an additional five serum immuno-oncology markers provided suggestive evidence for an independent association to survival. These findings highlight the relevance of immuno-oncology serum markers in MBC patients and support their usefulness for improved prognostication. Trial registration Clinical Trials (NCT01322893), registered March 25, 2011.

Dataset Information

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer.

Publications

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer.

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