scholarly journals Contribution of Inherited DNA-Repair Gene Mutations to Hormone-Sensitive and Castrate-Resistant Metastatic Prostate Cancer and Implications for Clinical Outcome

2019 ◽  
pp. 1-12
Author(s):  
Siddhartha Yadav ◽  
Steven N. Hart ◽  
Chunling Hu ◽  
David Hillman ◽  
Kun Y. Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Gene Mutations ◽  
Germline Mutations ◽  
Hazard Ratio ◽  
Poor Overall Survival ◽  
Mutation Status ◽  
Hormone Sensitive ◽  
Castrate Resistant

PURPOSE To compare the prevalence of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) and assess the impact of mutations on progression to castration resistance and overall survival. METHODS Targeted sequencing of germline DNA from 704 men (221 at the time of mHSPC and 483 at the time of mCRPC) enrolled in two advanced prostate cancer registries at Mayo Clinic between 2003 and 2013 was performed for 21 predisposition genes. Frequencies of pathogenic mutations were compared in patients and reference controls to identify genes enriched in metastatic prostate cancer. Multivariable Cox proportional hazards regression was used to identify predictors of progression to mCRPC and overall survival. RESULTS Sixty-eight germline mutations in 12 genes were identified in 66 men (9.4%). Mutations in ATM, BRCA2, CHEK2, FANCM, and TP53 were significantly enriched (odds ratio greater than 2.0) in the metastatic cohorts compared with reference controls. The frequency of germline mutations was similar for patients with mHSPC and mCRPC (11.8% v 8.3%; P = .16). The median time to progression from mHSPC to mCRPC was 23.1 and 32.5 months for patients with and without mutations, respectively ( P = .96). Although older age at diagnosis, Gleason score greater than 7, elevated alkaline phosphatase level, and high volume of disease were associated with shorter duration of progression to mCRPC and poor overall survival, mutation status was not (progression to mCRPC hazard ratio, 0.81; 95% CI, 0.61 to 1.09; P = .17; overall survival hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P = .98). CONCLUSION Similarly elevated rates of germline predisposition gene mutations in mHSPC and mCRPC suggest that germline genetic testing may help to guide medical management for all patients with advanced metastatic prostate cancer. Mutation status was not associated with shorter progression to mCRPC or poor overall survival.

Patterns of response to androgen deprivation therapy in younger patients with locally advanced or metastatic prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 324-324
Author(s):  
Matthew Keating ◽  
Lisa Giscombe ◽  
Andre Desouza ◽  
Shiva Kumar Reddy Mukkamalla ◽  
Ritesh Rathore
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Standards Of Care ◽  
National Cancer Database ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

324 Background: Androgen deprivation therapy (ADT) remains a standard of care in the treatment of locally advanced prostate cancer. But thanks to a few key trials (STAMPEDE, CHAARTED, and LATITUDE) reported within the past three years, docetaxel and abiraterone now have roles in extending overall survival in a patient population traditionally treated with ADT alone. These treatments when combined with ADT have been shown to extend overall survival in metastatic hormone-sensitive prostate cancer patients. The role of ADT in relation to other therapies continues to evolve rapidly. We intend to revisit ADT’s longstanding role in prostate cancer treatment using a national cancer database. Our aim is to look beyond traditional standards of care to identify patients more likely to have overall survival benefit from ADT. Are there any subgroups of patients with intermediate or high risk disease that have improved survival outcomes with androgen deprivation therapy, besides patients with localized disease that underwent radiation? Could there be other variables besides PSA and localization of the prostate cancer that should be considered when identifying ADT treatment candidates, or identifying survival trends in these groups? Methods: We are currently analyzing variables present in the National Cancer Database to retrospectively identify predictive factors for overall survival and progression to metastatic castrate resistant prostate cancer in locally advanced prostate cancers treated with ADT. We will evaluate time-to-death from the initiation of ADT and from the diagnosis of metastatic castrate resistant prostate cancer. The following variables in localized, locally advanced, and metastatic prostate cancer will be analyzed with Statistical Analysis Software: age, locally advanced, site-specific metastasis (M1a, M1b, M1c), Gleason score, local treatment (radical prostatectomy or radiation), stage (T, N, and M), prostate lobe (one vs. both; T2a/b vs. T2c), chemotherapy (date, time from M1 stage), comorbidity score, ethnicity, facility type, insurance, and risk groups (low/intermediate/high as per NCCN guidelines).

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 <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.

Docetaxel in older patients for metastatic prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 187-187 ◽  
Author(s):  
Frances May Mark ◽  
Adam Pollard ◽  
Alastair H Thomson
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Practice ◽  
Metastatic Prostate Cancer ◽  
Age Groups ◽  
Response Rates ◽  
Routine Clinical Practice ◽  
Age Group ◽  
Psa Response ◽  
Castrate Resistant

187 Background: Docetaxel use has led to a significant prolongation in overall survival in metastatic prostate cancer (MPC). There is however limited information on treatment tolerance and outcomes in patients 80 years old and over in routine clinical practice. With the ever aging population it is becoming more important to assess outcomes in this age group. Methods: Patients diagnosed with MPC and treated with docetaxel from 2006 to 2016 were identified and their records retrospectively reviewed via electronic clinical and prescribing systems in a single centre in the UK. Data was assessed for prostate specific antigen (PSA) response, number of cycles and dosing of docetaxel and castrate resistant overall survival (OS). Results: 209 consecutive patients with MPC receiving docetaxel were reviewed. Three patient groups were identified; younger than 75 years old (n = 150, 37 early (as part of initial therapy) docetaxel), 75-79 years (n = 40, 2 early docetaxel) and 80 years or over (n = 19, no early docetaxel). When comparing mean OS excluding early docetaxel treatment, respective mean survival times for each of the three age groups, younger to older were 1001, 1045 and 1294 days, with between class difference being insignificant. The PSA response rates to docetaxel excluding first line use were compared between the age groups and did not show a significant difference at 39% in the youngest group, 38% in the intermediate age group and 42% for the oldest patients. There was a trend that the older the patient, the more likely docetaxel was the final systemic treatment given at 42% (80 years or over), 32% (75-79 years) and 23% (younger than 75 years). The 80 years or over group received fewer docetaxel cycles (3.8, p = 0.006) and less dose per course (226mg/m2, p = 0.004) than the group less than 75 years (5.8 cycles, 409mg/m2) and 75-79 years (5.1 cycles, 341mg/m2). Conclusions: In this group of patients, in routine clinical practice, the 80 years and over age group received fewer cycles of docetaxel in MPC and less dose per course, but nevertheless achieved similar PSA response rates and castrate resistant OS. Given these results, docetaxel should be considered as a treatment option in suitable patients of 80 years and over.

scholarly journals Enzalutamide in Metastatic Prostate Cancer Before Chemotherapy

2021 ◽  
pp. 101-106
Author(s):  
Joseph Zabell
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

This chapter summarizes the findings of the landmark PREVAIL trial conducted in men with castrate-resistant prostate cancer who had received prior chemotherapy comparing enzalutamide to placebo. It demonstrated improved overall survival, radiographic progression-free survival, and time to cytotoxic chemotherapy.

Abiraterone and Increased Survival in Metastatic Prostate Cancer

2021 ◽  
pp. 95-100
Author(s):  
Joseph Zabell
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Adverse Effects ◽  
Metastatic Prostate Cancer ◽  
Prior Chemotherapy ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

This chapter summarizes the findings of a landmark trial conducted in men with castrate-resistant prostate cancer who had received prior chemotherapy comparing abiraterone to placebo. It demonstrated improved progression-free and overall survival. It was relatively well tolerated, with most adverse effects related to mineralocorticoid excess.

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.

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