Defining oligometastatic hormone sensitive prostate cancer and clinically significant outcomes: Implications on clinical trials?

2021 ◽  
Author(s):  
Jaime O. Herrera-Caceres ◽  
Alexandra Gleave ◽  
Katherine Lajkosz ◽  
Hanan Goldberg ◽  
Dixon T.S. Woon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Hormone Sensitive ◽  
Clinically Significant

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.

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.

Use of docetaxel in low- and high-burden metastatic hormone-sensitive prostate cancer: A systematic review and assessment of subgroup analyses

2021 ◽  
Vol 27 (7) ◽  
pp. 1743-1750
Author(s):  
Manuel David Gil-Sierra ◽  
Emilio Jesus Alegre-del Rey ◽  
Catalina Alarcon de la Lastra-Romero ◽  
Marina Sánchez-Hidalgo
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Metastatic Disease ◽  
Subgroup Analysis ◽  
Randomised Clinical Trial ◽  
Randomised Clinical Trials ◽  
High Burden ◽  
Subgroup Analyses ◽  
Hormone Sensitive

Background Use of docetaxel in low- and high-burden metastatic hormone-sensitive prostate cancer presents considerable controversy. There is literature suggesting lack of benefit for low-volume of metastases. Objective The study aims to develop a systematic review and methodological assessment of subset analysis about use of docetaxel in metastatic hormone-sensitive prostate cancer regarding volume of metastatic disease. Methods A systematic review in the Pubmed® database was conducted up to 25 September 2020. A reference tracking was also developed. Randomised clinical trials with subgroup analysis according volume of metastatic disease for overall survival were selected. Two methodologies were used. One of them considered statistical interaction of subsets ( p(i) < 0.1), pre-specification, biological plausibility and consistency among subset results of similar randomised clinical trials. The second methodology was a two-part validated tool: preliminary questions to discard subset analysis without minimal relevance and a checklist The checklist provides recommendations for applicability of subgroup analysis in clinical practice. Results A total of 31 results were found in systematic reviews in the Pubmed® database. One result was identified in the reference tracking. Of the total of 32 results, four randomised clinical trials were included in the study. About first methodology, statistical interaction among subgroups was obtained in one randomised clinical trial. Subgroup analysis was pre-specified in two randomised clinical trials. Biological plausibility was reasonable. No external consistency among results of subgroup analyses in randomised clinical trials was observed. Preliminary questions of second methodology rejected applicability of subgroup analysis in three randomised clinical trials. A ‘null’ recommendation for applicability of subset results was obtained in the remaining randomised clinical trial. Conclusions Patients with low- and high-burden metastatic hormone-sensitive prostate cancer would benefit from docetaxel therapy. No consistent differences for overall survival were observed in subgroup analyses regarding volume of metastatic disease.

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.

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