scholarly journals Prognostic Impact of Sarcopenia in Patients with Metastatic Hormone-Sensitive Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6345
Author(s):  
Ji Hyun Lee ◽  
Byul A Jee ◽  
Jae-Hun Kim ◽  
Hoyoung Bae ◽  
Jae Hoon Chung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Rank Test ◽  
Prognostic Impact ◽  
Skeletal Muscle Index ◽  
Free Survival ◽  
Psa Progression ◽  
Hormone Sensitive

The clinical value of sarcopenia has not been determined yet in metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively evaluated data of 70 consecutive patients with mHSPC receiving treatment with either early docetaxel (n = 42) or abiraterone acetate (n = 28) between July 2018 and April 2021. Skeletal muscle index was calculated from cross-sectional areas of skeletal muscle on baseline computed tomography (CT), defining sarcopenia as a skeletal muscle index of ≤52.4 cm2/m2. Failure-free survival (FFS), radiographic progression-free survival, and time to prostate-specific antigen (PSA) progression were estimated using the Kaplan–Meier method, and differences in survival probability were compared using the log-rank test. Cox proportional hazards regression analysis was conducted to identify the predictors of clinical outcomes. Patients with sarcopenia (n = 47) had shorter FFS than those without sarcopenia (n = 23) (median, 20.1 months vs. not reached; log-rank p < 0.001). Sarcopenia was independently associated with shorter FFS (hazard ratio (HR), 6.69; 95% confidence interval (CI), 1.57–28.49; p = 0.010) and time to PSA progression (HR, 12.91; 95% CI, 1.08–153.85; p = 0.043). In conclusion, sarcopenia is an independent prognostic factor for poor FFS and time to PSA progression in patients with mHSPC who receive early docetaxel or abiraterone acetate treatment.

Prognostic impact of sarcopenia in patients with metastatic hormone-sensitive prostate cancer

2020 ◽  
Vol 50 (8) ◽  
pp. 933-939
Author(s):  
Takashi Ikeda ◽  
Hiroki Ishihara ◽  
Junpei Iizuka ◽  
Yasunobu Hashimoto ◽  
Kazuhiko Yoshida ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Hazard Ratio ◽  
Rank Test ◽  
Prognostic Impact ◽  
Castration Resistance ◽  
Consensus Definition ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Hormone Sensitive

Abstract Background Cancer cachexia is associated with a poor prognosis. This study aimed to investigate the association between sarcopenia and survival in patients with metastatic hormone-sensitive prostate cancer. Methods We retrospectively evaluated 197 patients diagnosed with metastatic hormone-sensitive prostate cancer in our department and its affiliated institution between January 2008 and December 2015. Sarcopenia was diagnosed according to the sex-specific consensus definition. Castration-resistance prostate cancer-free survival, cancer-specific survival and overall survival from the metastatic hormone-sensitive prostate cancer diagnoses were calculated using the Kaplan–Meier method and compared using the log-rank test. Risk factors affecting the survival outcomes were analyzed using the Cox proportional regression analysis. Results In total, 163 patients (82.7%) had sarcopenia. Cancer-specific survival and overall survival were significantly shorter in sarcopenic patients than in non-sarcopenic patients (median cancer-specific survival: 77.0 months vs. not reached, P = 0.0099; overall survival: 72.0 months vs. not reached, P = 0.0465), whereas castration-resistance prostate cancer-free survival did not significantly differ between the groups (P = 0.6063). Multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.18, P = 0.0451), together with the Gleason score (hazard ratio: 1.87, P = 0.0272) and LATITUDE risk classification (hazard ratio: 2.73, P = 0.0008). Moreover, the prognostic association of sarcopenia was remarkable in patients aged &lt;73.0 years (cancer-specific survival: 82.0 months vs. not reached, P = 0.0027; overall survival: 72.0 months vs. not reached, P = 0.0078 in sarcopenic vs. non-sarcopenic patients), whereas the association was not significant in patients aged ≥73.0 years (cancer-specific survival: 76.0 and 75.0 months, respectively, P = 0.7879; overall survival: 67.0 and 52.0 months, respectively, P = 0.7263). Conclusion Sarcopenia was an independent risk factor of cancer-specific survival in patients with metastatic hormone-sensitive prostate cancer, especially in younger patients.

scholarly journals Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment

2018 ◽  
Vol 36 (25) ◽  
pp. 2639-2646 ◽  
Author(s):  
Gerhardt Attard ◽  
Michael Borre ◽  
Howard Gurney ◽  
Yohann Loriot ◽  
Corina Andresen-Daniil ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Control Group ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Progression

Purpose Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO ( ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.

Dynamic Changes in Prostate-Specific Antigen After Androgen Deprivation Therapy for Prostate Cancer are Strongly Associated with Biochemical Progression-Free Survival: A Multicenter Retrospective Analysis

2021 ◽  
Author(s):  
Mingqiu Hu ◽  
Yifeng Mao ◽  
Kaizhong Zhang ◽  
Chao Guan ◽  
Aiming Wu
Keyword(s):  
Prostate Cancer ◽  
Survival Curve ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Prognostic Indicators ◽  
Rank Test ◽  
Dynamic Changes ◽  
Free Survival ◽  
Biochemical Progression

Abstract Objectives: The risk factors for prostate cancer to progress to castration-resistant prostate cancer after androgen deprivation treatment (ADT) are still not to be well defined. We conducted this investigation in an attempt to determine factors that predicted the prognosis in a series of patients with prostate cancer after ADT. Methods: We retrospectively analyzed the database of patients treated with androgen deprivation prostate cancer who were hospitalized in the Second Affiliated Hospital of Bengbu Medical College and Maoming People's Hospital from 2015.1.1 to 2020.12.30. PSA dynamic changes, including nadir PSA (nPSA), time to nadir PSA (TTN), were examined regularly. Cox risk proportional regression model was used for univariate and multivariate analysis; Kaplan-Meier survival curve and Log-rank test were used to compare and analyze differences in biochemical progression-free survival (bPFS) between groups. Results: During the follow-up with a median time of 43.5 months, a total of 163 men were included in the study. The median bPFS of the two groups with nPSA lower than 0.2ng/ml and ≥0.2ng/ml were 27.6 months and 13.5, respectively, with significant differences between the groups (Log-rank p<0.001); The median bPFS of the two groups with TTN ≥9 months and less than 9 were 27.8 months and 13.5 months, respectively, with significant differences between the groups (Log rank p<0.001). Conclusions: PSA dynamic changes after androgen deprivation treatment of prostate cancer can be used as prognostic indicators for bPFS. The lower the nadir PSA value and the longer the time to nadir, the longer the bPFS of patients with prostatic cancer after androgen deprivation treatment.

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

scholarly journals Abiraterone versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer.

2021 ◽  
Author(s):  
Takashi Ueda ◽  
Takumi Shiraishi ◽  
Saya Ueda ◽  
Motoharu Ohashi ◽  
Toru Matsugasumi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Progression Free Survival ◽  
Gonadotropin Releasing Hormone ◽  
Free Survival ◽  
Releasing Hormone ◽  
Group A ◽  
Psa Progression ◽  
Hormone Sensitive ◽  
Group B

Abstract ObjectivesTo compare the efficacy of abiraterone with that of bicalutamide in combination with gonadotropin-releasing hormone antagonist treatment for high risk metastatic hormone-sensitive prostate cancer patients.MethodsOne hundred and forty-nine patients with high risk metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone (1000mg/day) plus prednisolone (5mg/day) with gonadotropin-releasing hormone antagonist (degarelix) (group A) and 99 patients were administered bicalutamide (80mg/day) with gonadotropin-releasing hormone antagonist (group B). ResultsPSA- progression-free survival of group A was significantly longer than that of group B. Abiraterone therapy and Gleason score were significant independent factors for PSA-progression-free survival. By propensity score matching, total 56 matched patients were obtained. PSA-PFS (p<0.001) and OS (p=0.0071) of high risk mHNPC patients were significantly longer in abiraterone group of matched patients. Abiraterone therapy and Gleason score were still shown to be significant independent factors for PSA-PFS in matched patients.ConclusionsPSA-progression-free survival and overall survival in patients who were treated with abiraterone in combination with gonadotropin releasing hormone antagonist were significantly better than those of bicalutamide.

Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Bo Zhao ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Brian I. Rini ◽  
Robert Dreicer
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Underlying Mechanism ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.

Interim results from a phase 2 study of olaparib (without ADT) in men with biochemically-recurrent prostate cancer after prostatectomy, with integrated biomarker analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5045-5045 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Hao Wang ◽  
Benjamin A. Teply ◽  
William Kevin Kelly ◽  
Jamie Willms ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adaptive Design ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Parp Inhibition ◽  
Free Survival ◽  
Second Stage ◽  
Biomarker Analysis ◽  
Psa Progression ◽  
Hormone Sensitive

5045 Background: Pts with biochemically-recurrent (BCR) prostate cancer after local therapy with a PSA doubling time (PSADT) of ≤6 mo are likely to develop metastases and death from their disease. We hypothesized that the PARP inhibitor olaparib would be effective as a non-hormonal therapy for biomarker-unselected pts with BCR after prostatectomy, the first study of PARP inhibition in the hormone-sensitive setting. We report pre-specified interim results from the first stage of the trial. Methods: This investigator-initiated multicenter study (NCT03047135) enrolled pts with non-metastatic BCR after prostatectomy, with a PSADT of ≤6 mo. PSA had to be ≥1.0 ng/mL, with T ≥150 ng/dL. Pts received olaparib 300 mg twice daily (without ADT), until a doubling of their PSA or metastatic progression. The primary endpoint was confirmed ≥50% PSA decline (PSA50 response). Secondary endpoints included safety, minor PSA response (1-50% reduction), and PSA progression-free survival. Integrated biomarker analyses included somatic DNA sequencing, RNA expression analysis and IHC for DNA damage markers, using prostatectomy specimens. The study was designed to enroll a biomarker-unselected population using a staged-adaptive design, with up to 50 pts. In the first stage, ≥3 PSA50 responses out of 20 pts were required to proceed to the second stage; otherwise enrichment with biomarker-selected pts would occur. Results: Between 5/2017 and 11/2018, 20 men (median age, 65) enrolled in the first stage, with a median follow-up of 6 (range, 3-16) mo. Median PSADT was 3.1 mo, and 55% had Gleason ≥8 cancers. Seven men (35%) had BRCA2/ATM mutations. Three men (15%) had PSA50 responses (all had BRCA2 muts – 2 had complete PSA responses), and 4 other men (20%) had minor PSA responses. Median PSA progression-free survival was greater in men with vs. without BRCA2/ATM muts (9 vs. 4 mo; P= 0.02). Common toxicities of olaparib included fatigue, nausea, anemia and leukopenia; 2 men required a dose reduction. Conclusions: Olaparib (without ADT) was tolerable and showed activity in hormone-sensitive BCR prostate cancer, especially in men with BRCA2 muts. Second-stage enrolment is ongoing. Clinical trial information: NCT03047135.

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