Improved Survival in a Cohort of Trial Participants with Metastatic Castration-resistant Prostate Cancer Demonstrates the Need for Updated Prognostic Nomograms

Omlin, Aurelius; Pezaro, Carmel; Mukherji, Deborah; Mulick, Amy; Sandhu, Shahneen; Bianchini, Diletta; Olmos, David; Ferraldeschi, Roberta; Maier, Gal; Thompson, Emilda; Parker, Chris; Attard, Gerhardt; Bono, Johann S. de

doi:10.1016/j.eururo.2012.12.029

Cited by 86 publications

(44 citation statements)

References 21 publications

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“…These observations underline the importance of improved risk stratification in trials of mCRPC patients, warranting the documentation of the interval between the date of mCRPC diagnosis and trial inclusion. Insufficient risk stratification has recently been described as a possible factor in observed survival differences [16]. For the clinician designing individual therapy regimens for mCRPC patients, the present study supports the notion that aggressive life-prolonging treatment may be delayed for some patients with a good prognosis, characterized by low PSA nadir values during ADT, high PSA doubling times, and normal hemoglobin and alkaline phosphatase levels at mCRPC.…”

Section: Discussionsupporting

confidence: 83%

“Natural course” of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment

Löffeler

Weedon‐Fekjær

Wang-Hansen

et al. 2015

Scandinavian Journal of Urology

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The "natural course" of mCRPC varies without life-prolonging treatment along with PSA nadir during ADT, PSA doubling time, alkaline phosphatase and hemoglobin level at mCRPC diagnosis. 3-year survival or longer is observed in 16.9% of patients. In clinical intervention trials among mCRPC patients, all known prognostic factors should be taken into account during the randomization process and during survival analyses.

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Section: Discussionsupporting

confidence: 83%

“Natural course” of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment

Löffeler

Weedon‐Fekjær

Wang-Hansen

et al. 2015

Scandinavian Journal of Urology

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“…To explore the prevalence of visceral disease in CRPC, we examined our database of clinical trial participants. This population has been described previously [7] and all patients provided consent for data collection in IRB-approved protocols. Patients had regular 12 weekly (or 6 weekly if specified in trial protocols) computed tomography (CT) scans of the thorax, abdomen and pelvis performed for restaging or for investigation of new symptoms.…”

Section: Introductionmentioning

confidence: 99%

Visceral Disease in Castration-resistant Prostate Cancer

et al. 2014

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Metastatic involvement of the viscera in men with advanced castration-resistant prostate cancer (CRPC) has been poorly characterized to date.In 359 CRPC patients treated between June 2003 and December 2011, the frequency of radiologically detected visceral metastases before death was 32%. Of the 92 patients with computed tomography performed within 3 months of death, 49% had visceral metastases. Visceral metastases most commonly involved the liver (20%) and lung (13%). Median survival from diagnosis of visceral disease was 7.1 months (95% CI 5.9 -8.3). Survival was impacted by the degree of bone involvement at detection of visceral disease, varying from 6.1 months in men with >6 bone metastases to 18.2 months in men with no bone metastases (p = 0.001). Heterogeneity was noted in clinical phenotypes and PSA trends at development of visceral metastases. Visceral metastases are now more commonly detected in men with CRPC, likely due to the introduction of novel survival-prolonging treatments.Visceral disease was previously considered uncommon in men with advanced prostate cancer and has been associated with neuroendocrine phenotypes and poor outcome [1]. In recent Phase III post-docetaxel trials, 23-29% of participants had visceral metastases [2][3][4]. Autopsy studies on men who died from prostate cancer suggested a higher prevalence of visceral metastases, up to 66% of selected cases [5], but these metastases did not appear clinically relevant. Subset analyses of patients with visceral disease in the post-docetaxel abiraterone and enzalutamide Phase III trials showed hazard ratios of 0.79 (0.60-1.05) and 0.78 (0.56-1.09) respectively, suggesting these patients may derive benefit from targeting of the androgen receptor (AR) [3,4]. The Phase III clinical trials of sipuleucel-T, radium 223 and abiraterone in chemotherapy-naïve CRPC specifically excluded men with visceral disease. With the introduction of several new survival-prolonging treatments (reviewed in[6]) we hypothesized that more patients will develop visceral involvement, requiring improved recognition and molecular characterization in order to improve individual patient management. To explore the prevalence of visceral disease in CRPC, we examined our database of clinical trial participants. This population has been described previously [7] and all patients provided consent for data collection in IRB-approved protocols. Patients had regular 12 weekly (or 6 weekly if specified in trial protocols) computed tomography (CT) scans of the thorax, abdomen and pelvis performed for restaging or for investigation of new symptoms. Brain CT scans were performed in response to neurological symptoms. Bone metastases were assessed using standard bone scans. These prospectively collected scans were reviewed for evidence of visceral involvement, defined as disease involving liver, lungs, adrenal glands, peritoneum or pleura, brain and dura. Descriptive statistics, Kaplan Meier survival analyses and Cox regressions were performed using SPSS Statistics v20 (IBM). Q...

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“…We also included data and references from peer reviewed organizational guidelines (American Urological Association (AUA), European Association of Urology (EUA), and National Comprehensive Cancer Network (NCCN)). [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] We used www.clinicaltrials.gov to find active clinical trials relevant to the section on "emerging therapies. "…”

Section: Sources and Selection Criteriamentioning

confidence: 99%

Advances in the management of castration resistant prostate cancer

Ritch

Cookson

2016

BMJ

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Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab). Given that docetaxel was the standard first line treatment for metastatic CRPC, the newer oral agents that affect the androgen axis were initially approved in the post-docetaxel setting. However, subsequent randomized trials have led to their approval in the pre-chemotherapy setting as well. Patients with CRPC are clinically heterogeneous, ranging from patients who are asymptomatic and do not have metastases to those with substantial symptoms and both bony and visceral metastases. CRPC is a clinically challenging disease entity, therefore, with a wide array of treatment options and multiple possible sequencing combinations depending on the individual patient. This review will summarize the findings of the randomized trials that led to the approval of the therapies for CRPC. It will also discuss recent guidelines and provide suggestions for sequencing of drugs based on the best available evidence.

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Improved Survival in a Cohort of Trial Participants with Metastatic Castration-resistant Prostate Cancer Demonstrates the Need for Updated Prognostic Nomograms

Cited by 86 publications

References 21 publications

“Natural course” of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment

“Natural course” of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment

Visceral Disease in Castration-resistant Prostate Cancer

Advances in the management of castration resistant prostate cancer

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