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Today’s fundamental challenge in Prostate cancer screening
Author and Curator: Dror Nir, PhD
Article 8.2.Todays fundamental challenge in Prostate cancer screening
The management of men with prostate cancer is becoming one of the most challenging public health issues in the Western world. It is characterized by: over-diagnosis; over-treatment; low treatment efficacy; treatment related toxicity; escalating cost; and unsustainability [Bangma et al, 2007; Esserman et al, 2009]. How come? Well, everyone accepts that most prostate cancers are clinically insignificant. It is well known that all men above 65 harbor some sort of prostate cancer. Due to the current aggressive PSA-based screening, one in six men will be diagnosed with prostate cancer. Yet, the lifetime risk of dying of prostate cancer is only 3%. The problem is that, once diagnosed with prostate cancer, there is no accurate tool to identify those men that will die of the disease (in my previous post I mentioned 1:37). Currently, screening practices for prostate cancer are relying on the very unspecific prostate-specific-antigen (PSA) bio-marker test to determine which men are at higher risk of harboring prostate cancer and therefore need a biopsy. The existing diagnostic test is a transrectal ultrasound (TRUS) guided prostate biopsy aimed at extracting representative tissue from areas where cancer usually resides. This procedure suffers from several obvious faults:
1. Since the imaging tool used (B-mode ultrasound) is poor at detecting malignancies in the prostate, the probability of hitting a clinically significant cancer or missing a clinically insignificant cancer is subject to random error.
2. TRUS biopsy is also subjected to systematic error as it misses large parts of the prostate which might harbor cancer (e.g. apex and anterior zones). 3. TRUS guided biopsies are often unrepresentative of the true burden of cancer as either the volume or grade of cancer can be underestimated.
In the last ten years I was leading the development of an innovative ultrasound-based technology, HistoScanningTM, aimed at improving the aforementioned faults;
In my future posts I will go into more detail on how these imaging modalities fit into routine workflow, how much they stay within budget constraints and what level of promise they bear for promoting personalized medicine. Stay tuned… Footnote: According to the final report by an advisory panel to the USA government: Doctors should no longer offer the PSA prostate cancer screening test to healthy men because they’re more likely to be harmed by the blood draw, and the chain of medical interventions that often follows than be helped; (http://www.usatoday.com/news/health/story/2012-05-21/prostate-cancer-screening-test-harmful/55118036/1)But then; what should be offered instead?
Other posts on this Scientific Website addressing Prostate Cancer
Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?
Department of Urology, University of Michigan, Ann Arbor, Michigan
Received 17 October 2011 published online 14 May 2012.
Purpose
Minimally invasive nephron sparing surgery is gaining popularity for small renal masses. Few groups have evaluated robot-assisted partial nephrectomy compared to other approaches using comparable patient populations. We present a matched pair analysis of a heterogeneous group of surgeons who performed robot-assisted partial nephrectomy and a single experienced laparoscopic surgeon who performed conventional laparoscopic partial nephrectomy. Perioperative outcomes and complications were compared.
Materials and Methods
All 249 conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010 were reviewed from our prospectively maintained institutional database. Groups were matched 1:1 (108 matched pairs) by R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score, transperitoneal vs retroperitoneal approach, patient age and hilar nature of the tumor. Statistical analysis was done to compare operative outcomes and complications.
Results
Matched analysis revealed that nephrometry score, age, gender, tumor side and American Society of Anesthesia physical status classification were similar. Operative time favored conventional laparoscopic partial nephrectomy. During the study period robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to those of the experienced conventional laparoscopic group. Postoperative complication rates, and complication distributions by Clavien classification and type were similar for conventional laparoscopic and robot-assisted partial nephrectomy (41.7% and 35.0%, respectively).
Conclusions
Robot-assisted partial nephrectomy has a noticeable but rapid learning curve. After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon. Robot-assisted partial nephrectomy likely improves surgeon and patient accessibility to minimally invasive nephron sparing surgery.
Similar outcomes for robot-aided, conventional nephrectomy June 22, 2012 in Other Robot-assisted and conventional laparoscopic partial nephrectomies have similar outcomes and complication rates, according to a study published in the July issue of The Journal of Urology. (HealthDay) — Robot-assisted and conventional laparoscopic partial nephrectomies have similar outcomes and complication rates, according to a study published in the July issue of The Journal of Urology. Ads by Google Prostate Cancer Treatment – Expert Prostate Cancer Treatment & Care – View Video to Learn More! – http://www.TuftsMedicalCenter.tv Prostate Cancer Treatment – Learn about Watchful Waiting. Get a Second Opinion at BIDMC. – http://www.BIDMC.org Jonathan S. Ellison, M.D., from the University of Michigan in Ann Arbor, and colleagues compared perioperative outcomes and complications from conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010. Robot-assisted partial nephrectomies were performed by a heterogeneous group of surgeons, while a single experienced laparoscopic surgeon performed the conventional procedures. One hundred eight pairs of patients were matched by age, hilar nature of the tumor, approach, and R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score. The researchers found that nephrometry score, age, gender, tumor side, and American Society of Anesthesia physical status classification were similar between the groups. Conventional laparoscopic partial nephrectomy had better operative time. Robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to the conventional laparoscopic group. The postoperative complication rates and complication distributions by Clavien classification and type were similar for both groups (41.7 percent for the conventional group and 35.0 percent for the robot-assisted group). “Robot-assisted partial nephrectomy has a noticeable but rapid learning curve,” write the authors. “After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon.” More information: Abstract Full Text (subscription or payment may be required) Journal reference: Journal of Urology
What does your PSA score, level, reading, test mean?
By itself, a PSA reading does not mean very much. There are many possible causes of the rise in the PSA reading. The most common of these reasons is an enlarged, inflamed, or infected prostate. So a high PSA score does not necessarily indicate prostate cancer.
Unfortunately there is no failsafe test or methods at this time that can differentiate between a high PSA level caused by inflammation of the prostate or infection of the prostate or prostate cancer. At best doctors use a statistical model, which seeks to predict your chances of having prostate cancer. But that is purely a statistical construct and does not actually predict your specific and personal situation at all.
Nonetheless, an elevated PSA reading should not be ignored. It is a good indicator, certainly the best we have, and you should take precautionary action.
If you have a high PSA reading you need to return your prostate back to good health. You need to make important changes to your diet. You also need to have regular exercise. A third and equally important part of my recommendation is to take appropriate natural supplements.
I provide a roadmap in my guide “All about the Prostate”. Most men who follow my roadmap will see their PSA levels come down. It will return their prostate to good health.
ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have received prior chemotherapy containing docetaxel.
IMPORTANT SAFETY INFORMATION
Contraindications – ZYTIGA® (abiraterone acetate) may cause fetal harm (Pregnancy Category X) and is contraindicated in women who are or may become pregnant.
Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess –Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in hypertension, hypokalemia, and fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure because these patients were excluded from the randomized clinical trial. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.
Adrenocortical Insufficiency (AI) – AI has been reported in clinical trials in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.
Hepatotoxicity – Increases in liver enzymes have led to drug interruption, dose modification, and/or discontinuation. Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function.
Food Effect – ZYTIGA® must be taken on an empty stomach. Exposure of abiraterone increases up to 10-fold when abiraterone acetate is taken with meals. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.
Adverse Reactions – The most common adverse reactions (≥ 5%) are joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, fractures and upper respiratory tract infection.
Drug Interactions – ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. Additionally, abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.
Use in Specific Populations – The safety of ZYTIGA® in patients with baseline severe hepatic impairment has not been studied. These patients should not receive ZYTIGA®.
On August 5, 2008, the US Preventive Services Task Force (USPSTF) recommended against screening men 75 years or older for prostate cancer.1 For men younger than 75 years, the USPSTF maintained its previous recommendation: “ . . . the evidence is insufficient to recommend for or against routine screening for prostate cancer. . . ”2 (p915) (although this recommendation was changed to “do not screen” younger men in the 2011 guidelines). This study evaluates trends in prostate cancer incidence following the release of the 2008 USPSTF recommendation. If the revised recommendation led to a decline in prostate cancer screening rates, there should be a corresponding decline in the incidence of early-stage tumors among men 75 and older relative to trends in the incidence of late-stage tumors and early-stage tumors in younger men.
Methods
I measured trends in prostate cancer incidence rates by age group using the Surveillance, Epidemiology and End Results (SEER) 18 registry data, covering 28% of the US population. The SEER registries collect information on all newly diagnosed cancer cases in their respective catchment areas.
Prostate tumors were identified using International Classification of Diseases for Oncology version 3 code 619. I classified cases by stage at diagnosis using the derived American Joint Committee on Cancer summary stage variable: early (T1 or T2), late (T3 or T4), or unknown. I grouped patients into 3 age categories (30-64 years, 65-74 years, and 75 years and older). I calculated incidence rates per 100 000 persons, standardized within age categories by age (in 5-year age groups), race (white, black, American Indian, or other), and ethnicity (Hispanic or not Hispanic) to the 2009 population. I used an unpaired t test for proportions to assess the significance of differences in rates between years. The data were analyzed in Stata version 11 (StataCorp) statistical software.
Results
The data included 254 184 prostate cancer cases. There were 198 417 early-stage cases, 34 695 late-stage cases, and 21 072 cases of unknown stage. There were 109 053 cases (all stages) among men aged 30 to 64 years, 91 868 cases among men aged 65 to 74 years, and 53 263 cases among men 75 years and older.
The Figure displays the age and race/ethnicity-adjusted incidence rates of early-stage tumors among men aged 65 to 74 years (the upper line) and 75 years and older (the lower line). The trend lines generally mirror each other, but there is a sudden decrease in the incidence of early-stage tumors among men 75 and older after the release of the revised USPSTF recommendation.
Figure. Trends in the incidence of early-stage prostate tumors by age group. Rates are standardized by 5-year age groups and race/ethnicity to the 2009 population. Source: analysis of Surveillance, Epidemiology and End Results (SEER) 18 registry data. USPSTF indicates US Preventive Services Task Force.
Between 2007 and 2009, the adjusted incidence rate for early-stage tumors among men 75 years and older decreased from 443 to 330 per 100 000 (−25.4%; P < .001). The absolute number of cases declined from 8137 to 6162. The incidence of late-stage tumors decreased from 83 to 71 (−14.3%; P < .001), and the incidence of tumors with unknown stage decreased from 124 to 103 (−16.8%; P < .001). The incidence of early-stage tumors among men aged 65 to 74 years decreased from 697 to 591 (−15.2%; P < .001). The incidence of early-stage tumors among men aged 30 to 64 years decreased from 105 to 93 (−11%; P < .001). Incidence trends for all age and stage groups are given in the eTable.
In the past, clinicians and the public have heeded the advice of the United States Preventative Services Task Force (USPSTF) about prostate cancer screening, suggests researchpublished online July 23 in the Archives of Internal Medicine.
After the group’s 2008 guidance, which recommended against screening men older than 75 years, the incidence of early-stage disease in older men plunged 25% in the United States.
“There was an immediate decline in the incidence of early-stage prostate cancer tumors among men 75 years and older after the USPSTF recommended against screening this group,” writes author David Howard, PhD, from the Department of Health Policy and Management at Emory University in Atlanta, Georgia.
The incidence of early-stage disease is an indicator of the amount of prostate-specific antigen (PSA) testing in a population, he explained.
Dr. Howard found that from 2007 to 2009, the adjusted incidence rate for early-stage tumors in men 75 years and older decreased from 443 to 330 per 100,000 (−25.4%; P < .001). The absolute number of cases declined from 8137 to 6162.
Dr. Howard used data from the Surveillance, Epidemiology, and End Results (SEER) 18 registry, which collects information on newly diagnosed cancer cases in catchment areas.
He challenges recent results that indicated that there was no change in PSA screening rates from 2005 to 2010 (JAMA. 2012;307:1692-1694). The data source for that study was the National Health Interview Surveys, in which American residents self-report health behaviors and diseases. “Self-reported PSA testing measures have poor sensitivity and specificity,” scolds Dr. Howard.
An immediate question arises from Dr. Howard’s analysis: Will it happen again because of the 2012 USPSTF recommendation against routine testing for all healthy men?
In an unrelated essay (J Clin Oncol. 2012;30:2581-2584), a group of experts assert that the answer is no.
The USPSTF’s “blanket rejection” of the PSA test is “unlikely to influence practice,” according to Sigrid Carlsson, MD, PhD, from the Memorial-Sloan Kettering Cancer Center in New York City and Göteborg University in Sweden, and colleagues. Dr. Carlsson and her fellow experts wrote an essay criticizing the new USPSTF guideline for a number of “very important errors,” as reported by Medscape Medical News.
“PSA testing is not likely to go away,” wrote Dr. Carlsson and coauthors.
Dr. Howard voiced similar thoughts in an email to Medscape Medical News.
“Physicians are probably more willing to discontinue screening older patients. There might be more resistance to discontinuing screening among younger, healthier men,” he said.
But Dr. Howard also said: “I think it will have an impact. There is growing publicity about the problem of ‘overdiagnosis’, which might make physicians and some patients more receptive to the USPSTF recommendation.”
The recently published PIVOT study might also contribute to the way the new guidance is received, noted Dr. Howard. This major randomized controlled trial found that prostatectomy did not improve survival significantly, compared with observation, in men with localized disease. “This research also casts doubt on the benefits of early detection, which may amplify the impact of the USPSTF recommendation,” said Dr. Howard about PIVOT.
Nonetheless, “many men will continue to receive regular PSA tests,” he added.
More Details
In addition to finding that the rate of early-stage prostate cancers dropped among older men after the 2008 recommendation, Dr. Howard found that other indicators of PSA testing also dropped.
The incidence of late-stage tumors decreased by 14.3% (P < .001), and the incidence of tumors of unknown stage decreased by 16.8% (P < .001). The incidence of early-stage tumors in men 65 to 74 years decreased by 15.2% (P < .001); in men 30 to 64 years, the incidence decreased by 11% (P < .001).
Overall, Dr. Howard found that 254,184 prostate cancer cases were newly diagnosed during the study period. There were 198,417 early-stage cases, 34,695 late-stage cases, and 21,072 cases of unknown stage. There were 109,053 cases (all stages) in men 30 to 64 years of age, 91,868 cases in men 65 to 74 years, and 53,263 cases in men 75 years and older.
As noted above, the incidence rate trends turned sharply downward in 2009, after the 2008 USPSTF report.
US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(3):185-191
Prasad SM, Drazer MW, Huo D, Hu JC, Eggener SE. 2008 US Preventive Services Task Force recommendations and prostate cancer screening rates. JAMA. 2012;307(16):1692-1694
4
Hall HI, Van Den Eeden SK, Tolsma DD, et al. Testing for prostate and colorectal cancer: comparison of self-report and medical record audit. Prev Med. 2004;39(1):27-35
5
Chan EC, Vernon SW, Ahn C, Greisinger A. Do men know that they have had a prostate-specific antigen test? accuracy of self-reports of testing at 2 sites. Am J Public Health. 2004;94(8):1336-1338
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Guerra CE, Jacobs SE, Holmes JH, Shea JA. Are physicians discussing prostate cancer screening with their patients and why or why not? a pilot study. J Gen Intern Med. 2007;22(7):901-907
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Linder SK, Hawley ST, Cooper CP, Scholl LE, Jibaja-Weiss M, Volk RJ. Primary care physicians’ reported use of pre-screening discussions for prostate cancer screening: a cross-sectional survey. BMC Fam Pract. 2009;1019
New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests
Reporter: Prabodh Kandala, PhD
Article 8.4.New Prostate Cancer Screening Guidelines Face a Tough Sell Study Suggests
Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter serious pushback from primary care physicians, according to results of a survey by Johns Hopkins investigators.
In a survey of 125 primary care doctors, the researchers found that while doctors agreed with older recommendations to curtail routine screening in men over age 75 and among those not expected to live 10 or more years, a large number said they faced significant barriers to stopping PSA testing in men who had been receiving it regularly. The most frequently cited reason by 74.4 percent of physicians was, “My patients expect me to continue getting yearly PSA tests,” followed by 66 percent of them who said, “It takes more time to explain why I’m not screening than to just continue screening.” More than half of those surveyed in the new study believed that, “By not ordering a PSA, it puts me at risk for malpractice.”
The survey was conducted in November 2011, right after draft recommendations were made to end routine screening of all men, but before last week, when the draft recommendations were officially approved.
“It can be very difficult for doctors to break down the belief that all cancer screening tests are invariably good for all people all the time,” says Craig E. Pollack, M.D., M.H.S., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine, and leader of the study published online in the journal Cancer. “Everyone agrees that PSA screening isn’t as good as we want it to be. If we had a test that was a slam dunk, it would be different. But now we know that for many men, the benefits may be small and the harms significant.”
Each year, more than 33,000 American men die of prostate cancer, and 20 million get the PSA test to detect the disease early.
According to the USPSTF, evidence suggests the potential harms caused by PSA screening of healthy men as a means of identifying prostate cancer outweigh its potential to save lives and that routine annual screening should be eliminated in the healthy. Elevated PSA readings are not necessarily evidence of prostate cancer, and can lead to unnecessary prostate biopsy. In addition, even when biopsies reveal signs of prostate cancer cells, evidence shows that a large proportion will never cause harm, even if left untreated. The disease in older men often progresses slowly so that those who have it frequently die of other causes.
Treatments for prostate cancer can include the removal of the prostate, radiation or other therapies, each of which has the potential to cause serious problems like erectile dysfunction, complete impotence, urinary incontinence or bowel damage. And men who choose to “watch and wait” after elevated PSA readings must live with the anxiety of knowing they have an untreated cancer that could start to progress.
In the new study, Pollack and his colleagues found that while most physicians said they took age and life expectancy into account when deciding to order PSA screening, many also said they had a hard time estimating life expectancy in their patients and could use a better tool. H. Ballentine Carter, M.D., a professor of urology at Johns Hopkins and the senior investigator on the study, is planning to investigate the potential of individualized prostate cancer screening recommendations. Specifically, he and colleagues plan to create a decision-making tool that incorporates age, life expectancy, family history and prior PSA results in order to help doctors and their patients make better choices for prostate cancer screening.
In another report derived from results of Pollack’s and Carter’s survey, published in April in the Archives of Internal Medicine, the researchers say nearly half of the providers agreed with the new USPSTF recommendations to eliminate routine screening for healthy men. Still, less than two percent said they would no longer order routine PSA screening in response to the draft recommendations; 21.9 percent said they would be much less likely to do so; 38.6 percent said they would be somewhat less likely to do so; and 37.7 percent said they would not change their screening practices.
“Men often expect PSA screening to be part of their annual physical,” Pollack says. “To change their minds, we need to address their perceptions about screening, allow time for screening discussions and reduce concerns regarding malpractice litigation.”
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