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Prostate Cancer Surveillance To screen or NOT to screen? Jackie Keedy, MD Primary Care Conference May 26, 2011 Outline Introduction cases US Preventative Services Task Force Guidelines National Comprehensive Care Network Guidelines Talking points for discussion with your patient A little data, including “The New Swedish Study” Conclusion or Confusion? Case 1. 52 year old Caucasian man at his PCPs office getting annual physical Asks to be screened for prostate cancer because his father had prostate cancer at age 74 He was found to have a PSA of 4.1 ng/ml Rechecked one month later5.3 ng/ml Underwent biopsy, was found to have prostate cancer had surgery & radiation Case 2. 54 year old healthy, athletic Caucasian man No FH of prostate cancer Serum PSA done as part of annual physical PSA elevated, so sent to urology Underwent transrectal biopsy Became febrile 1-2 days after bx, 103-104, and was hospitalized for sepsis Discharged with 6 weeks of IV antibiotics Case 3. 55 yo obese African American man No FH of prostate cancer DRE indeterminate PSA 250 ng/ml Being referred to urology MKSAP Question An 80-year-old man is evaluated after a serum prostatespecific antigen (PSA) level of 5.7 ng/mL (5.7 µg/L) was noted during a community screening program. He has no symptoms related to the genitourinary system and denies bone pain, weight loss, or any change in his health status. The patient has hypertension and hypercholesterolemia and underwent four-vessel coronary artery bypass graft surgery 5 years ago. His current medications are hydrochlorothiazide, atenolol, lisinopril, pravastatin, and low-dose aspirin. On physical examination, the patient is afebrile, blood pressure is 140/80 mm Hg, and the pulse rate is 72/min and regular. The lungs are clear, and the abdomen is soft and nontender. There is trace pedal edema in the lower extremities. Which of the following is the most appropriate next step in management? A B C D Bone scan Repeat PSA Transrectal prostate biopsy Observation Observation, right! In men age 75 years or older, the U.S. Preventive Services Task Force found adequate evidence that the incremental benefits of treatment for prostate cancer detected by screening are small to none. USPSTF Guidelines Prostate Cancer Summary of Recommendations The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years. The USPSTF recommends against screening for prostate cancer in men age 75 years or older. Harms of Detection and Early Treatment The USPSTF found convincing evidence that treatment for prostate cancer detected by screening causes moderate-to-substantial harms, such as erectile dysfunction, urinary incontinence, bowel dysfunction, and death. These harms are especially important because some men with prostate cancer who are treated would never have developed symptoms related to cancer during their lifetime. There is also adequate evidence that the screening process produces at least small harms, including pain and discomfort associated with prostate biopsy and psychological effects of false-positive test results. Ok, but what if they have a risk factor? Older men, African-American men, and men with a family history of prostate cancer are at increased risk for diagnosis of and death from prostate cancer. Unfortunately, the previously described gaps in the evidence regarding potential benefits of screening also apply to these men. Let’s consider our three men Case 1. 52 year old healthy Caucasian man, + FH Case 2. 54 year old healthy young Caucasian man, - FH Case 3. 55 obese African American man, - FH According to the USPSTF, we should NOT have screened any of them… To Screen or NOT to Screen? American Cancer Society American Urological Association The United States Preventive Services Task Force Many European Cancer Societies National Comprehensive Cancer Network www.nccn.org Suggested “Talking Points” for Discussion: The Pros and Cons of PSA testing Prostate cancer is the most common cancer in men (older men) Accounts for 29% of all malignancies in male patients Second most common cause of cancer-related deaths in men 218,900 new cases in US each year, about 27,000 deaths related to prostate cancer annually Men in the US have a 1 in 6 chance Talking points Men who have regular PSA tests have a higher chance of finding out Men who do NOT have PSA tests have a lower chance but a higher probability of having more advanced cancer when ultimately diagnosed The PSA test can detect the majority of prostate cancers earlier than a DRE when a man has no symptoms African-American men and men with a father, brother, or son with prostate cancer have a higher risk Native American and Asian-American men have a substantially lower risk More Talking Points Many prostate cancers grow slowly. Consequently, many men with prostate cancer may die of something else before their prostate cancers causes any symptoms However, prostate cancers that grow more rapidly can potentially impact overall survival and quality of life Whether a man will die of something else or prostate caner depends on how aggressive the cancer is, how early it is detected, how effectively it is treated, as well as age and other problems Most experts believe that in general men over age 75, or even younger with serious medical problems, have little to gain from a PSA test More talking points (for your 15 minute visit!) Docs disagree about what level of PSA is high enough to do further testing (biopsy) to look for prostate CA Most docs feel men with PSA levels > 4 should have a biopsy, others feel levels >2.5 There is an increasing tendency to focus less on absolute PSA values and to consider changes in PSA over time There is accumulating evidence that men who have a steady rise in their PSA level are more likely to have cancer, and if the rise is rapid, the cancer is more likely to be life threatening Other factors such has patient age and prostate volume (size of gland) are also important to consider when deciding who needs a prostate biopsy Doc, what’s the biopsy like? A prostate biopsy is usually performed using local anesthesia through a probe placed into the rectum through which a needle is placed. Needle takes samples Usually 10-12 samples taken The prostate biopsy, not the PSA test, tells whether or not a man has prostate cancer A prostate biopsy is usually well tolerated and infrequently causes serious problems such as rectal or urinary hemorrhage, infection, or urinary infection Frequency of biopsy complications with 10 core biopsy Hematospermia Hematuria > 1 day Rectal bleeding < 2 days Prostatitis Fever> 38.5 C (101.3 F) Epididymitis Rectal bleeding > 2 days (+/- surgical intervention) Urinary retention Other complications (requiring hospitalization) 37.4% 14.5% 2.2% 1.0% 0.8% 0.7% 0.7% 0.2% 0.3% Well, that sounds like a blast. A PSA test can be abnormal even when a man does NOT have prostate cancer (false +) false + PSA tests can come from other prostate conditions that are not important to find (unless a man has bothersome urinary symptoms) About 1 in 3 men with a high PSA level have prostate cancer The higher the PSA level, the more likely a man will be found to have prostate cancer if a biopsy is performed A PSA test can also be normal even when a man does have prostate cancer (false -) About 1 in 7 men with PSA levels less than 4 have prostate cancer The higher a man’s PSA level is across all PSA ranges from zero on up, the more likely a man is to have prostate cancer. This is true even within the so- called “normal” range. Prostate biopsies aren’t perfect tests, either. Prostate biopsies sometimes miss cancer when it is there. Some docs recommend a second set of biopsies if the first set is negative Others will follow the PSA level and suggest more biopsies only if the level continues to go up We went for it, and we found it. I guess I should be glad we did it? Common treatments are surgery to remove the prostate or radiation treatment to the prostate Surgery has a very small risk of death Both radiation & surgery can cause problems with urinary leakage in some men, but risk is higher with surgery Both radiation & surgery cause problems with getting and keeping an erection in many men. The risk is higher with surgery in the short run, but over the long run, the risk is about the same Radiation also has a risk of causing bowel problems in some men Some men, especially older men with slow-growing cancers, may not need treatments like surgery or radiation for their prostate cancer and can be followed with periodic PSA test and physical exams (watchful waiting, active surveillance or expectant management) Does screening reduce mortality?? It is not clear if screening a man with the PSA lowers his chances of eventually dying of prostate cancer or helps him live longer Also not clear if screening a man with the PSA test lowers a man’s chances of eventually having to deal with complications or prostate cancer (painful spread to bones), but the lower rates of advanced-stage disease at the time of diagnosis and the lower rates of prostate cancer deaths suggest that few men many suffer from advanced disease As a result, docs disagree over the value of screening men with the PSA test However, it is well established that screening has been associated with an unprecedented shift in the stages of prostate cancer at the time of diagnosis More than 75% of cancers are now detected when they are confined to the prostate gland, when current therapies are most effective The actual relationship to PSA testing however remains unknown, but available evidence suggests that the lower mortality rates may be due, at least in part, to PSA testing European Randomized Study of Screening for Prostate Cancer ERSPC trial released in 2009: Level 1 evidence of PSA screening Initiated in the 1990’s to evaluate the effect of PSA testing on death rates from prostate cancer Trial involved 182,000 men between ages of 50-74 in 7 European countries Random assignment to a group that was offered PSA screening at an average of once every 4 years OR a control group that did not receive such screening Death from prostate cancer was primary outcome Median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group There were 214 prostate cancer deaths in the screening group, and 326 in the control group The rate ratio for death from prostate cancer in the screening group, compared to control group was 0.80 (95% confidence interval 0.65-0.98); adjusted P=0.04 The researchers concluded that PSA-based screening reduced the rate of death from prostate cancer by 20% However, they also concluded that this was associated with a high risk of overdiagnosis Statistically, 1,410 men would need to be screened and 48 men would need to be treated to prevent one death from prostate cancer United States Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial 76,693 men between the ages of 55 and 74 Randomly assigned to annual screening with PSA and DRE or to usual care A PSA level above 4.0 ng/mL or an abnormal DRE were indications for biopsy. A high proportion of men in the control group underwent PSA testing (52 percent in the sixth year of the study) and over 40 percent of study subjects had undergone PSA testing within three years before enrolling in the trial. In contrast to the ERSPC, after seven years of follow-up there was no reduction in the primary outcome of prostate cancer mortality (50 versus 44 deaths in the screening and control groups, respectively; rate ratio 1.13, 95% CI 0.75-1.70). Cancer detection in the screening group was significantly higher than in the control group (2820 versus 2322, rate ratio 1.22, CI 1.16-1.29). Randomized prostate cancer screening trial: 20 year follow-up To assess whether screening for prostate cancer reduces prostate cancer specific mortality. All men aged 50-69 in Sweden 1494 men were randomly allocated to be screened by including every sixth man from a list of dates of birth. These men were invited to be screened every third year from 1987 to 1996. There were 85 cases (5.7%) of prostate cancer diagnosed in the screened group and 292 (3.9%) in the control group. The risk ratio for death from prostate cancer in the screening group was 1.16 (95% confidence interval 0.78 to 1.73). In a Cox proportional hazard analysis comparing prostate cancer specific survival in the control group with that in the screened group, the hazard ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P=0.13) After 20 years of follow-up the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group. American Urological Association (AUA) 2011 Annual Scientific Meeting May 16, 2011 (Washington, DC) ”Single PSA Test Before Age 50 Predicts Long-Term Risk” 20,000 Swedish men obtained PSA information for 1167 men men with a PSA value above 1.5 ng/mL between the ages of 45 and 49 years account for nearly half of the prostate cancer deaths over the next 30 years or so Only 10% of the men in the study had such high PSA values at this relatively young age Single PSA test, continued On the basis of a PSA value obtained in a man's 40s, you can stratify risk This study shows whom we really need to focus on… The young men in this top 10% need aggressive follow-up, such as reminder phone calls for doctors' appointments, and should have either annual or biennial PSA tests In the study, which had a median follow-up of 27 years, 44% of all of the prostate cancer deaths occurred in this top 10% of men. In other words, a small proportion of the men accounted for a lot of the prostate cancer deaths. Not jumping to new guidelines…but New data call into question the "typical" recommendations from professional groups about PSA testing because the recommendations do not involve risk stratification. Risk-stratifying screening has 2 major benefits: it will reduce over diagnosis in men at low risk for prostate cancer death it will improve compliance with screening in men who will benefit the most Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer “The New Swedish Study” Suggests that radical prostatectomy is better that “watchful waiting” for treatment of young men with low-risk prostate cancer Contradicts a US trend toward holding off on surgery and monitoring men who have lowrisk cancers with “active surveillance” The New Swedish Study, details An update of a 2008 report with an additional 3 years of data on nearly 700 men who volunteered for the trial up to 15 years ago; all had early-stage prostate cancer at the beginning The study found 38% fewer prostate cancer deaths among men randomly assigned to the surgery group versus watchful waiting Men who had surgery had 41% lower risk of growth spreading throughout their body, and 66% less risk of growth within prostate Survival benefits were restricted to men under 65 Surgery saved one life for every seven men who had prostatectomies (considered favorable!) Applied to men with tumors considered low risk Important points to think about Only 1 of 20 men in the Swedish study had a prostate cancer diagnosis based on high PSA level Almost 90 percent had tumors their doctors could feel on DRE In the US, most prostate cancers are identified by PSA screening, and less than half have palpable tumors Many prostate cancers found by PSA are likely to be slow growing (9 out of 10 prostate cancers in the US are considered low risk) “low risk” in Swedish study mean higher-risk than current “low risk” men diagnosed in the US Another important point Watchful waiting does not mean the same thing as active surveillance Watchful waiting means we are not going to treat you know and if you progress clinically, we will treat you with hormone therapy; not with curative intent Active surveillance means observing the patient in a proactive way, with regularly scheduled biopsies. If there is a sign the cancer is progressing, doctors currently would treat with intent to cure, using surgery, radiation or both Last important point Both surgical techniques and radiation therapy technology have improved since the Swedish study was done So there is reason to think men followed with active surveillance and treated when necessary would fare better than the “watchful waiting” group in new study Clear as Mud There are advantages and disadvantages to having a PSA test, and there is no “right” answer about PSA testing for everyone Each man should make an informed decision about whether the PSA test is right for him Screening for and the treatment for prostate cancer must be tailored to the individual man As a PCP, most patients will do what you suggest, so figure out your stand Remember that prostate cancer is the 2nd leading cause of death of men While you are screening for other cancers, think about whether you want to screen for prostate cancer References Bill-Axelson, A. et al. (2011). Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer. N Engl J Med 2011; 364:1708-1717 Knox, R. (2011, May 4). Swedish Study Finds Surgery For Prostate Cancer Better Than Waiting. Message posted to www.npr.org MKSAP 15. Hematology and Oncology. American College of Physicians. Mulcahy, N. Single PSA Test Before Age 50 Predicts Long-Term Risk. Medscape News: Internal Medicine. American Urological Association (AUA) 2011 Annual Scientific Meeting. Abstract 986. Presented May 16, 2011. National Comprehensive Cancer Network. (2011). Prostate Early Detection Practice Guidlines. Retrieved May 10, 2011, from www.nccn.org Uptodate.com USPSTF. (2008). Screening for Prostate Cancer. Retrieved May 20, 2011, from http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm Sandblom, G. et al. (2011). Randomized Prostate Cancer Screening Trial: 20 year follow-up. BMJ; 342:d1539