Current Clinical Challenges in Prostate Cancer
Current Clinical Challenges in Prostate Cancer
Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease.
Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial.
Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago.
In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field.
Prostate cancer is a highly heterogeneous disease, often with a long natural history. Nearly 240,000 men in the United States are newly diagnosed with prostate cancer annually, and more than 90% of these patients have local disease at diagnosis. Though statistics are variable, some autopsy reports indicate that the majority of men over age 50 harbor detectable prostate cancer after careful microscopic examination of the prostate. Although this data would suggest that prostate cancer follows an indolent course, it results in the death of nearly 30,000 American annually and approximately 2.7% of men in the United States are estimated to die from prostate cancer in their lifetime. The incidence/mortality ratio for prostate cancer is approximately 8, making it distinct from any other major cancer (Table 1). This perplexing series of dichotomous facts were eloquently summarized by the late the late Dr. Whitmore, "when a cure is possible is it necessary? And when it's necessary is it possible?" Reconciling this data involves stratifying patients by their risk of progression and offering appropriate therapy (or non-therapy) based on the risk of disease, comorbidities and life expectancy. After cancer progresses, additional challenges are encountered. Only radiation and surgery have been shown to reliably cure patients and when these modalities fail, additional management problems ensue within each disease state that follows. Much progress has been made in metastatic castrate-resistant disease of late and this progress is highlighted herein. This summary is an introduction to many of the pertinent clinical challenges that face clinicians in treating and managing this complex and multi-faceted disease.
Abstract and Introduction
Abstract
Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease.
Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial.
Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago.
In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field.
Introduction
Prostate cancer is a highly heterogeneous disease, often with a long natural history. Nearly 240,000 men in the United States are newly diagnosed with prostate cancer annually, and more than 90% of these patients have local disease at diagnosis. Though statistics are variable, some autopsy reports indicate that the majority of men over age 50 harbor detectable prostate cancer after careful microscopic examination of the prostate. Although this data would suggest that prostate cancer follows an indolent course, it results in the death of nearly 30,000 American annually and approximately 2.7% of men in the United States are estimated to die from prostate cancer in their lifetime. The incidence/mortality ratio for prostate cancer is approximately 8, making it distinct from any other major cancer (Table 1). This perplexing series of dichotomous facts were eloquently summarized by the late the late Dr. Whitmore, "when a cure is possible is it necessary? And when it's necessary is it possible?" Reconciling this data involves stratifying patients by their risk of progression and offering appropriate therapy (or non-therapy) based on the risk of disease, comorbidities and life expectancy. After cancer progresses, additional challenges are encountered. Only radiation and surgery have been shown to reliably cure patients and when these modalities fail, additional management problems ensue within each disease state that follows. Much progress has been made in metastatic castrate-resistant disease of late and this progress is highlighted herein. This summary is an introduction to many of the pertinent clinical challenges that face clinicians in treating and managing this complex and multi-faceted disease.
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