Impact of germline DNA-repair gene BRCA2 and CHEK2 mutations on time to castration resistance in patients with metastatic hormone-naïve prostate cancer: A single center analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5056-5056
Author(s):  
Vsevolod Borisovich Matveev ◽  
Liudmila Lyubchenko ◽  
Andrey Kirichek
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Median Time ◽  
Germline Mutations ◽  
Castration Resistance ◽  
First Line ◽  
Chek2 Mutation ◽  
Mutation Carriers ◽  
Significant Difference ◽  
The Impact

5056 Background: Germline mutations in DNA repair genes are common in patients with andvanced and metastatic prostate cancer (mPCa). Although BRCA mutation carriers have worse outcomes than noncarriers when conventionally treated for local or locally advanced PCa, recent studies reported conflicting results regarding their aggressiveness in patients with advanced disease. This study aimed to examine the impact of germline BRCA1/2 and CHEK2 mutations on time to castration-resistance in patients with mPCa, receiving hormonal androgen deprivation therapy (ADT). Methods: A total of 76 patients with hormone-naive mPCa treated with first line ADT by luteinizing hormone-releasing hormone analogue (LHRHa) between 2014 and 2017 were recruited. Median follow-up was 34,8 mo. We focused on age, volume of metastatic spread, histologic grade, family history. All patients were genotyped for germline mutations in the BRCA1, BRCA2 and CHEK2 genes by polymerase chain reaction real-time and the Sanger sequencing. We used the standard definition of castration-resistance PCa (CRPC). Median time to CRPC were estimated using the Kaplan-Meier method, generated curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA1/2 and CHEK2 mutations. Results: Pathogenic and likely pathogenic germline mutations in the BRCA2 and CHEK2 gene were identified in 19 (25 %) patients. No cases of BRCA1 mutations were detected. Median time to CRPC was significantly shorter in BRCA2 and CHEK2 mutation carriers (7.9 mo, 95 % confidence interval (CI) 2.6 – 13.3), than in non-carriers (48.7 mo, 95 % CI 31.1 – 68.3, p < 0,001). There was no significant difference in median time to CRPC in BRCA2 (7.9 mo, 95 % CI 0.0 - 16.3) and CHEK2 mutation carriers (6.1 mo, 95 CI 5.0 - 7.2, p = 0,448) meanwhile both were shorter than in non-carriers (p = 0.002 and < 0,001). Multivariate analysis confirmed both BRCA2 (hazard ratio [HR]: 2.63; 95 CI 1.32-5.26, p = 0.006) and CHEK2 (HR 6.66, 95 CI 2.35-18.89, p < 0.001) mutations as an independent prognostic factor for time to CRPC, particularly in mPCa with low-volume metastatis spread (HR 3.09, 95 % CI 1.36–7.05, р = 0.007 and HR 14.1, 95 % CI 3.65-54.4, p < 0.001). Conclusions: BRCA2 and CHEK2 carriers had worse outcomes (shortened time to CRPC) than noncarriers when conventionally treated for metastatic PCa by standard first-line hormone treatment with LHRHa.

The impact of time-to-castration resistance on survival in patients with metastatic hormone-naïve prostate cancer: A multicenter retrospective study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 213-213
Author(s):  
Teppei Okamoto ◽  
Shingo Hatakeyama ◽  
Masahiro Takahashi ◽  
Shintaro Narita ◽  
Masanori Ishida ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Prognostic Impact ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
First Line ◽  
Cox Regression Analysis ◽  
Line Life ◽  
Number Of Patients ◽  
The Impact

213 Background: To evaluate the prognostic impact of time to castration resistance (TCR) in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: We retrospectively evaluated 283 mHNPC patients with metastatic castration-resistant prostate cancer (mCRPC) who were initially treated with androgen deprivation therapy as metastatic hormone-naïve prostate cancer in 14 hospitals between September 2008 and October 2018. Overall survival (OS) and OS after castration resistance (OS-CR) were compared between the <12 months (TCR <12M) and ≥12 months (TCR ≥12M). The association between the first-line life-prolonging therapy (docetaxel or new androgen receptor-targeted agents: ART) and TCR on OS-CR was investigated using multivariate Cox regression analysis via inverse probability of treatment weighting (IPTW) model. Results: Median age and time to CRPC were 72 years and 12 months, respectively. The number of patients in the TCR<12M and ≥12M groups were 137 and 146, respectively. Of 283, baseline parameters such as age, extent of disease (EOD), hemoglobin (Hgb), lactate dehydrogenase (LDH), and serum albumin levels were significantly differences in between the groups. We observed significantly poor OS and OS-CR in the TCR <12M group than those in the TCR ≥12M group. First-line docetaxel therapy did not significantly improved OS-CR regardless of TCR. Background (age, ECOG PS, GS, Hgb, tumor volume, serum data, and TCR)-adjusted multivariate Cox regression analyses showed that first-line docetaxel therapy was significantly associated with shorter OS-CR than first-line ART therapy in the TCR <12M group. Conclusions: The prognostic impact of TCR on OS was significant. However, the association between the first-line life-prolonging therapy and TCR on OS need further study.

Effect of germline DNA repair gene mutations on outcomes in men with metastatic castration-resistant prostate cancer receiving first-line abiraterone and enzalutamide.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 221-221
Author(s):  
Emmanuel S. Antonarakis ◽  
Changxue Lu ◽  
Brandon Luber ◽  
Hao Wang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Germline Mutations ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Repair Gene ◽  
Castration Resistant ◽  
Dna Repair Gene

221 Background: Inherited DNA repair gene mutations are more prevalent in men with advanced prostate cancer than previously thought, but their clinical implications are not fully understood. Here we investigated the clinical significance of germline DNA repair gene alterations in men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line novel hormonal therapy (NHT), with a particular emphasis on BRCA1/2 and ATM mutations. Methods: We interrogated 50 DNA repair genes for pathogenic or likely pathogenic germline mutations using leukocyte DNA from 172 mCRPC patients beginning treatment with first-line NHT: abiraterone or enzalutamide. We assessed the impact of germline DNA repair gene mutation status on ≥50% and ≥90% PSA response rates, PSA progression-free survival (PSA-PFS), clinical/radiologic progression-free survival (PFS), and overall survival (OS). Outcomes were adjusted using propensity score-weighted multivariable Cox regression analyses. Results: Among 172 mCRPC patients, germline mutations (in any DNA repair gene) were found in 12.8% (22/172) of men, and germline BRCA/ATM mutations were found in 5.2% (9/172) of men. In unadjusted analyses, outcomes to first-line NHT were better in men with germline BRCA/ATM mutations (vs. no mutations) with respect to ≥90% PSA responses (78% vs. 28%, P = 0.004), PSA-PFS (HR 0.47, P = 0.061), PFS (HR 0.50, P = 0.090) and OS (HR 0.28, P = 0.059). In propensity score-weighted multivariable analyses, outcomes remained superior in men with germline BRCA/ATM mutations with respect to PSA-PFS (HR 0.48, 95%CI 0.25–0.92, P = 0.027), PFS (HR 0.52, 95%CI 0.28–0.98, P = 0.044) and OS (HR 0.34, 95%CI 0.12–0.99, P = 0.048), but this was not true for men with non- BRCA/ATM germline mutations (all endpoints, P > 0.10). Conclusions: Outcomes to first line NHT appeared better in mCRPC patients harboring germline BRCA/ATM mutations (vs. no mutations), but not for patients with other non- BRCA/ATM germline mutations. These results support the hypothesis that AR may promote DNA repair, and that inhibiting AR in the context of homologous recombination deficiency may lead to synthetic lethality.

Outcomes in patients (Pts) with advanced prostate cancer and inactivating germline mutations in BRCA2 or ATM.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Steven Yip ◽  
Daniel Khalaf ◽  
Werner J. Struss ◽  
Katherine Sunderland ◽  
Gillian Vandekerkhove ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Median Time ◽  
Advanced Prostate Cancer ◽  
Germline Mutations ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Available N ◽  
Atm Gene

242 Background: Germline mutations in homologous recombination repair (HRR) genes, including BRCA2, are present in 6-12% of pts with metastatic castration-resistant prostate cancer (mCRPC). BRCA2 germline mutations are associated with high-grade and poor-prognosis localized disease, while outcomes in pts with advanced prostate cancer continue to be defined. Methods: Germline DNA from 536 consecutive mCRPC pts in our liquid biopsy program were screened for BRCA2 and ATM gene mutations using targeted sequencing. Kaplan-Meier curves were used to estimate the median time from androgen deprivation therapy (ADT) initiation to mCRPC, progression free survival (PFS) on first-line androgen receptor (AR) targeted therapy, and overall survival (OS). Outcomes in BRCA2 or ATM germline mutation carriers and a subset of the total sample of HRR wild-type (WT) pts, who had clinical data available (n = 113), were compared using the log-rank test. Results: 26/536 (4.9%) of pts had germline BRCA2 (n = 22) or ATM mutations (n = 4). After ADT initiation, HRR mutated pts progressed to mCRPC with a median time of 13.4 mo compared to 19.0 mo in WT pts (HR = 1.6, [95% CI 1.0-2.5], p = 0.03). HRR mutated pts had a median PFS on first-line AR-targeted therapy in the mCRPC setting of 3.3 mo versus 7.9 mo in WT pts (HR = 2.2, [95% CI 1.3-3.5], p = 0.002). OS for HRR mutated pts from the time of ADT was 57.7 mo in contrast to 104.9 mo in WT pts (HR = 1.8, [95% CI 1.0-3.4], p = 0.07). OS from time of CRPC was 29.7 mo in HRR mutated pts versus 50.3 mo in WT pts (1.6, [95% CI 0.8-2.9], p = 0.16). Conclusions: Germline HRR mutated pts perform poorly with shorter PFS on first-line AR-targeted therapy and time to mCRPC, in contrast to WT pts. These findings support the hypothesis that BRCA2 and ATM gene mutated pts have poor outcomes with current AR-targeted treatments and should be evaluated for alternate regimens.

PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer

2019 ◽  
Vol 37 (6) ◽  
pp. 490-503 ◽  
Author(s):  
Elena Castro ◽  
Nuria Romero-Laorden ◽  
Angela del Pozo ◽  
Rebeca Lozano ◽  
Ana Medina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cohort Study ◽  
Systemic Therapy ◽  
Significant Proportion ◽  
Germline Mutations ◽  
First Line ◽  
Treatment Type ◽  
Brca2 Mutations ◽  
Brca1 Brca2 ◽  
The Impact

Purpose Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes. Patients and Methods Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes. The primary aim was to assess the impact of ATM/BRCA1/BRCA2/ PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. Secondary aims included the association of gDDR subgroups with response outcomes for mCRPC treatments. Combined progression-free survival from the first systemic therapy (PFS) until progression on the second systemic therapy (PFS2) was also explored. Results We identified 68 carriers (16.2%) of 419 eligible patients, including 14 with BRCA2, eight with ATM, four with BRCA1, and none with PALB2 mutations. The study did not reach its primary end point, because the difference in CSS between ATM/BRCA1/BRCA2/PALB2 carriers and noncarriers was not statistically significant (23.3 v 33.2 months; P = .264). CSS was halved in germline BRCA2 (g BRCA2) carriers (17.4 v 33.2 months; P = .027), and g BRCA2 mutations were identified as an independent prognostic factor for CCS (hazard ratio [HR], 2.11; P = .033). Significant interactions between g BRCA2 status and treatment type (androgen signaling inhibitor v taxane therapy) were observed (CSS adjusted P = .014; PFS2 adjusted P = .005). CSS (24.0 v 17.0 months) and PFS2 (18.9 v 8.6 months) were greater in g BRCA2 carriers treated in first line with abiraterone or enzalutamide compared with taxanes. Clinical outcomes did not differ by treatment type in noncarriers. Conclusion g BRCA2 mutations have a deleterious impact on mCRPC outcomes that may be affected by the first line of treatment used. Determination of g BRCA2 status may be of assistance for the selection of the initial treatment in mCRPC. Nonetheless, confirmatory studies are required before these results can support a change in clinical practice.

The impact of time to metastasis on survival in treatment-naïve prostate cancer patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 212-212
Author(s):  
Shusuke Akamatsu ◽  
Kenny Lynch ◽  
Peter Black ◽  
Martin Gleave ◽  
Larry Goldenberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Median Time ◽  
De Novo ◽  
Patient Characteristics ◽  
Initial Diagnosis ◽  
Significant Difference ◽  
Treatment Naïve ◽  
The Impact

212 Background: With the emergence of novel therapies, the treatment of advanced prostate cancer has evolved. However, patients eventually succumb to their metastatic disease. Nonetheless, little is known about the impact of time to metastasis on survival. To further expand on this, we separated metastatic prostate cancer patients into three groups according to the timing of metastasis and analyzed their survival. Methods: From 2008 to 2013, 157 CRPC patients were identified in our database. Of those, 92 with metastasis and sufficient data were analysed. The patients were classified into three groups according to the timing of metastasis. There were 35 de novo –M (metastasis within three months of initial diagnosis), 26 CSPC-M (initially metastasis free, metastasis found more than 6 months prior to CRPC), and 31 CRPC-M (metastasis found within 6 months of becoming CRPC, or after becoming CRPC). Patient characteristics were analyzed, and survival was calculated. Results: Median follow up were 2.2, 9.6, and 11.8 years for de novo-M, CSPC-M, and CRPC-M. 85 and 84 % in the CSPC-M and CRPC-M respectively had local therapies by surgery and/or radiation. The types of local therapies were similar between the groups. Mean time to PSA recurrence after intial therapy were 3.5 and 2.2 years for CSPC-M and CRPC-M, and median time to metastasis were 4.4 and 11.4 years respectively. Treatments after CRPC included Abiraterone, Enzalutamide, and Docetaxel, and the use of these agents were similar between the groups. Median time to CRPC were 1.4, 6.2, and 8.6 years, and median overall survival after diagnosis were 3.7, 12.3, and 15.8 years for de novo-M, CSPC-M, and CRPC-M. Conclusions: The overall survival and time to CRPC were significantly shorter in de novo-M. Although there was a marked difference in time to metastasis between CSPC-M and CRPC-M, there was no statistically significant difference in overall survival. Either treated with hormone therapy before or after emergence of metastasis, survival of more than 10 years after initial diagnosis is possible.

scholarly journals Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Teppei Okamoto ◽  
Daisuke Noro ◽  
Shingo Hatakeyama ◽  
Shintaro Narita ◽  
Koji Mitsuzuka ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Abiraterone Acetate ◽  
Tumor Burden ◽  
Hazard Ratio ◽  
Historical Cohort ◽  
High Tumor Burden ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
The Impact

Abstract Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). Results We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. Conclusion Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

scholarly journals Risk-adapted approach to prostate cancer screening

2018 ◽  
Vol 14 (2) ◽  
pp. 109-121 ◽  
Author(s):  
A. A. Kirichek ◽  
L. N. Lyubchenko ◽  
V. B. Matveev
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Germline Mutation ◽  
Prostate Cancer Screening ◽  
Germline Mutations ◽  
Polygenic Inheritance ◽  
Psa Screening ◽  
Psa Testing ◽  
Mutation Carriers ◽  
Brca1 Brca2

Mass prostatic specific antigen (PSA) testing (population-based PSA screening) has remained controversial, nevertheless there are men cohorts likely to benefit from PSA screening. Heritable factors contribute to 60 % risk for developing familial prostate cancer. Despite the fact that its clinical application is challenging due to polygenic inheritance, advances in new generation sequencing technologies permit identifying highly penetrant germline mutations in genes BRCA1, BRCA2, CHEK2, HOXB13 and MMR associated with tremendous increase in risk of developing the prostate cancer. Several germline mutations are associated with clinically aggressiveness of disease and shortened survival. Targeted screening that is based on family history and genomic aberrations should be the next step towards the precision medicine. Men at elevated risk should been performed for early detection are those with familiar history of prostate cancer, or BRCA1, BRCA2, CHEK2, HOXB13 and MMR pathogenic germline mutation carriers, or first line relatives diagnosed with certain types of cancer. Systematic PSA testing in 1–2 years among germline mutation carriers men beginning at age 45 years would contribute to increase in early detection of localized prostate cancer resulting in more chance of curative treatment and improve survival rates

Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 39-39
Author(s):  
Matthew D Tucker ◽  
Andrew Lachlan Schmidt ◽  
Chih-Yuan Hsu ◽  
Yu Shyr ◽  
Andrew J. Armstrong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mortality Rate ◽  
Propensity Score ◽  
Viral Entry ◽  
Primary Diagnosis ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Retrospective Nature ◽  
Ecog Ps ◽  
The Impact

39 Background: The presence of progressing cancer, male sex and advanced age have been shown to increase the severity of coronavirus disease 2019 (COVID-19). Given that the androgen regulated gene TMPRSS2 has been implicated in SARS-CoV-2 viral entry, we hypothesized that ADT may improve COVID-19 outcomes. This analysis evaluated clinical outcomes of pts with PCa with concurrent SARS-CoV-2 infection and investigated the impact of ADT on occurrence of severe-COVID-19 and mortality. Methods: Data was obtained via the COVID-19 and Cancer Consortium (CCC19), a multicenter registry including >120 cancer centers with de-identified data from pts with COVID-19 and cancer. Men with confirmed SARS-CoV-2 infection and a primary diagnosis of prostate cancer were included: data cutoff of July 31, 2020. The primary endpoint was the development of severe-COVID-19 (death, ICU admission, or mechanical ventilation) among pts on ADT vs. those not on ADT at time of COVID-19 infection. Secondary endpoints included 30-day mortality based on ADT use. Mortality and development of severe-COVID-19 were assessed in Pts grouped by therapy: 1st generation androgen receptor inhibitor (ARI-1), 2nd generation ARI (darolutamide, enzalutamide, apalutamide, ARI-2), abiraterone/prednisone, and chemotherapy. Propensity score matching was utilized. Logistic regression was utilized to adjust for age, ECOG PS, comorbidities, and race. Results: 589 pts were included; median follow-up was 42 days (IQR 25-90) and 62% (363/589) were hospitalized. Severe-COVID-19 developed in 28% of pts and the all-cause 30-day mortality rate was 19%. There was no significant difference in the development of severe-COVID-19 or 30-day mortality between Pts on ADT vs not on ADT, whether using descriptive statistics with the entire population or using the propensity score matched population (Table). Among the descriptive population, the numerical rates of severe-COVID-19 and mortality were lowest in Pts receiving ARI-2, but sample size was low. Conclusions: The overall 30-day mortality rate and percentage developing severe-COVID-19 were high. There was no statistical difference in the development of severe-COVID-19 or mortality based on receipt of ADT; however, this analysis is limited by the retrospective nature and small N after propensity-matching. [Table: see text]

Obesity is a predictor in prostate cancer patients receiving prostatectomy after neoadjuvant hormonal therapy

2019 ◽  
Vol 106 (2) ◽  
pp. 133-138
Author(s):  
Lijiang Sun ◽  
Ting Xu ◽  
Xiaoliang Yuan ◽  
Feng Liu ◽  
Fengju Guan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Roc Curve ◽  
Normal Weight ◽  
Castration Resistance ◽  
Free Survival ◽  
Positive Margins ◽  
Neoadjuvant Hormonal Therapy ◽  
Pathologic Features ◽  
Significant Difference

Objective: This study aimed to investigate the relationship between obesity and pathologic features and biochemical recurrence in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP) after neoadjuvant hormonal therapy (NHT). Methods: A total of 422 consecutive patients with clinically localized PCa who received NHT before RP were retrospectively analyzed. Unconditional multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) regarding probability. A receiver operating characteristic (ROC) curve was used to assess the efficacy of the predictive variables. Castration resistance free survival curves were obtained using the Kaplan-Meier method, and were compared using the log-rank test. Results: Being overweight was associated with an increased risk of positive margins (OR 2.281; 95% CI 1.292–4.028) after adjusting for potential confounders. The area under the ROC curve for overweight patients was larger than that for patients in the normal weight range. There was no significant difference between the overweight and normal weight groups regarding castration resistance free survival. Conclusions: Being overweight was associated with positive margins in patients with PCa undergoing RP after NHT.

scholarly journals Efficacy and safety of combined androgen blockade with antiandrogen for advanced prostate cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Y. Yang ◽  
R. Chen ◽  
T. Sun ◽  
L. Zhao ◽  
F. Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
First Line ◽  
Combined Androgen Blockade ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Grade 3 ◽  
Androgen Blockade

Background Combined androgen blockade (cab) is a promising treatment modality for prostate cancer (pca). In the present meta-analysis, we compared the efficacy and safety of first-line cab using an antiandrogen (aa) with castration monotherapy in patients with advanced pca.Methods PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (rcts) published through 12 December 2016. Hazard ratios (hrs) with 95% confidence intervals (cis) were determined for primary outcomes: overall survival (os) and progression-free survival (pfs). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal aa (nsaa) compared with a steroidal aa (saa).Results Compared with castration monotherapy, cab using an aa was associated with significantly improved os (n = 14; hr: 0.90; 95% ci: 0.84 to 0.97; p = 0.003) and pfs (n = 13; hr: 0.89; 95% ci: 0.80 to 1.00; p = 0.04). No significant difference in os (p = 0.71) and pfs (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, cab using a nsaa was associated with significantly improved os (hr: 0.88; 95% ci: 0.82 to 0.95; p = 0.0009) and pfs (hr: 0.85; 95% ci: 0.73 to 0.98; p = 0.007)—a result that was not achieved with cab using a saa. The safety profiles of cab and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with cab using an aa.Conclusions Compared with castration monotherapy, first-line cab therapy with an aa, especially a nsaa, resulted in significantly improved os and pfs, and had an acceptable safety profile in patients with advanced pca.

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