Proliferation index and survival in men with prostate cancer starting long-term androgen deprivation therapy in the STAMPEDE clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5076-5076
Author(s):  
Larissa Mendes ◽  
Christopher D. Brawley ◽  
Emily Grist ◽  
Adnan Ali ◽  
Sara Santos Vidal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Regression Models ◽  
Advanced Prostate Cancer ◽  
Progression Free Survival ◽  
Proliferation Index ◽  
Metastatic Progression ◽  
Treatment Intensification ◽  
Free Survival ◽  
Secondary Outcomes

5076 Background: Treatment intensification with docetaxel or abiraterone improved survival for advanced prostate cancer starting androgen deprivation therapy (ADT) in the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE, NCT00268476) trial. However, survival and time-to-progression is highly variable on ADT, introducing the risk of unnecessary toxicity from additional treatments for some patients. Here we test the prognostic association of proliferation index using Ki67 scores in the control arm of the STAMPEDE population of high-risk localised (M0) and metastatic (M1) prostate cancer. Methods: Pre-ADT diagnostic needle biopsies were obtained from 517 men randomized in STAMPEDE arm A between 2006 and 2015. These were assessed for proliferation using an analytically optimised Ki67 immunohistochemistry assay. Ki67 was tested for associations with baseline clinico-pathological variables (Grade group, pre-ADT serum PSA and imaging metastatic burden) in univariable linear-regression models, and for associations with survival outcomes in multivariable Cox-regression models adjusted for these and additional confounding variables. Primary outcome measure was overall survival, secondary outcomes were prostate cancer-specific, failure-free, progression-free and metastatic progression-free survival. Results: Ki67 was available for 475 patients who received ADT only for at least 2 years ± radiotherapy. Of 202 M0, 74 were node positive. Of 273 M1, 116, 127 and 30 were respectively low, high and unknown radiological M1 volume. Ki67 score associated with higher Gleason (p=7.15x10-11) and presence of extra-pelvic metastases (p=1.41x10-8). Increasing Ki67 scores showed a strong linear association with poorer overall survival, with an estimated 2% increase in the hazard of death per percentage increase in the score (adjusted HR=1.02, 95% CI 1.01-1.02; p=1.04x10-5). There was also strong evidence that Ki67 associated positively with all secondary outcomes, including prostate cancer-specific survival (adjusted p=5.50x10-6) and metastatic progression-free survival (adjusted p=3.50x10-9). Conclusions: Ki67 immuno-score is strongly prognostic in clinically advanced prostate cancer independent of Gleason score and the other clinicopathological variables tested in this study. Ki67 is a clinically scalable assay that could improve selection for treatment intensification and provide a tool for screening patients most likely to benefit from further molecular investigation.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

The effect of statins on overall survival and progression-free survival in veterans with prostate cancer: A retrospective single-center experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 169-169
Author(s):  
Brian Warnecke ◽  
Raissa Lakene Djoufack Djoumessi ◽  
Juan Garza ◽  
Michael Mader ◽  
Shreya Chaudhary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
The United States ◽  
Inverse Association ◽  
Free Survival ◽  
End Point ◽  
Anti Cancer ◽  
Statin Use

169 Background: Prostate cancer is the most common cancer in men in the United States. Death in prostate cancer patients is often related to other medical conditions and not prostate cancer itself. Hence, it is important to optimize other co-morbidities, such as hyperlipidemia, hypertension, and cardiovascular diseases in these patients. However, there are numerous studies portraying the ability of statins to increase progression free survival and overall survival of prostate cancer. This has led to significant interest of statins having anti-cancer properties and ultimately improving long term outcomes. Methods: This is a retrospective observational study with chart review of 1,011 patients diagnosed with prostate cancer from 1995 to 2010 in a VA Hospital in San Antonio, Texas. Variables included age at diagnosis, statin use, type of statin (1st, 2nd, or 3rd generation), dose of statin (4 dosage levels), length of statin use, time followed in months (from diagnosis to death or end of study period), death, cause of death, and time to first progressive disease. Progressive disease was defined using PSWG2 guidelines which is PSA increase > / = 25% and at least 2ng/dl above the nadir. The Cox proportional hazards regression model was used to estimate the hazard function, with age, co-morbities and other cancers used as a covariate. End points were death by prostate cancer (56), death by any cancer (140), and death by all causes (484). We also looked at the effects of statins on progression free survival of prostate cancer. Results: The hazard ratio (HR) for use of statins and death by prostate cancer was 0.35, 95% confidence interval (CI): 0.20-0.62 (p = 0.0003), indicating that statin use has a statistically significant positive effect at delaying death by prostate cancer. Death by any cancer was significantly affected by statins with a HR of 0.47, 95% CI: 0.32-0.65 (p < 0.0001). Death by all causes was also affected significantly by statins with a HR of 0.64, 95% CI: 0.53-0.78 (p < 0.0001). Length of statin use, shorter versus longer than 4 years, showed an inverse association with our primary end point with a HR of 0.53, 95% CI: 0.40-0.69 (p < 0.0001). Dose level of statin, fourth level vs 1, 2, and 3, also showed an inverse association with our primary end point with a HR of 0.73, 95% CI: 0.57-0.94 (p = 0.014). Lastly, statin exposure significantly increased progression-free survival with a HR of 0.71, 95% CI: 0.53-0.95 (p < 0.021). Conclusions: It is clear that concomitant statin use increases overall survival in patients with prostate cancer, potentially even having anti-cancer protective effects against mortality. Longer duration of statin use and higher dose levels of statins increase length of overall survival in patients with prostate cancer. As mortality is often not due to prostate cancer, more interestingly, statin exposure is also shown to increase progression-free survival.

Association Between Second Progression-free Survival (PFS2) and Overall Survival in Metastatic Castration-resistant Prostate Cancer

2020 ◽  
Vol 77 (6) ◽  
pp. 763-766 ◽  
Author(s):  
David Lorente ◽  
Elena Castro ◽  
Rebeca Lozano ◽  
Javier Puente ◽  
Nuria Romero-Laorden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant

Association of calcium channel blocker use with prostate cancer aggressiveness, progression-free survival, and overall survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15204-e15204
Author(s):  
Michael Adam Poch ◽  
Diana Mehedint ◽  
Alexandra Curtis ◽  
Kristopher Attwood ◽  
Gregory E. Wilding ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radical Prostatectomy ◽  
Calcium Channel ◽  
Cox Regression ◽  
Medication Use ◽  
Progression Free Survival ◽  
Channel Blockers ◽  
Free Survival ◽  
Cancer Aggressiveness

e15204 Background: Epidemiological studies indicate that the use of calcium channel blockers (CCB) is inversely related to prostate cancer (PCa) incidence. The goal of this study was to examine the association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) or outcome after RP. Methods: Information on medication use, PCa aggressiveness and outcome after RP was retrieved from a prospective database that contains clinical and follow-up (FU) data for all men that have undergone RP at the Department of Urology at Roswell Park Cancer Institute since 1992. The database was queried for anti-hypertensive medication use at the time of diagnosis for all patients with ≥ 1 year FU. Prostate cancer aggressiveness (risk status) and recurrence were defined using NCCN guideline definitions. Cox regression models were performed to compare the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Chi-Square test was used to assess the relationship between CCB use and PCa aggressiveness. Results: 875 men were included in the study. At diagnosis, mean age was 60 (SD ± 7) years and mean serum PSA value was 7.4 (SD ±7.4) ng/ml. 48%, 37%, and 15% of patients had low risk, intermediate risk, or high risk PCa, respectively. 104 (12%) had a history of CCB use. CCB users and non-users were similar by PSA at diagnosis (p=0.97) and tumor aggressiveness (p=0.88). Patients taking CCB were more likely to be older (p=0.023), have a higher BMI (p=0.006) and use additional anti-hypertensive medications (p<0.01). Margin status after radical prostatectomy was similar (p=0.30) between the two groups. Median FU was 42 months. PFS (p=0.82, HR 95% CI: 0.63-1.44) and OS (p=0.72, HR 95% CI: 0.42-3.52) did not differ between the 2 groups. Adjusting for age and PCa aggressiveness did not alter the results observed for PFS (p=0.44, HR 95% CI: 0.62–1.41) and OS (p=0.50, HR 95% CI: 0.04-3.48). PCa aggressiveness was associated with PFS (p=0.001) in the multivariate model. Conclusions: CCB use does not affect PCa aggressiveness at time of diagnosis or improve PFS or OS.

Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Genetic Constitution ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

HSD3B1 and resistance to androgen deprivation therapy in prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 156-156 ◽  
Author(s):  
Jason W.D. Hearn ◽  
Ghada AbuAli ◽  
Cristina Magi-Galluzzi ◽  
Chandana A. Reddy ◽  
Kai-Hsiung Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Distant Metastasis ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Homozygous Variant ◽  
Distant Metastasis Free Survival ◽  
Variant Alleles

156 Background: The somatic mutation HSD3B1(1245A>C) has been mechanistically linked to castration-resistant prostate cancer by encoding a mutant enzyme that augments intratumoral dihydrotestosterone synthesis. Given the HSD3B1(1245C) allele is also frequently found in the germline, we hypothesized men inheriting this variant allele would exhibit resistance to androgen deprivation therapy (ADT), as manifested by worse clinical outcomes. Methods: We used a prospectively maintained prostate cancer registry to identify men treated with ADT for biochemical failure in the post-prostatectomy setting who were without evidence of metastatic disease at the time of ADT initiation. We analyzed progression-free survival, distant metastasis-free survival, and overall survival according to HSD3B1 genotype using Kaplan-Meier methods. Cox proportional hazards regression was performed to evaluate potential gene-dosage effects, with homozygous wild-type men serving as the reference group. Demographic and treatment characteristics were compared across genotypes to assess for possible confounders using Fisher’s exact test and Kruskal-Wallis analysis of variance. Results: Of 118 men genotyped, 37% were homozygous wild-type, 53% were heterozygous, and 10% were homozygous variant. Demographic and treatment characteristics did not differ across groups. Median progression-free survival diminished as a function of the number of variant alleles inherited (6.6 years in homozygous wild-type men, 4.1 years in heterozygotes, and 2.5 years in homozygous variant men; P=0.01). Median distant metastasis-free survival likewise decreased according to the number of variant alleles inherited (9.1 years in homozygous wild-type men, 6.8 years in heterozygotes, and 3.6 years in homozygous variant men; P=0.01). Finally, overall survival also diminished with the number of variant alleles inherited (5-year and 10-year overall survival: 82% and 55% in homozygous wild-type men, 74% and 35% in heterozygotes, and 58% and 0% in homozygous variant men; P=0.006). Conclusions: Inheritance of the variant HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis may predict resistance to ADT for prostate cancer. These findings require validation.

Metastasis-free survival as a predictor of overall survival in non-metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 201-201 ◽  
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
Richard M. Lee-Ying
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Real World ◽  
Advanced Prostate Cancer ◽  
Pearson Correlation ◽  
World Population ◽  
Kendall’S Tau ◽  
Kendall's Tau ◽  
Free Survival ◽  
Castration Resistant

201 Background: Recent trials have shown that apalutamide and enzalutamide can improve metastasis free survival (MFS) in advanced non-metastatic (M0) castrate-resistant prostate cancer (CRPC). MFS is a novel clinical endpoint, demonstrated to be a strong predictor of overall survival (OS) for localized prostate cancer, yet it is unknown if this is also true for M0 CRPC. Our aim was to determine how strongly MFS in M0 CRPC correlates with OS in a real world population. Secondary analyses evaluated whether a rapid PSA-doubling time (PSADT), of ≤10 months, impacts outcomes. Methods: We performed an analysis of patients diagnosed with advanced prostate cancer, followed at the Tom Baker Cancer Centre, in Calgary, Alberta from 2001-2017. Patients were excluded if they did not develop M0 CRPC. MFS and OS were measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes based on PSADT. Correlation between OS and MFS was determined using Pearson Correlation and Kendall’s Tau-B. Results: A total of 1310 patients were identified with advanced prostate cancer, of which 87 developed M0 CRPC. The median age of diagnosis of M0 CRPC was 72 years, with a median Gleason score of 7.0, initial PSA of 10.4, and PSADT of 5.1 months. Only 6 patients were treated with second-generation anti-androgens or chemotherapy. Median MFS and OS after M0 CRPC diagnosis were 44.1 and 83.7 months, respectively. Pearson Correlation between MFS and OS was strong with a coefficient of 0.850 (p < 0.001); with non-parametric Kendall’s Tau, correlation was also strong with a coefficient of 0.632 (p < 0.001). PSADT ≤10 months was identified in 70 patients, and associated with a significantly shorter MFS, compared to a PSADT > 10 months (40.2 vs. 90.4 months; p = 0.001), as well as shorter OS (76.2 vs. 104.3 months; p = 0.008). Conclusions: MFS for M0 CRPC is strongly correlated with OS in a real world population. PSADT of ≤10 months seems to be a useful prognostic tool in estimating MFS and OS in patients with M0 CRPC. MFS was better than expected even in patients with a PSADT of ≤10 months, which may due to our adherence to the biochemical definition of castration-resistant disease, as well as lack of standard imaging intervals in the real world.

Cabazitaxel multiple rechallenge in metastatic castration-resistant prostate cancer: A therapeutic option to increase overall survival?

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 97-97
Author(s):  
Cedric Pobel ◽  
Edouard Auclin ◽  
Diego Teyssonneau ◽  
Brigitte Laguerre ◽  
Mathilde Cancel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]

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