ASCO, Author Interviews, Cost of Health Care, Prostate Cancer, Surgical Research / 06.06.2016
Radical Prostatectomies: Referral to High Volume Centers Saves Money
MedicalResearch.com Interview with:
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Dr. Sarmad Sadeghi[/caption]
Sarmad Sadeghi MD, MS, PhD
Assistant Professor of Medicine
Norris Comprehensive Cancer Center
University of Southern California
MedicalResearch.com: What is the background for this study?
Dr. Sadeghi: Several years ago analyses of outcomes for radical prostatectomy highlighted the significant impact of surgical experience on the oncological outcome for the patients. In this case experience was measured by the number of radical prostatectomies performed by the surgeon, and oncological outcome was measured by treatment failure rates (rising PSA). Despite this data, the move for redirecting patients to “high volume centers” where more experienced surgeons perform the operation has been sluggish. There was insufficient data on what is involved in referring patients to high volume centers and whether or not such action is cost effective.
In a previous study we demonstrated that for every referral to a high volume center, there would be an average of $1,800 over a follow-up period of 20 years in societal cost savings. The main source of these savings is fewer treatment failures.
The next question was who is a good candidate for referral and whether these savings can offset the referral costs.
Dr. Sarmad Sadeghi[/caption]
Sarmad Sadeghi MD, MS, PhD
Assistant Professor of Medicine
Norris Comprehensive Cancer Center
University of Southern California
MedicalResearch.com: What is the background for this study?
Dr. Sadeghi: Several years ago analyses of outcomes for radical prostatectomy highlighted the significant impact of surgical experience on the oncological outcome for the patients. In this case experience was measured by the number of radical prostatectomies performed by the surgeon, and oncological outcome was measured by treatment failure rates (rising PSA). Despite this data, the move for redirecting patients to “high volume centers” where more experienced surgeons perform the operation has been sluggish. There was insufficient data on what is involved in referring patients to high volume centers and whether or not such action is cost effective.
In a previous study we demonstrated that for every referral to a high volume center, there would be an average of $1,800 over a follow-up period of 20 years in societal cost savings. The main source of these savings is fewer treatment failures.
The next question was who is a good candidate for referral and whether these savings can offset the referral costs.
Dr. Kenneth Iczkowski,[/caption]
Kenneth A. Iczkowski, M.D.
Department of Pathology
Medical College of Wisconsin
Milwaukee, WI 53226
MedicalResearch.com: What is the background for this study?
Dr. Iczkowski: The International Society of Urological Pathology (ISUP) in 2014 proposed use of a new 5-tier grade grouping system to supplement traditional Gleason grading to facilitate prognosis stratification and treatment1. The 5 categories subsume: Gleason 3+3=6, Gleason 3+4=7, Gleason 4+3=7, Gleason 8, and Gleason 9-10.
We desired to determine whether men with a highest Gleason score of 3+5=8 or 5+3=8 in their set of prostate biopsy specimens, would have differing outcomes from those with Gleason 4+4=8. Because Gleason 5 cancer has been demonstrated to have a higher biologic potential than Gleason 4, it was expected that Gleason score 8 pattern with any Gleason 5 pattern would have a worse outcome.
Dr-Aurora-Perez-Cornago[/caption]
Aurora Perez-Cornago, PhD
Cancer Epidemiology Unit
Nuffield Department of Population Health
University of Oxford
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Excessive body size and adiposity have been proposed to influence
several metabolic and hormonal mechanisms that can promote cancer development.
We found that men who have greater adiposity have an elevated risk of
high grade prostate cancer, an aggressive form of the disease, and
prostate cancer death.
Dr. Jonathan Shoag[/caption]
Jonathan Shoag MD
Urology Resident at
Cornell Department of Urology and
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Dr. Jim Hu[/caption]
Dr. Jim C. Hu MD
Ronald Lynch Professor of Urologic Oncology
Professor of Urology
Director, Lefrak Center for Robotic Surgery
Attending Urologist, New York-Presbyterian Hospital (Cornell campus)
MedicalResearch.com: What is the background for this study?
Response: Prostate Specific Antigen (PSA) is a blood test that is used to detect prostate cancers and to follow a cancer’s response to treatment. PSA was widely implemented as a screening tool for prostate cancer in the early 1990s, and became a routine test during an annual physical for men over 40. Doctors started using it because values above a “normal” threshold were associated with a greater risk of prostate cancer. Following the adoption of PSA screening in the early 1990s, there has been a large increase in the number of men diagnosed with cancer, and a decrease of approximately 50% in the rate of prostate cancer death.
The PLCO trial was a large randomized trial designed and funded by the National Cancer Institute (NCI) to determine the effect of PSA screening on death from prostate cancer. The trial found that men randomized/assigned to prostate cancer screening had the same number of prostate cancer deaths as men in the control group of the trial, arguing that PSA screening does not decrease prostate cancer mortality.
This was a major piece of evidence used by the United States Preventative Services Task Force (USPSTF) to form its 2012 recommendation against PSA screening. The argument was that in spite of the other evidence showing a benefit to PSA testing, including US epidemiologic trends, and another large randomized trial showing PSA screening was effective (the ERSPC), we now had good evidence showing no benefit to PSA testing in the US. Since 2012 we have seen dramatic declines in prostate cancer screening in the US as a result.
Dr. Vikas Gulani[/caption]
Dr. Vikas Gulani MD, PhD
Director, MRI, University Hospitals Case Medical Center
Associate Professor, Radiology
CWRU School of Medicine
Cleveland, OH
MedicalResearch.com: What is the background for this study?
Dr. Gulani: For men that have a suspicion for prostate cancer either via the prostate specific antigen (PSA) test or a digital rectal exam, the current standard of care is to perform a transrectal ultrasound (TRUS) guided biopsy to detect cancer. The problem with TRUS biopsy is that most tumors are not visible on ultrasound and hence many significant cancers are missed. At the same time this strategy detects a high number of low risk, indolent cancers, and leads to overtreatment of disease that would be better left untreated.
Diagnostic MRI and MRI-guided biopsy (cognitive, ultrasound-MR fusion, or in-gantry) have been shown to be effective in detecting clinically significant prostate cancer. However, despite these advantages there is reluctance to incorporate MRI into standard practice because it is perceived to be expensive. Our goal was to determine if this presumption is true, and evaluate the cost-effectiveness of the MRI-guided techniques most commonly used.
MedicalResearch.com: What are the main findings?
Dr. Gulani: We found that every MRI strategy we evaluated was cost-effective compared to standard biopsy. Cognitive MRI guided biopsy – where the operator performs an ultrasound biopsy based on knowledge of lesion location from the MRI – was the most cost-effective strategy compared to standard biopsy. In-gantry MRI yielded the highest net health benefits as measured in quality adjusted life years.
Dr. Stephen Freedland[/caption]
Stephen J. Freedland, MD
Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute
Co-Director, Cancer Genetics and Prevention Program
Director, Center for Integrated Research in Cancer and Lifestyle
Professor, Surgery
Warschaw Robertson Law Families Chair in Prostate Cancer
Cedars-Sinai, Los Angeles
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Freedland: PSA is a marker of prostate pathology. While often used to screen for prostate cancer, it is not prostate specific and can be elevated due to inflammation or enlarged prostate or other reasons. Whether it predicts the development of urinary symptoms is not clear. Among men with minimal to no urinary symptoms, we found that the higher the PSA, the greater the risk of future development of urinary symptoms.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Freedland: The readers should know that if a man has an elevated PSA and a negative prostate biopsy, the higher the PSA, the greater the risk of future urinary symptoms. These are men who may need closer follow-up.
Dr. Nelly Tan[/caption]
Dr. Nelly Tan MD
David Geffen School of Medicine
Department of Radiology
UCLA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Tan: Standard of care for prostate cancer diagnosis has been to perform ultrasound guided random (non-targeted) prostate biopsy (TRUS) which is neither sensitive or specific. The main limitation had been our inability to detect and localize prostate cancer through imaging.
Over the past 10 years, MRI has taken center stage for detection and localization of prostate cancer and has shown to improve prostate cancer diagnosis, risk stratification, and staging of the disease. Over the past few years, MRI guided biopsy techniques (in the form of Ultrasound-MRI (US-MRI) fusion and in-bore direct MRI guided biopsy) have been reported. We reported our performance of direct in-bore MRI guided biopsy at UCLA. Our study showed a prostate cancer diagnosis of 59% in all patients and 80% of patients with prostate cancer had clinically significant cancer.









Dr. Firas Abdollah[/caption]
MedicalResearch.com Interview with:
Firas Abdollah, M.D., F.E.B.U.
(Fellow of European Board of Urology) Urology Fellow with the Center for Outcomes Research, Analytics and Evaluation
Vattikuti Urology Institute at Henry Ford Hospital in Detroit
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Abdollah: Cancer screening aims to detect tumors early, before they become symptomatic. Evidence suggests that detection and treatment of early-stage tumors may reduce cancer mortality among screened individuals. Despite this potential benefit, screening programs may also cause harm. Notably, screening may identify low-risk indolent tumors that would never become clinically evident in the absence of screening (overdiagnosis), subjecting patients to the harms of unnecessary treatment. Such considerations are central to screening for prostate and breast cancers, the most prevalent solid tumors in men and women, respectively. These tumors are often slow growing, and guidelines recommend against screening (non-recommended screening) for these tumors in individuals with limited life expectancy, i.e. those with a life expectancy less than 10 years. Unfortunately, our study found that this practice is not uncommon in the US. Using a nationwide representative survey conducted in 2012, we found that among 149,514 individuals 65 years or older, 76,419 (51.1%) received any prostate/breast screening. Among these, 23,532 (30.8%) individuals had a life expectancy of less than 10 years. These numbers imply that among the screened population over 65 years old, almost one in three individuals received a non-recommended screening. This corresponds to an overall rate of non-recommended screening of 15.7% (23,532 of 149,514 individuals).
Another important finding of our study was that there were important variations in the rate of non-recommended screening from state to state; i.e. the chance of an individual older than 65 to receive a non-recommended screening varies based on his/her geographical location in United States.
Finally, on a state-by-state level, there was a correlation (40%) between non-recommended screening for prostate and breast cancer, i.e. states that are more likely to offer non-recommended screening for
Dr. R. Jeffrey Karnes[/caption]
MedicalResearch.com Interview with:
R. Jeffrey Karnes MD
Department of Urology, Mayo Clinic,
Rochester, MN 55905
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Karnes: Cancer recurrence following radical prostatectomy is a concern for men undergoing definitive surgical treatment for prostate cancer. Approximately 20-35% of patients develop a rising prostate specific antigen following radical prostatectomy for clinically localized prostate cancer. PSA monitoring is an important tool for cancer surveillance; however, a standard PSA cutpoint to indicate biochemical recurrence has yet to be established. Over 60 different definitions have been described in literature. This variation creates confusion for the patients and clinicians. By studying a large group of patients who underwent radical prostatectomy at Mayo Clinic, we found that a PSA cutpoint of 0.4 ng/mL is the optimal definition for biochemical recurrence.
Dr. Benjamin Rybicki[/caption]
MedicalResearch.com Interview with:
Benjamin A. Rybicki, Ph.D
Department of Public Health Sciences
Henry Ford Health System
Detroit, MI
Medical Research: What is the background for this study? What are the main findings?
Dr. Rybicki: Inflammation of the prostate gland—prostatitis—is a complex and heterogeneous condition. Two separate meta-analyses have estimated about a 60% increased risk of prostate cancer associated with clinical prostatitis. Most prostatitis, however, is asymptomatic and not fully captured in prevalence surveys. In fact, over 50% of surgical prostate specimens demonstrate some histological evidence of chronic inflammation, which has been generally shown to decrease risk of prostate cancer. The race of a patient may also be a factor as far as how inflammation influences prostate cancer risk. African American men are at greater risk for prostate cancer and demonstrate higher levels of circulating prostate specific antigen (PSA), which can confound the relationship between inflammation and prostate cancer.
In adjusted analyses, African American men with clinical chronic prostatitis had a significant 53% decreased risk of prostate cancer compared with African American men without prostatitis. Clinical prostatitis did not significantly increase prostate cancer risk in white men overall, but it was associated with a significant 3.5-fold increased risk in those who had no evidence of histologic prostatic inflammation. In addition, the investigators found that clinical prostatitis increased prostate cancer risk nearly 3-fold in white men with a low PSA velocity and nearly 2-fold in white men with more frequent PSA testing. PSA level and PSA density did not significantly modify the effect of clinical prostatitis on prostate cancer risk.
Dr. Vitiello[/caption]
MedicalResearch.com Interview with:
Gerardo Vitiello, MD
Emory University School of Medicine
Emory Transplant Center
NYU Langone Medical Center
Department of Surgery
Medical Research: What is the background for this study? What are the main findings?
Dr. Vitiello: Screening for prostate cancer with prostate specific antigen (PSA) levels is highly controversial, as it is a non-specific marker for prostate cancer. A PSA level may be elevated in a variety of disease processes (not only prostate cancer), and even in the general population, the benefit of early intervention for prostate cancer is unclear. In contrast, end stage renal disease (ESRD), where patients no longer have renal function and require dialysis, is a major health problem with a huge impact on a patient’s quality of life. The only cure for ESRD is kidney transplantation, which has been shown to have an enormous health and quality of life benefit for transplant recipients. Transplant centers have rigorously screened candidates for potential malignancy prior to transplantation to ensure that there are no contraindications to receiving a transplant. For the first time, we demonstrate that screening for prostate cancer in kidney transplant candidates is not beneficial, and may actually be harmful, since it delays time to transplant and reduces a patient’s chance of receiving a transplant without an apparent benefit on patient survival.
Dr. Kevin Nead[/caption]
MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil
Dept. of Radiation Oncology
Perelman School of Medicine
University of Pennsylvania
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Nead: There are a growing number of studies suggesting that the use of Androgen Deprivation Therapy (ADT) may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT.
We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive
Prof. Nicolas James[/caption]
MedicalResearch.com Interview with:
Prof Nicholas James
STAMPEDE Trial Chief Investigator
Director of the Cancer Research Centre
Warwick Medical School
University of Warwick Coventry and
Professor of Clinical Oncology
Cancer Centre, Queen Elizabeth Hospital
Birmingham
Medical Research: What is the background for this study? What are the main findings?
Dr. James: The STAMPEDE trial is a multi-arm, multi-stage trials platform testing a range of different therapies in addition to standard of care (SOC) for men commencing long term androgen deprivation therapy (ADT) for newly diagnosed locally advanced or metastatic prostate cancer. These data from the control arm form part of a pair of publications detailing outcomes in the control arm of STAMPEDE and help to make sense of the forthcoming paper on the randomised comparisons currently in press at the Lancet.


