scholarly journals Stratification of Prognoses based on Criteria from Clinical Trials of Metastatic Hormone-sensitive Prostate Cancer

2021 ◽  
Author(s):  
Hyun Kyu Ahn ◽  
Jeong Woo Yoo ◽  
Kyo Chul Koo ◽  
Byung Ha Chung ◽  
Kwang Suk Lee
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Liver Metastasis ◽  
Bone Metastasis ◽  
High Volume ◽  
Classification Systems ◽  
Oncologic Outcomes ◽  
Visceral Metastasis ◽  
Hormone Sensitive ◽  
Low Volume

Abstract Background: Oncologic outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) are extremely heterogeneous. We aimed to (1) stratify the prognosis in mHSPC patients according to criteria for high-volume disease, as defined in clinical trials, and (2) identify the combinations of unfavorable risk factors.Methods: This retrospective study reviewed 623 patients who were diagnosed with mHSPC between 1996 and 2014. The prognoses of mHSPC patients were stratified by criteria from the GETUG15, CHAARTED, STAMPEDE, and LATITUDE trials. The exclusion criteria were incomplete clinical data, docetaxel chemotherapy with upfront options, and metastatic disease without proper management after initial diagnosis.Results: All 485 patients (median follow-up=36.1 months) were categorized according to stage: M1a (70, 14.4%), M1b (367, 75.7%), and M1c (48, 9.9%). Significant differences in overall survival (OS) and cancer-specific survival (CSS) were found among the groups with low-volume disease, as classified by four clinical trials (log-rank p=0.001 and p<0.001, respectively). Bone metastasis volume and liver metastasis were independent predictors of prognosis. According to disease classification under NCCN guidelines, the prognosis of CSS between low-volume disease patients and M1c patients (no bone metastasis and low-volume bone metastasis) was not significantly different. Additionally, the prognosis of CSS did not significantly differ between M1c (high-volume bone metastasis and visceral metastasis, except liver) and M1b (high-volume bone metastasis) patients.Conclusions: The prognoses of patients with low-volume disease, based on several classification systems, were heterogeneous. Except for lung or liver metastasis, the combination of visceral metastasis with no/low-volume bone disease should be considered as a proxy of less aggressive disease in patients presenting with mHSPC.

scholarly journals Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial

2018 ◽  
Vol 36 (11) ◽  
pp. 1080-1087 ◽  
Author(s):  
Christos E. Kyriakopoulos ◽  
Yu-Hui Chen ◽  
Michael A. Carducci ◽  
Glenn Liu ◽  
David F. Jarrard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Volume ◽  
Phase Iii ◽  
Cancer Trial ◽  
Term Survival ◽  
Chemohormonal Therapy ◽  
Androgen Ablation ◽  
Hormone Sensitive ◽  
Low Volume

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

scholarly journals Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

2020 ◽  
pp. 882-897 ◽  
Author(s):  
Clare Gilson ◽  
Fiona Ingleby ◽  
Duncan C. Gilbert ◽  
Marina A. Parry ◽  
Nafisah B. Atako ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
Pi3k Pathway ◽  
Mismatch Repair Gene ◽  
Copy Number Loss ◽  
Hormone Sensitive ◽  
Low Volume

PURPOSE The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor ( AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences ( AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

Evolving Treatment of Oligometastatic Hormone-Sensitive Prostate Cancer

2017 ◽  
Vol 13 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Jessica M. Clement ◽  
Christopher J. Sweeney
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Androgen Deprivation Therapy ◽  
High Volume ◽  
Androgen Deprivation ◽  
Durable Response ◽  
Ablative Therapies ◽  
Node Positive Disease ◽  
Hormone Sensitive

Oligometastatic disease was postulated by Hellman and Weichselbaum in 1995 to be a disease state that may reflect a time point in the malignant process that may be amenable to local therapies to allow for patients to achieve a durable response or possible cure despite having advanced disease. Aggressive metastasis-directed therapy has been used in malignancies such as renal cell carcinoma, non–small-cell lung cancer, and colorectal cancer with some evidence of long-term benefit in selected patients. Recently, it has been proposed that some men with oligometastatic hormone-sensitive prostate cancer may also benefit from metastasis-directed therapy. As with most malignancies, optimal therapy for prostate cancer relies on multimodal therapy, best highlighted by the survival benefit seen in high-volume metastatic prostate cancer with the addition of docetaxel to androgen-deprivation therapy. This is becoming increasingly evident for oligometastatic prostate cancer, with emerging data sets suggesting a possible benefit of local ablative therapies for metastatic lesions combined with androgen-deprivation therapy. However, the bulk of the data is retrospective and thus subject to bias. Ongoing clinical trials are evaluating combination therapy to help elucidate the role of each therapy separately and together to determine optimal interventions for this population. This clinical review discusses the retrospective data evaluating local therapies such as radiation and surgery in men with lymph node–positive disease, as well as limited bone metastases, and outlines ongoing, prospective clinical trials designed to further investigate the role of multimodality therapy in the outcomes of men with oligometastatic hormone-sensitive prostate cancer.

Androgen-deprivation therapy plus docetaxel-based chemotherapy in metastatic hormone-sensitive prostate cancer. A meta-analysis of randomized clinical trials.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 188-188 ◽  
Author(s):  
Allan Ramos-Esquivel ◽  
Joao M. Baptista ◽  
Luis Corrales-Rodriguez ◽  
Ileana Gonzðlez ◽  
Melissa Juarez Villegal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Androgen Deprivation ◽  
Cochrane Central Register ◽  
Newly Diagnosed ◽  
Hormone Sensitive

188 Background: Androgen-deprivation therapy (ADT) is the standard of treatment for patients with newly diagnosed metastatic prostatic cancer. Nevertheless, recent trials have suggested a role for chemotherapy in these patients. We performed a systematic review and meta-analysis to assess the efficacy and safety of docetaxel-based chemotherapy in combination with ADT for patients with hormone-sensitive metastatic prostate cancer. Methods: Randomized clinical trials (RCT) were identified after systematic searching of electronic databases (MEDLINE, OVID and The Cochrane Central Register of Controlled Trials), as well as ASCO conference proceedings from 2010 to 2015. We included only RCT comparing ADT versus the combination of ADT plus docetaxel-based chemotherapy in patients with newly diagnosed metastatic prostate cancer. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes: overall survival (OS) and clinical progression-free survival (PFS), according to the inverse-variance method. Heterogeneity was measured using the Q and I2statistics. Results: Three RCT (n = 2 262), were included in our meta-analysis (E3805, GETUG-AFU 15 and the M1 subgroup from STAMPEDE Trial). Docetaxel-based chemotherapy plus ADT was associated with improved OS (HR: 0.74; 95% CI: 0.60-0.90; p = 0.003). The heterogeneity of these trials was moderate (Tau2: 0.02; I2: 51%; p = 0.13). Clinical PFS was also significantly better in patients receiving docetaxel-based chemotherapy (HR: 0.67; 95% CI 0.55-0.82; p = 0.0001), with moderate between-study heterogeneity detected (Tau2: 0.01; I2: 42%; p = 0.19). Different subset of patients in these trials can explain the aforementioned heterogeneity. Regarding adverse drug reactions grade 3 or higher, neutropenia was reported in a range from 36% in the GETUG-AFU 15 Trial to 12% in the STAMPEDE trial and febrile neutropenia was reported from 6.1% in the E3805 Trial to 12% in the STAMPEDE Trial. Conclusions: The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS. New trials are needed to determine which patients benefit the most from this intervention.

Cost-effectiveness of upfront therapeutic options in low-volume de novo metastatic hormone-sensitive prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 211-211
Author(s):  
Neil Rohit Parikh ◽  
Eric M. Chang ◽  
Nicholas George Nickols ◽  
Matthew Rettig ◽  
Ann C. Raldow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Cost Effectiveness ◽  
Systemic Therapy ◽  
De Novo ◽  
Cost Effective ◽  
Therapeutic Options ◽  
Oral Drug ◽  
Hormone Sensitive ◽  
Low Volume

211 Background: Low-volume de novo metastatic hormone-sensitive prostate cancer (mHSPC) has historically been treated with lifelong androgen deprivation therapy (ADT). Recently, however, the addition of several advanced therapeutic options – radiation therapy (RT) to the primary, advanced hormonal therapy agents such as abiraterone acetate/prednisone (AAP), and chemotherapy – to ADT have been shown to improve survival in low-volume mHSPC. The objective of this study was to compare the cost-effectiveness of treating low-volume mHSPC patients upfront with RT+ADT, AAP+ADT, or docetaxel+ADT. Methods: A Markov-based cost-effectiveness analysis was constructed comparing three treatment strategies for low-volume mHSPC patients: (1) upfront RT+ADT --> salvage AAP+ADT --> salvage docetaxel+ADT; (2) upfront AAP+ADT --> salvage docetaxel+ADT, and (3) upfront docetaxel+ADT --> salvage AAP+ADT. Transition probabilities were calculated using data from STAMPEDE arms C/G/H, COU-AA-301, COU-AA-302, and TAX-327. RT was delivered via five-fraction stereotactic body radiation therapy. The analysis utilized a 10-year time horizon, and a $100,000/quality adjusted life year (QALY) willingness-to-pay threshold. Utilities were extracted from the literature; costs were taken from Medicare fee schedules and VA oral drug contracts. Results: At 10 years, total cost was $140K, $259K, and $189K, with total QALYs of 4.66, 5.03, and 3.72 for strategies (1) upfront RT+ADT, (2) upfront AAP+ADT, and (3) upfront docetaxel+ADT, respectively. Compared to upfront RT+ADT, upfront AAP+ADT was not cost-effective (ICER: $321K/QALY). This result remained unchanged even after modification of various model inputs in 1-way sensitivity analysis. Upfront docetaxel+ADT was both more costly and less effective than upfront RT+ADT (ICER: -$53K/QALY). Conclusions: At 10 years, RT+ADT is cost-effective compared to other advanced systemic therapy options alone, and should be considered as a viable treatment strategy in all patients with a low-burden of metastatic disease. Additional studies are needed to determine whether any benefit exists in combining RT to the primary with upfront advanced systemic therapy.

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