Clinical Practice
Screening for Prostate Cancer
N Engl J Med 2011; 365:2013-2019November 24, 2011
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- Article
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
A 50-year-old, non-Hispanic white man comes for a new-patient appointment and wants to discuss prostate-cancer screening. He has no family history of prostate cancer and says that he does not have any lower urinary tract symptoms. What would you advise?
The Clinical Problem
Prostate cancer is the most frequently diagnosed cancer other than skin cancer and the second leading cause of death from cancer in men in the United States.1 In 2011, prostate cancer is expected to be diagnosed in an estimated 240,000 men and to cause nearly 34,000 deaths.1 After peaking in the early 1990s, by 2007 the age-adjusted incidence of prostate cancer had declined to 165.8 cases per 100,000 men and mortality rates had declined to 23.5 deaths per 100,000 men2 (Figure 1Figure 1
Age-Adjusted Incidence of and Mortality from Prostate Cancer in the United States, 1975–2007.). Between 1999 and 2006, at the time of diagnosis, about 80% of prostate cancers were clinically confined to the prostate, and only 4% had metastasized.2 The strongest risk factors for prostate cancer are older age, a positive family history, and black race. The median age at diagnosis is 67 years, and the median age at death is 81 years.2 The risk of prostate cancer is two times as high among patients who have a first-degree relative with a prostate-cancer diagnosis as among patients who do not have a first-degree relative with this diagnosis.3 Black men have the highest incidence rate of prostate cancer in the United States and are more likely to receive a diagnosis of prostate cancer at an advanced stage than men in any other racial or ethnic group.2
In the United States, approximately 90% of prostate cancers are detected by means of screening.4 After the introduction of prostate-specific antigen (PSA) testing, the lifetime risk of receiving a diagnosis of prostate cancer nearly doubled, increasing from approximately 9% in 19855 to 16% in 2007.2
The great majority of men with a diagnosis of prostate cancer die from other causes. Autopsy series suggest that 30% of men older than 50 years of age and 70% of those older than 70 years of age have occult prostate cancer. 6 An analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registry and from Medicare claims evaluated outcomes of almost 90,000 older men who received a diagnosis of early-stage prostate cancer between 1992 and 2002 and who were cared for without attempted curative therapy.7 The 10-year risk of death from prostate cancer ranged from approximately 8% among men with well-differentiated tumors to 26% among those with poorly differentiated tumors. The 10-year risks of death from competing causes were consistently nearly 60%, regardless of the tumor grade.
Strategies and Evidence
Screening Tests
The rationale for screening is that early detection and treatment of asymptomatic cancers could extend life, as compared with treatment at the time of clinical diagnosis. Effective cancer screening requires an accurate, reliable, and easy-to-administer test that detects clinically important cancers at a preclinical stage and the availability of effective treatment that results in better outcomes when administered early, rather than after signs or symptoms of disease have developed.
For many years, the digital rectal examination was the primary screening test for prostate cancer. However, this test has considerable interexaminer variability,8 and the majority of cancers detected by means of digital rectal examination are at an advanced stage.9 In the late 1980s, PSA testing, which was initially developed for prostate-cancer surveillance, was rapidly and widely adopted for screening; by 2001, a population-based survey in the United States showed that 75% of men 50 years of age or older had undergone PSA testing.10 The widespread use of PSA testing was based on its increased detection of early-stage cancer, as compared with digital rectal examination; there was no evidence that testing reduced the risk of death from prostate cancer.
Initially, PSA values above 4.0 ng per milliliter were considered abnormal, though lower cutoff levels have subsequently been proposed. The estimated diagnostic performance of PSA testing according to the cutoff level is shown in Table 1Table 1
Diagnostic Performance Characteristics of PSA Testing, According to Cutoff Level.. Most abnormal PSA values are false positive results that can be caused by benign prostatic hyperplasia, prostatitis or cystitis, ejaculation, perineal trauma, or the recent use of instruments for testing or surgery in the urinary tract. Moreover, a normal PSA value does not rule out prostate cancer; in the control group in the Prostate Cancer Prevention Trial, prostate cancer was detected in 15% of men with normal results on digital rectal examination and PSA values of 4.0 ng per milliliter or less (and in 9% of men with normal results on digital rectal examination and PSA values ≤1.0 ng per milliliter) who underwent a prostate biopsy at the end of the study.12 Numerous approaches have been proposed to improve the diagnostic accuracy of the PSA test, including measuring PSA velocity (change over time), levels of free and protein-bound PSA, PSA density (the PSA level divided by the prostate volume), and the use of cutoff values for PSA levels that are specific to the patient's age and race or ethnic group.13 However, the clinical usefulness of these strategies remains unproved.
Potential Benefits of Screening
Ecologic and case–control data have suggested associations between PSA testing and a decrease in mortality from prostate cancer, but the findings are conflicting.14-17 SEER data show steadily declining age-adjusted mortality rates from prostate cancer since 1994, though an absolute decrease of only 10.4 deaths per 100,000 men2 (Figure 1). Mathematical models have estimated that 45 to 70% of the observed decrease in mortality could be attributable to PSA screening.18
Results of recently reported randomized trials, however, have not convincingly established the value of PSA screening (see Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). Although the European Randomized Study of Screening for Prostate Cancer (ERSPC; Current Controlled Trials number, ISRCTN49127736) showed that screening resulted in a moderately reduced mortality from prostate cancer,19 the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (ClinicalTrials.gov number, NCT00002540) showed no benefit.20
The ERSPC, conducted in seven European centers, randomly assigned 182,160 men who were between the ages of 50 and 74 years to PSA screening every 4 years (except every 2 years in Sweden) or usual care (no PSA screening).19 The initial mortality findings were based on data for 162,243 men who were between the ages of 55 and 69 years. During a median follow-up of 9 years, prostate cancer was detected in 8.2% of the screened subjects as compared with 4.8% of the control subjects (a 71% increase). Mortality from prostate cancer was 20% (95% confidence interval [CI], 2 to 35) lower in the screening group. However, the absolute difference was only 0.7 deaths per 1000 men, suggesting that 1410 men would need to be screened approximately twice over a period of 9 years to prevent 1 death from prostate cancer. Furthermore, prostate cancer would need to be diagnosed in 48 men to prevent that 1 death. Screening did not result in decreased overall or prostate-cancer mortality among men between the ages of 50 and 54 years or those between the ages of 70 and 74 years.
Subsequent analyses of these data have suggested that the benefit of regular screening might be higher after adjustment for nonadherence (estimated relative reduction in mortality, 27%) and after additional adjustment for contamination (PSA screening in persons not randomly assigned to screening; estimated relative reduction in mortality, 31%).21 However, even these post hoc analyses, which are more susceptible to bias than the primary intention-to-treat analysis, suggested only a small absolute survival benefit.
Results from the Göteborg, Sweden, randomized screening trial, which included ERSPC subjects, showed a greater reduction in the risk of death from prostate cancer with screening (44%; 95% CI, 18 to 61) among men 50 to 64 years of age who were followed for a median of 14 years.22 This finding corresponds to a number needed to screen of 293 and a number needed to diagnose of 12 to prevent one death from prostate cancer. Possible explanations for this finding include more frequent PSA testing, younger age range, longer follow-up at this site, and simply chance (the 95% confidence interval for this site-specific estimate included the point estimate for the multicenter analysis). Studies have estimated that PSA screening detects cancers 5 to 10 years before they can be detected clinically (the lead time),23 and survival curves after treatment for clinically detected cancers did not diverge significantly for at least 5 years.24 Accordingly, a modeling study extrapolating ERSPC data from all sites over a longer follow-up period projected an increasing screening benefit over time25; by year 12, the estimated number needed to screen to prevent one death from prostate cancer would be 503, and the number needed to diagnose would be 18.
In contrast, the PLCO trial, which randomly assigned 76,693 men, who were between the ages of 55 and 74 years at enrollment, to annual PSA testing for 6 years and annual digital rectal examination for 4 years or to no screening, did not show any reduction in overall or prostate-cancer mortality with screening.20 Screening resulted in a significant increase in cancer detection, with 22% more cancers diagnosed in the screened group than in the control group (2820 vs. 2322) at 7-year follow-up. Cancers in the screening group had more favorable tumor characteristics than cancers in the control group, including earlier stages and lower Gleason scores (the Gleason score is the sum of the two most common histologic patterns or grades in a prostate tumor, each of which is graded on a scale of 1 to 5, with 5 indicating the most aggressive pattern). Nonetheless, prostate-cancer mortality was not reduced in the screening group as compared with the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70).
However, several factors could have biased the results of the PLCO trial toward the null hypothesis. More than 40% of enrolled subjects had undergone at least one PSA test in the 3 years before study enrollment. Serial PSA testing is associated with reduced rates of prostate-cancer detection as well as an earlier stage and less aggressive tumor characteristics at the time of diagnosis.26 Given the long lead time associated with PSA testing, the 7-year follow-up might have been insufficient to show a survival benefit. The study also had substantial contamination, with more than half of the subjects in the control group reporting PSA testing in year 6. In addition, only 40% of men in the screening group who had abnormal initial PSA values actually underwent prostate biopsy, and the proportions were even lower during subsequent screening rounds.26
Potential Harms of Screening
Abnormal PSA tests lead to biopsies, which can infrequently cause bleeding, pain, or infection.11 Undergoing biopsy can be stressful, and some men have persistent anxiety regarding possible cancer, despite negative biopsy results.27 Mathematical models estimate that 23 to 42% of PSA-detected cancers are overdiagnosed, because on the basis of life expectancy at the time of diagnosis and the natural history of the cancer in the absence of screening, it would not be expected to cause clinical problems during the patient's lifetime.23 Aggressive treatment of these cancers is associated with unnecessary risks of urinary, sexual, and bowel dysfunction, which can adversely affect the quality of life.28
Treatment Trials
Paradoxically, PSA testing became widespread before any data supported the benefit of aggressively treating early-stage cancer. In 2002, the Scandinavian Prostate Cancer Group Study Number 4, which randomly assigned 695 men younger than 75 years of age who had early-stage prostate cancer to radical prostatectomy or watchful waiting, showed a relative hazard reduction for death from prostate cancer of 50% among those assigned to prostatectomy (4.6% vs. 8.9%), during a median follow-up of 6.2 years.24 The mortality benefit persisted through 15 years of follow-up.29 However, no survival benefit was seen for men who were older than 65 years of age at the time of diagnosis and treatment. Since only about 5% of the tumors were detected by screening, and more than 75% were palpable, it is questionable whether these results are applicable to patients in the United States.
The Prostate Cancer Intervention versus Observation Trial (NCT00007644) randomly assigned 731 men with early-stage prostate cancer to either radical prostatectomy or watchful waiting.30 Three fourths of tumors were diagnosed primarily on the basis of abnormal PSA values, and about half were palpable. Preliminary results showed no significant differences in overall or prostate-cancer mortality after 12 years of follow-up, particularly among men with low-risk cancers. 31 In other randomized trials, the combination of external-beam radiotherapy and androgen-deprivation therapy was associated with increased overall and disease-specific survival, as compared with radiotherapy alone in men with intermediate- or high-risk early-stage prostate cancers32,33 and as compared with androgen-deprivation therapy alone in men with locally advanced cancers.34 Data are lacking from randomized trials comparing radiotherapy with either surgery or watchful waiting for early-stage prostate cancer.28
Informed Decision Making
Given the complexity of issues regarding prostate-cancer screening, experts recommend that men receive support in making informed decisions.35,36 However, PSA testing is often performed without discussion of the benefits and harms of screening.37,38 Competing clinical demands and the challenge of providing sufficient information to support decision making present important barriers to having this discussion.39 A strategy for conveying relevant information is to use “decision aids,” defined as interventions that “help individuals make specific and deliberative choices among options . . . by providing . . . information on the options and outcomes relevant to an individual's health status.”35 A meta-analysis of 18 randomized trials of screening decision aids, which included video, written, and Internet-based materials, showed that they significantly increased patients' knowledge and confidence in their screening decisions and also decreased PSA screening.40
Areas of Uncertainty
Men undergoing regular PSA screening are much more likely than unscreened men to receive a diagnosis of prostate cancer. However, a substantial proportion of PSA-detected prostate cancers are considered to be overdiagnosed.23 Although the PSA level, the findings on digital rectal examination, and the Gleason score on biopsy can be used to stratify patients into risk groups, they cannot perfectly predict which cancers are destined to cause future illness. Consequently, the majority of men with an early-stage cancer opt for a potentially curative treatment such as surgery or radiotherapy.41 Biomarkers that may better identify high-risk cancers (and avert unnecessary treatment) are being evaluated,42 including ones targeting hypermethylation and gene expression, but their clinical usefulness is currently unclear.
An alternative approach that is intended to minimize the harms of overdiagnosis is a strategy of active surveillance for men with low-risk cancers (a PSA level of ≤10 ng per milliliter and a Gleason score of ≤6) with the use of serial PSA tests, digital rectal examinations, and prostate biopsies.43 Aggressive treatment is offered only for signs of clinical progression on surveillance testing — although criteria for defining progression remain controversial — or at the patient's request. Pooled results from seven observational studies involving 2130 subjects showed a very low risk of death from prostate cancer (0.3%), with 64% of men who continued to undergo active surveillance rather than receive active treatment throughout a median follow-up period of 43 months.44 The randomized Prostate Testing for Cancer and Treatment trial (NCT00632983) is enrolling 2050 men between the ages of 50 and 69 years who have early-stage prostate cancer and following them at least through 2013 to compare rates of survival and disease progression between active surveillance and aggressive treatment.45
Although screening decision aids are recommended to support informed decision making,35,39 more research is needed to determine the optimal formats, timing, and settings for providing them and their effects on clinical outcomes.
Guidelines
Whereas early American Urological Association and American Cancer Society guidelines strongly supported routine, annual prostate-cancer screening,46,47 subsequent guidelines have taken into account the uncertainties regarding the outcomes of screening. Current American Urological Association and American Cancer Society guidelines, updated after the publication of the results of the ERSPC and PLCO trials, are summarized in Table 2Table 2
Prostate-Cancer Screening Guidelines..11,13 Both organizations encourage shared decision making between patients and clinicians and periodic PSA testing when the patient's life expectancy is at least 10 years. However, guidelines differ with respect to the recommended age at which to begin routinely discussing screening and the criteria for biopsy referral. The American Cancer Society guidelines11 also recognize the challenges in helping men achieve informed decision making and list a number of publicly available written and Web-based screening decision aids.The U.S. Preventive Services Task Force recently issued a draft recommendation against PSA screening for asymptomatic men, regardless of their age, racial or ethnic group, or family history (Table 2).48 The task force concluded that the harms of screening outweigh the benefits. The task force's final recommendation will be released after publication of this article.
Conclusions and Recommendations
Decisions about prostate-cancer screening should be based on the preferences of an informed patient. The man in the vignette should be engaged in a shared decision-making process that elicits his values and preferences for the potential consequences of testing. Supporting his decision making requires informing him of his cancer risk (which is average) and educating him about the often indolent natural history of prostate cancer, the limited accuracy of screening and diagnostic tests, and the potential benefits and harms of screening and treatment. He should be informed that there is inconsistent evidence thus far from the major screening trials regarding whether screening decreases mortality from prostate cancer. Although articles on the initial trial results may have underestimated the potential benefit of screening with respect to prostate-cancer mortality, screening has not been shown to improve survival overall. In addition, the small absolute disease-specific survival benefit must be balanced against the potential harms of overdiagnosis and complications of treatment, including urinary, sexual, and bowel dysfunction. Moreover, the optimal treatment for early-stage cancer, if any, is uncertain. Having the patient review a decision aid (see, for example, www.cdc.gov/cancer/prostate/pdf/prosguide.pdf, or, for black men, www.cdc.gov/cancer/prostate/pdf/aaprosguide.pdf) might facilitate a more efficient and effective discussion that helps him reach his best decision.
The views expressed in this article are those of the author and do not necessarily represent the official positions of the Department of Veterans Affairs.
Dr. Hoffman reports receiving payment for providing expert testimony regarding prostate-cancer screening and partial salary support for medical editing from the Foundation for Informed Medical Decision Making, a not-for-profit 501(c)(3) private foundation that develops content for patient-education programs (including programs on prostate-cancer screening and treatment) and having an arrangement to produce these programs with a for-profit company, Health Dialog. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the author are available at NEJM.org.
This article (10.1056/NEJMcp1103642) was published on October 26, 2011, at NEJM.org.
An audio version of this article is available at NEJM.org.
I thank Drs. Michael Barry and David Penson for their helpful comments on an earlier draft of the manuscript.
Source Information
From the Departments of Medicine and Family and Community Medicine, University of New Mexico School of Medicine, and the Medicine Service, New Mexico Veterans Affairs Health Care System — both in Albuquerque.
Address reprint requests to Dr. Hoffman at 1501 San Pedro Dr. SE, Mailstop 111, Albuquerque, NM 87108, or at rhoffman@unm.edu.
Key Clinical Points
PROSTATE-CANCER SCREENING
• The introduction of prostate-specific antigen (PSA) testing has nearly doubled the lifetime risk of receiving a diagnosis of prostate cancer.
• A substantial proportion of PSA-detected cancers are considered overdiagnosed because they would not cause clinical problems during a man's lifetime.
• Early results from two large, randomized, controlled trials of screening were inconsistent; a European study showed a modest decrease in prostate-cancer mortality, whereas a U.S. study showed no decrease in prostate-cancer mortality.
• Treatments for prostate cancer can lead to complications, including urinary, sexual, and bowel dysfunction.
• Men considering prostate-cancer screening should be informed about the potential benefits and harms of screening and treatment.
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- Comments (48)
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48 Reader's Comments
JEANNE LENZER | Other | Disclosure: NoneKINGSTON NYNovember 27, 2011Poll query linked to article improperly framed
As a journalist, I've found that many providers who believe the USPSTF Grade D recommendation, also believe in initiating a discussion with the patient by explaining the controversy, the reasons for the Grade D recommendation, and letting them decide based on that information. By shoehorning every provider who agrees with the Grade D recommendation into an option that states they would not initiate a conversation with the patient (according to the 3 poll options), NEJM introduces an element of bias, potentially forcing some providers to check off option B (support Grade C recommendation and initiate a conversation).
Ferdinand Frauscher | Physician | Disclosure: NoneAustriaNovember 27, 2011Do we need imaging for successful prostate cancer screening?
One of the major problems I see in the discussion to screen or not for prostate cancer, is the lack of an imaging method, which allows for detection, localisation and size and number of prostate cancer lesions. In Innsbruck we have already introduced PSA screening in 1988. The acceptance of PSA testing was good, however the approach when PSA is elevated, the next step is systematic biopsy has shown to be not effective. Systematic biopsy is an old technique with a lot of disadvantages including inaccuracy, invasiveness and no detailed information about the cancer size. Furthermore systematic biopsy has shown often to result in undergrading of prostate cancer, which may result in inadequate therapy. New imaging techniques - including contrast-enhanced US and sono-elastography - have shown the potential to detect cancer. Furthermore multiparametric MRI is also useful. In addition the combined use of US and MRI with new imaging fusion techniques is promising. Therefore I believe that imaging will play a major role in prostate cancer screening, since the current data show that imaging may allow for diagnosis of "relevant cancers", where therapy will improve patient survival.
WILLIAM FULLER | Student | Disclosure: NoneBROOKLYN NYNovember 27, 2011Missing the Point
I am disheartened by several of the comments on this page that seem to miss a main point of the discussion. Even if we grant that there is some small absolute prostate cancer-specific mortality reduction associated with PSA screening, what is the cost, both financial and in terms of personal harm, associated with one death prevented by PSA screening? Those on this forum having undergone prostate biopsy will agree that it was a painful procedure, and the costs associated with it and its complications are high. How many patients will undergo this hardship and possibly suffer lasting harm in the hopes of preventing a disease that their PSA, due to its lack of specificity, does not reliably indicate that they have?
The question is not whether PSA might find cancer, but whether ordering it will be in the interests of an individual patient. If we refuse to believe the results of two controlled trials indicating that it truly isn't, we have given up any pretense of practicing evidence-based medicine. In short, just because it is the best test we have does not mean it's a good test, or that it should be used in a screening capacity for patients without a history of prostate cancer.IAN HOLLIDAY | Other | Disclosure: NoneGRAVESEND United KingdomNovember 24, 2011A question of values?
Although a professional, I have read these comments as a patient looking for some facts before opting for biopsy following a superb PSA velocity which should be studied. Interesting as it is that the "ding dongs" a someone calls us, are arguing about research limitations and findings but there are several anecdotes of patients who are now alive because of screening, whether via DRE, PSA or biopsy. In the face of those anecdotes, I find myself saying "Regardless of the statistics, here are people - able to speak because of life saving intervention. OK, only a few but, I am minded to say I'd like to be one of those whose life is extended and who can continue to read this web site for a few more years." Maybe I am wrong but, then again, those of you who advocate patient discussion might glean something from my, maybe twisted, mind set. Alternatively, maybe someone should do some decent research on why patients have trouble deciding, rather than, again, anecdotal stuff.? Dr Siguel above seems to be the only one making sense to me, as a patient, when he says that patients need more data and more depth.
Timothy Dayton | Other | Disclosure: NoneNovember 24, 2011PSA Testing
The PSA testing I had done over a number years showed a gradual rise in the last 3 years until it reached > 4.0. At that point I did not have any symptom detectable by DRE. I decided to have a biopsy and was presented with cancer in several pin samples with a Gleason of 6 or 7. I decided to have surgery, I was 55. I had successful surgery and post operative testing showed a Gleason 7 and a relatively aggressive sort of cancer. I am very glad I did what I did and I am satisfied with the results so far. Had I not had the testing I am not sure how long it would have been to have a DRE indicate a problem and then what would be my choices several years further into cancer growth. Until there is a better test the PSA is the best we have even if it isn't perfect. Early detection permitted prostate removal with wide margins and with the use of nerve sparing surgery. I have had excellent results and am not worried about this problem anymore. I do get a PSA test every 6 months just to make sure it hasn't spread.
HENRY FOURCADE, MD | Physician | Disclosure: NoneBlaine WANovember 23, 2011Retired Anesthesiologist
My father had annual H&P's and was in good health until his first PSA test result returned at 79. He had external beam radiation for invasive prostate cancer followed by a complicated medical course. I would like to continue my annual PSAs & DRE, and know when my PSA is rising before it hits 79. Is someone in this free country going to tell me that is unethical?
MR ERNEST KRAUS, RPH | Other | Disclosure: NoneWOODBURY NJNovember 23, 2011My PSA <4.0
I too had increasing PSA's but never hit that magic .4.0. Digital exam found no enlargement, firmness and a small nodule. My urologist scheduled me for a biopsy with the comment " I'm sure it will be negative, but let's be sure." An evening phone call from him said that 12 of 16 biopsies were positive with Gleasons og 6/7. I opted for surgery with continuing PSA follow up. Some years later, the PSA went from <0.01 to detectable levels. Consultation with both my surgeon and the radiation oncologist came up with a diagnosis of recurence. I also found out that I'm part of the 35% that do reoccur. I opted for XRT and continue to monitor PSA. I can only speculate what would have happened had I not had the surgery; would I still be alive? Would I have mets? No one knows. I don't care about the studies, the statistics, the cost. To me, it was worth it.
JAI JOSHI, MD | Physician | Disclosure: NoneLAREDO TXNovember 23, 2011Answer to Poll Question
The four articles in this issue illustrate, there is no right answer to the poll question. The seemingly easy answer is that you initiate a discussion, but that’s the wrong choice.
john williams | Other | Disclosure: NoneNovember 23, 2011PSA alternatives
I keep waiting for the medical "experts"to tell me what alternative tests are available for determining the presense of prostate cancer?????
GIOVANNI SALAMANO, MD | Physician - Endocrinology | Disclosure: NoneVERCELLI ItalyNovember 06, 2011Prostatic cancer screening: what is the most useful screening procedure?
The hypothesis that the pathogenesis of prostatic cancer is linked to an inflammatory process seems sufficiently demonstrated by both hystological and clinical evidences supporting the presence of a precancerous lesion called "Proliferative inflammatory atrophy."
Molecular genetic supports this idea demonstrating that hypermethylation of CpG island of Gluthatione Methyl Transferase (GTP1) gene, on chromosome 11q13, is the cause of reduced transcriptional and antioxidant activity of this enzyme, causing an increased genomic instability at prostatic epithelial basal cells.
The "gatekeeper" gene for "prostatic intraepithelial neoplasia" development is NKX3.1, located on chromosome 8p21, encoding a prostatic specific homeobox gene, essential for normal prostate development, inactive in cancer, and able to repress the expression of Prostatic Specific Antigen (PSA).
PSA, also called Kallicrein 3, is itself a protein involved into inflammatory processes, present at increasing concentrations during prostatitis.
Bearing these pathogenetic considerations in mind, the measurement of PSA total, free, velocity and density for screening pourpose is unjustified in otherwise healthy patients.john williams | Other | Disclosure: NoneNovember 05, 2011PSA tests
My prostate cancer was diagnosed indirectlly through a PSA test >4 followed by a free PSA and a biopsy. It was very localized but a gleeson 9. What alternative do you ding dongs have to offer in lieu af a PSA test( the DRE was clear so you can't use that answer!!!)?
SERGIO STAGNARO, MD | Physician | Disclosure: NoneRIVA TRIGOSO ItalyNovember 05, 2011PSA Evaluation only in presence of Protate Oncological Inherited Real Risk.
To ascertain PSA in all men, without knowing prostate cancer Inherited Real Risk, is neither scientific nor useful.
MR EDWARD JAGO | Other | Disclosure: NoneDUBLIN OHNovember 04, 2011Just a survivor's comment
It was suggested that I have a PSA test by my physician some years ago. The test showed a very small level. The test was repeated first at two year intervals and than at one year intevals over a period of about 10 years. My physician plotted the data each year on a time line and we watched first a steady very low increase then an accelerating rate until the last increase showed about a thirty % increase. At that point a biopsy indicated a cancer. I elected surgery and the prostate was removed and the margin cleared. I elected no further treatment be performed. Continued PSA monitoring for the last 12 years has shown no significant PSA so I consider my self prostate cancer free. So I say montitor and watch the trend liine.
MR MARIO GUARNIERI | Other | Disclosure: NonePRATO ItalyNovember 04, 2011PSA Screening does help ....
Understand that more prostate volume and more inflammation gets more PSA . However PSA high value does not mean a prostate cancer. There is a helpful new blood test being done in Milan and Firenze, Italy and named P.H.I. (Prostate Health Index) which in my case and others did indicate high-risk of cancer, proven by biopsy. I had surgery on August 31 and am feeling good. PSA will help again this month for deciding whether radiotherapy applications may be advisable or not.
NORMAN SOLOMON, MD | Physician | Disclosure: NoneLOS ANGELES CANovember 04, 2011Advice On Counseling
The dilemma is clear and has been for years. All the anxious waiting for these studies to help clarify what to do have not really changed much. You can explain this to patients till you're blue in face or give them handouts, and they still ask you the same questions. The bottom line is what psychological burdens an individual patient can handle. If learning that ten years from now, they have prostate cancer and if they had only had a psa, maybe things would have been better is something they couldn't handle, then PSA screening is right for them. If they have a poor tolerance for making difficult decisions and would have difficulty knowing that they have a "cancer," but that they are just watching it, then PSA testing would probably be the wrong choice for them. The decision has more to do with what they can handle than it has to do all the facts we bombard them with. I've yet to have a patient NOT ask me at the end of my discussion, what would you do, which shows you their inability in many cases to process the information in a manner that is best suited for themselves.
Jim Thayer | Other | Disclosure: NoneNovember 03, 2011Missing a most relevant issue
As a researcher supporting the medical and pharmaceutical industry, and a prostate cancer (PC) survivor, I am appalled that so much effort is applied to this issue without considering the most obvious benefit of REPEATED PSA testing. While I did not know that my grandfather had died from metastasized PC until after I had been diagnosed, I had my PSA tested periodically (2-3 year intervals). It was fairly consistent until last year when it increased by several fold (over a 3-year period). I had the biopsy and discovered the PC in time to take action.
While a single PSA test may not be very instructive for all the reasons listed by others, periodic PSA tests are very helpful as they establish a baseline for subsequent comparisons. Because of the current controversy, my physician did not intend to perform the PSA test during my last physical, but I insisted. In my case, it probably saved my life. To me, all this controversy over the value of the PSA test seems ridiculous without consideration of repeated tests to establish a baseline, perhaps best initiated during the age of 45-50.HANS-HERMANN DUBBEN | Other | Disclosure: NoneHamburg GermanyNovember 03, 2011Prostate cancer screening: A controversy about random numbers
Studies on prostate cancer screening are principally not qualified to provide scientifically valid information about a benefit in terms of (cancer specific) mortality. Such trials have too low statistical power because of low cancer-specific mortality combined with long history of disease, lack of compliance, contamination, and unclear causes of death. Trials with sufficient power require millions of participants and tolerate no loss from follow up. Their results become available only decades after trial initiation. Then they are necessarily antiquated due to changes of the population, treatment options and diagnostics. Indispensible prerequisites of science are testable hypotheses and replicability. Neither is a given for early detection of (prostate) cancer. Underpowered studies simply generate random numbers. Thus it is not surprising that the results of the ERSPC and PLCO study are contradictory. Alone the disadvantages are evident because the number of overtreatments are much higher than the number of allegedly prevented PCa-deaths.
Cancer screening studies appear unethical and contradict §17 of the Declaration of Helsinki.John Costello | Physician | Disclosure: NoneNovember 02, 2011Internist
The US Task Force stance is correct, but - it changes nothing . The trial in the US may be too compromised to prove the value , and the European trial suggest- with varying criteria for entry, and followup- that screening helps about 1 in 1, 000 or so /year- about the same as mammography, for those likely to live 10 years , between 50 and 65 -70. It's still up to the individual to decide, with the help of a physician/family / friend what is best for them, based on imperfect data. The larger ? is -should a health system pay for such screening?
CHUAN PHING TANG, MD | Physician - Dermatology | Disclosure: NoneSITIAWAN MalaysiaNovember 02, 2011Find a better treatment
It is agreeable that DRE with PSA screening if done properly will help to pick up early prostate cancer with better accuracy coupled with TRUS biopsy. It is the treatment options to the patient and its complications that put off the patients. PSA screening itself is not a big issue. It is time for the urologist to find a better and less invasive way of diagnosing and treating the Ca prostate. Man is worried of ED,incontinence,retrograde ejaculation... Man wants better quality of life.
JEFFREY HOROWITZ, MD | Physician | Disclosure: NoneFALL RIVER MAOctober 30, 2011What is the code for "PSA discussion with patient"?
I can't help thinking about where are we going to find the extra 10-15 minutes to properly discuss the option of PSA screening with our patients. It seems impossible to tack that on to a routine office visit, do a good job and not feel rushed and fall behind schedule all day. Realistically, forget it unless there is a code for it!
GEORGE ADAMS, MD | Physician | Disclosure: NoneOctober 29, 2011Whenever You Like
It's not yet illegal to check your PSA. I check mine q6 months as that's what Im confortable with. So do what you're comfortable with. Check it whenever you like. You will be as right as anyone else as the final answers are not in and may never be. When it becomes illegal to check it frequently in the US go to Costa Rica on vacation and check it there.
EDUARDO SIGUEL, MD | Physician | Disclosure: NoneGAITHERSBURG MDOctober 29, 2011Need Better data, not longer philosophical decisions
Change research and data to offer better data on choices. Build mathematical models probability distributions of types of cancer and treatment outcomes given values of variables such as age, weight, race, nutrient status (such as Vit D and essential fats), family history, prostate size, rate of increase of PSA, treatment type, etc. And chart probability distributions and changes in PSA as a function of biological variability, exercise, lab variability, diet, weight, etc. Develop accurate models of the causes of prostate cancer, the factors that increase or decrease cancer rates. This is feasible today. Instead, we spend millions on useless clinical trials. Current financial incentives discourage better mathematical/biophysical/biological models.
When the data become available, the optimal decisions will usually be obvious. Now, with ignorance, with poorly designed clinical trials, with focus on profits, we don't have data to make optimal decisions and we must obfuscate recommendations.CLYDE SCHECHTER, MD | Physician | Disclosure: NoneCYPRESS CAOctober 28, 2011The PSA Dilemma -- A Result of Entrepreneurial Medicine
So the major trials were seriously flawed. Those in the US suffered from severe contamination in the control group, and screening prior to randomization. Why is that? Because PSA screening was so deeply entrenched in medical practice before it was ever subjected to serious testing. This is typical of entrepreneurial systems: products and services are launched, marketed, and hyped before anyone has time to figure out if they are any good. When it's ordinary consumer goods, probably that doesn't matter much. But here we see that the US undertook a mass campaign of genital mutilation for decades, and the practice became so widespread that it was impossible to mount a valid study of whether we had anything good to show for it. We still don't know if even a single life was saved, and we never will.
The late Thomas Chalmers used to say "Randomize the first patient." His dictum, still ignored, is the wisest advice I have ever heard from any health professional.James Mohler | Physician | Disclosure: NoneOctober 28, 2011Clarification on development of the PSA test
While Dr. Ablin did discover a "prostate-specific antigen" that is confined to the normal prostate, he neither developed the PSA test nor discovered the PSA on which the current test is based. That credit goes to Roswell Park Cancer Institute researcher T. Ming Chu, PhD, DSc, and his colleagues, who identified and purified PSA and later developed the simple PSA blood test that is used today for the early detection and management of prostate cancer. The team published its first major paper in 1979 in Investigative Urology, and in 1984, a patent was issued to New York and RPCI and the technology was transferred to the biomedical industry for preparing test kits. The PSA test received FDA approval in 1986 as a monitor for treatment response and disease recurrence and in 1994 as a screening tool for diagnosis. Dr. Chu received the Presidential Award from the AUA in 1993 and was featured in the April 1998 issue of Cancer Research for his research on the use of tumor cell products in the diagnosis and treatment of cancer and for his leadership role in the discovery of PSA and development of the PSA test.
Missing the point
Just getting your prostate cancer diagnosed does not mean a doctor has saved your life, or even given you longer to live. The science in the studies simply has not shown that to be true. I am pleased that those who have had a diagnosis are glad they went through the ordeal and feel it has made a difference for them, but I worry when they go around preaching that their life has been saved by having a PSA and getting their colleagues to get one too.
So what are the alternatives to PSA you all ask?
Get on with life, spend less time in a doctor's room and more time walking and enjoying life, and if you get symptoms, go and see a doctor. You will live just as long and perhaps with all that extra exercise a little bit more.