Sessile serrated adenomas: high-risk lesions?


Sessile serrated adenomas (SSAs) were unrecognized in pathology and gastroenterology practice until about 2005; we have diagnosed them since 2001, allowing up to 10 years of follow-up. We evaluated follow-up of patients with sessile serrated adenoma diagnosed between 2002 and 2004 in our teaching institution and compared it to follow-up of randomly selected tubular adenomas. Materials from patients diagnosed with sessile serrated adenoma from January 2002 to December 2004 were reviewed. A control group of patients with sporadic tubular adenomas was selected. Ninety-nine sessile serrated adenomas from 93 patients were diagnosed between January 2002 and December 2004. Forty three patients (46.2%) had follow-up colonoscopy. One or more lesions were found in 42 (97.6%) of 43 patients. Mucinous adenocarcinoma was diagnosed in 1 (2.3%) of 43 patients, and 1 (2.3%) of 43 patients had high-grade dysplasia in an sessile serrated adenoma. Sessile serrated adenomas were found in 22 (51.2%) of 43 patients, 16 (37.2%) of 43 patients had tubular adenomas, and hyperplastic polyps were diagnosed in 18 (41.9%) of 43. Ninety-two patients with tubular adenomas between January 2002 and December 2004 formed the control group. Sixty-six patients (71.7%) received follow-up colonoscopy. Most (53/66, 80.3%) patients had tubular adenomas on follow-up, 12 (18.2%) of 66 patients had hyperplastic polyps, and 2 (3.0%) of 66 patients had a sessile serrated adenoma. The follow-up of sessile serrated adenomas from the study period (2002 to 2004) was more rigorous than proposed for sporadic tubular adenomas (patients with sporadic tubular adenomas were also followed up more aggressively than suggested by guidelines). Those with follow-up were managed as per advanced adenomas; their clinical outcomes supported this. These results suggest that guidelines for following up patients with sessile serrated adenomas as per advanced adenomas are warranted.

Source: Science Direct.

 

 

CEA and long-term follow-up of mucinous pancreatic cysts including intraductal papillary mucinous neoplasm.


The utility of Carcino Embryonic Antigen (CEA) in differentiating malignant from benign pancreatic cysts is controversial. We sought to examine the role of CEA in differentiating benign from malignant cysts and its utility in progression of cyst size in follow-up.

Methods

Retrospective chart review of patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration for mucinous cysts between 1998 and 2010. CEA was measured in benign and malignant mucinous cysts. Coefficient of determination (R2) was used to measure the association between change in cyst size and CEA. Mann–Whitney test was used to compare the median values of CEA.

Results

143 patients (38.4% males) were included (mean age 68.9 ± 0.8 years). 105 patients had intra-cystic CEA measured. 63 patients underwent surgery while 80 patients were in the follow-up group. In the surgical group, median CEA value for benign and malignant mucinous neoplasms was 796 and 438 ng/ml, respectively (p = 0.79). The median follow-up was 21 months. There was no correlation between CEA level and progression in cyst size in patients who had >6 months of follow-up, R2 = 0.0002. Malignant transformation was observed in 5 (5.9%) patients.

Conclusion

CEA level was not predictive of malignant cyst nor cyst size progression over follow-up.

Source: Science Direct.

 

A Combination of Esomeprazole and Aspirin Reduce Tissue Concentrations of Prostaglandin E2 in Patients with Barrett’s Esophagus.


Proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett’s esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled phase II trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin E2 (PGE2) in patients with BE with no dysplasia or low-grade dysplasia.

Methods

Participants were recruited through the multi-center Cancer Prevention Network and randomly assigned to groups that were given esomeprazole (40 mg, twice daily) in combination with an aspirin placebo (once daily) (Arm A; n=42), with 81 mg aspirin (once daily) (Arm B; n=63), or with 325 mg aspirin (once daily) (Arm C; n=63) for 28 days. We collected esophageal biopsies before and after the intervention period, to determine the absolute change in mean concentrations of PGE2 (the primary endpoint).

Results

Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentrations of PGE2 was reduced by 67.6±229.68 pg/mL in Arm A, was reduced by 123.9±284.0 pg/mL in Arm B (P=.10 vs Arm A), and was reduced by 174.9 ±263.62 pg/mL in Arm C (P=.02 vs Arm A).

Conclusions

In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients.

Source: Science Direct.

 

Keywords

  • esophageal cancer;
  • NSAIDs;
  • inflammation;
  • esophagus

 

Hepatobiliary disorders among naïve patients with ulcerative colitis in Upper Egypt.


Association of ulcerative colitis (UC) with hepatobiliary disorders is well recognised. The most common hepatobiliary complications of inflammatory bowel disease (IBD) are fatty liver infiltration and cholelithiasis. The prevalence of liver dysfunction in IBD remains unclear. The aim of the study is to try to identify the frequency and risk factors of hepatobiliary disorders among patients with UC in Upper Egypt.

Patients and methods

We prospectively analysed 33 patients with newly diagnosed UC of Tropical Medicine and Gastroenterology Department, Assiut University Hospital. For all participants, the following were conducted: clinical evaluation, abdominal ultrasonography (US) examination and laboratory investigations. Risk factors of hepatobiliary disorders were identified using univariate, then multivariate analysis.

Results

The frequency of hepatic disorders (fatty liver and elevated liver chemistry) was 75.8% in study patients while the frequency of biliary disorders (gallbladder stones and gallbladder wall thickening) was 54.5%. A higher risk of hepatic disorders was observed with older age (odds ratio (OR) 14, 95% confidence interval (CI) 2–124). A higher risk of biliary disorders was observed with UC severe activity index (OR 27, 95% CI 3–292).

Conclusions

The frequency of hepatobiliary disorders in patients with UC exceeded what was previously reported. High frequency of hepatic disorders was related to older age, while that of biliary disorders was related to UC activity.

Source: Science Direct.

 

Neuroendocrine regulation of rearing behavior in the native Thai hen.


Vasoactive intestinal peptide (VIP) is the avian prolactin releasing factor and changes in the concentrations of plasma prolactin (PRL) are found during the avian reproductive cycle. This study investigated the changes in the VIP/PRL system of native Thai hens rearing their young as compared to hens deprived of rearing their chicks. The number of VIP-immunoreactive (VIP-ir) neurons in the Nucleus inferioris hypothalami (IH) and Nucleus infundibuli hypothalami (IN) of hens rearing chicks (R) were compared with those of non-rearing chicks (NR). Plasma PRL levels were determined by enzyme-linked immunosorbent assay. The localization and number of VIP-ir neurons were determined by immunohistochemistry. The numbers of VIP-ir neurons in the IH–IN areas were high in the R hens, whereas the number of VIP-ir neurons decreased in the NR hens as compared to their respective R hens. During the rearing period, changes in the VIP-ir neurons within the IH–IN were correlated with plasma PRL levels. The results of the present study indicate for the first time that the VIP/PRL system plays a role in neuroendocrine reorganization to establish maternal behavior in native Thai chickens. The VIP/PRL system functions not only as a well established key regulator of incubation behavior, but is also involved in the regulation of rearing behavior. It is possible that VIP and the decline in the number of VIP-ir neurons and in turn VIPergic activity and the decrease in PRL levels are related to their contribution to rearing behavior of this non-seasonal breeding, equatorial precocial species.

Source: Science Direct.

 

The USPSTF Recommendation on PSA Screening: Our Readers Have Spoken.


Results of an online poll and reader feedback about prostate-specific antigen screening.

After the U.S. Preventive Services Task Force (USPSTF) published its final recommendation opposing prostate-specific antigen (PSA) screening, we conducted an online poll of readers’ reactions. A total of 177 readers responded to the question “Please choose the statement that best fits your reaction to the USPSTF recommendation against PSA screening.”

As shown in the table, 78% of respondents agreed with the USPSTF recommendation, but a substantial proportion still will offer screening selectively. I’m guessing — based on informal discussions with other physicians — that some of these responses reflect concerns about litigation for failure to diagnose cancer.

Many readers shared their perspectives by posting “reader remarks” in response to our recent summary of the USPSTF recommendation (JW Gen Med Jun 7 2012). One reader will continue to screen because she “has probably saved the life” of several men with screening. She might be right: Even skeptics must concede that individual lives occasionally are saved by screening. After all, if enough men undergo prostatectomy, somewhere in the mix are men who eventually would have died of prostate cancer. But, the important question is this: How many people must undergo screening, biopsies, prostatectomies, and radiation therapy to benefit one person? The Task Force concluded that the number needed to screen (NNS) and number needed to treat (NNT) are too high and result in adverse outcomes for too many people, whereas advocates of screening believe otherwise. Nothing is wrong with arguing that a particular NNS or NNT is too high, as long as we remember that selection of “appropriate” cutoffs are value judgments and not scientific truths.

Another reader entitled his remark “Can’t tell who is saved.” He correctly implies that when a man survives (cancer-free) after treatment for PSA-detected cancer, we can’t determine whether his particular life was saved by screening. From the European randomized screening trial (JW Gen Med Mar 14 2012), we can infer that roughly 1 of every 30 patients who received treatment for screening-detected cancer had his life extended, but we don’t know which particular man was “saved” and which 29 underwent treatment unnecessarily.

Several respondents claimed that mismanagement of PSA results and overtreatment of patients with low-risk prostate cancer — and not PSA screening — are the real problems. In my view, both the PSA test and overtreatment are problematic. No screening test has perfect sensitivity and specificity, but PSA test accuracy is especially poor: Fully 25% of men with PSA levels between 2 and 4 ng/mL have prostate cancer (JW Gen Med Jun 8 2004), and many men with PSA levels between 4 and 10 ng/mL don’t have prostate cancer. Sensitivity and specificity can be refined somewhat by using age-specific cutoffs, change in PSA level over time, or other variations; but so far, these other approaches have not been tested rigorously in controlled studies. Management approaches are all over the map because clinicians don’t quite know what to do when PSA levels go up a little: Biopsy now? Repeat in 1 year? Repeat in 6 months? Give antibiotics for “prostatitis,” and repeat in 1 month? And, regarding overtreatment of men with low-risk cancer, thoughtful urologists have told me, “I agree that we overtreat. But if a patient who doesn’t really need surgery says, ‘I want my cancer treated,’ what are we supposed to do? If we don’t do the surgery, he’ll go elsewhere.”

Another reader suggested that PSA screening is most beneficial in men older than 75. However, in the European screening trial, among men 70 or older at the time of randomization, researchers noted a trend toward higher mortality in screened versus nonscreened men. And, in the largest treatment trial (prostatectomy vs. watchful waiting in men with localized cancer; JW Gen Med Sep 16 2008), prostatectomy was associated with lower mortality only in men younger than 65.

One final interesting comment: A physician reader notes that when patients ask him whether he gets PSA tests himself, he replies that he does not, even though “my father and father-in-law had prostate cancer.” In some clinical encounters, it might be appropriate to share one’s personal medical decisions. But, I believe that when patients ask about PSA testing, physicians should explain why they agree or disagree with screening and leave their own healthcare decisions out of the discussion.

Source: Journal Watch General Medicine

 

Intermittent oral iron supplementation during pregnancy.


Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus.Traditionally, gestational anaemia has been prevented with the provision of daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation.

Objectives

To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012).

Selection criteria

Randomised or quasi-randomised trials.

Data collection and analysis

We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy.

Main results

This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation.

Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed and most had high levels of attrition. Overall, there was no clear evidence of differences between groups for infant primary outcomes: low birthweight (average risk ratio (RR) 0.96; 95% confidence interval (CI) 0.61 to 1.52, seven studies), infant birthweight (mean difference MD -8.62 g; 95% CI -52.76 g to 35.52 g, eight studies), premature birth (average RR 1.82; 95% CI 0.75 to 4.40, four studies). None of the studies reported neonatal deaths or congenital anomalies.

For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80, four studies) and women receiving intermittent supplementation had less side effects (average RR 0.56; 95% CI 0.37 to 0.84, 11 studies) than those receiving daily supplements. Women receiving intermittent supplements were also at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.48; 95% CI 0.35 to 0.67, 13 studies). There were no significant differences in iron-deficiency anaemia between women receiving intermittent or daily iron+folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63, 1 study). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy.

Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women’s anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on the results of the review.

Authors’ conclusions

The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.

 

Plain language summary

Intermittent regimens of iron supplementation during pregnancy

Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs. Traditionally, pregnancy anaemia has been prevented with the provision of daily iron supplements, however, it has recently been proposed that if women take supplements less often, such as once or twice weekly rather than daily, this might reduce side effects and increase acceptance and adherence to supplementation. In this review we assess the benefits and harms of intermittent (i.e. one, two or three times a week on non-consecutive days) oral supplementation with iron or iron+folic acid or iron+vitamins and minerals for pregnant women.

We included 21 randomised controlled trials, but only 18 trials involving 4072 women, had information on the outcomes we evaluated. Three studies looked at intermittent iron alone versus daily iron alone; there did not appear to be differences in the effects of two types of regimens when women were followed up.The other studies included in the review compared intermittent iron+folic acid versus daily iron+folic acid. Two of these studies looked at intermittent versus daily iron+folic acid in women who were also advised to take daily calcium supplements.There was no clear evidence of differences between groups for most of the outcomes we examined including infant birthweight, premature birth, perinatal death, and anaemia, haemoglobin concentration and iron deficiency in women at the end of pregnancy. However, women receiving intermittent rather than daily iron supplements were less likely to report side effects (such as constipation and nausea). In addition, intermittent supplementation appeared to decrease the number of women with high haemoglobin concentrations during mid and late pregnancy compared with daily regimens. High haemoglobin concentrations may be harmful as they may be associated with an increased risk of having a premature birth and low birthweight baby. There were no other clear differences between groups for other outcomes examined.

Source: Cochrane Library.

 

 

Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals.


More than 30 years into the global HIV/AIDS epidemic, infection rates remain alarmingly high, with over 2.7 million people becoming infected every year. There is a need for HIV prevention strategies that are more effective. Oral antiretroviral pre-exposure prophylaxis (PrEP) in high-risk individuals may be a reliable tool in preventing the transmission of HIV.

Objectives

To evaluate the effects of oral antiretroviral chemoprophylaxis in preventing HIV infection in HIV-uninfected high-risk individuals.

Search methods

We revised the search strategy from the previous version of the review and conducted an updated search of MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in April 2012. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing trials.

Selection criteria

Randomised controlled trials that evaluated the effects of any antiretroviral agent or combination of antiretroviral agents in preventing HIV infection in high-risk individuals

Data collection and analysis

Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors using a standardized data extraction form. Relative risk with a 95% confidence interval (CI) was used as the measure of effect.

Main results

We identified 12 randomised controlled trials that meet the criteria for the review. Six were ongoing trials, four had been completed and two had been terminated early. Six studies with a total of 9849 participants provided data for this review. The trials evaluated the following: daily oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms: TDF, TDF-FTC and placebo arm. The studies were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, serodiscordant couples and other high risk men and women.

Overall results from the four trials that compared TDF-FTC versus placebo showed a reduction in the risk of acquiring HIV infection (RR 0.51; 95% CI 0.30 to 0.86; 8918 participants). Similarly, the overall results of the studies that compared TDF only versus placebo showed a significant reduction in the risk of acquiring HIV infection (RR 0.38; 95% CI 0.23 to 0.63, 4027 participants). There were no significant differences in the risk of adverse events across all the studies that reported on adverse events. Also, adherence and sexual behaviours were similar in both the intervention and control groups.

Authors’ conclusions

Finding from this review suggests that pre-exposure prophylaxis with TDF alone or TDF-FTC reduces the risk of acquiring HIV in high-risk individuals including people in serodiscordant relationships, men who have sex with men and other high risk men and women.

 

Plain language summary

Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals

This review evaluated the effects of giving people at high risk for HIV infection drugs to prevent infection (called antiretroviral pre-exposure prophylaxis, or PrEP). We found six randomised controlled trials that assessed the effects of oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo, and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms (TDF, TDF-FTC and placebo arm). The trials were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, people in serodiscordant sexual relationships where one partner is infected and the other is not, and other high risk men and women. The findings suggests that the use of TDF alone or TDF+FTC reduces the risk of becoming infected with HIV. However, further studies are need to evaluate the method of administration (daily versus intermittent dosing), long-term safety and cost effectiveness of PrEP in different risk groups and settings.

Source: Cochrane Library.

 

Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer.


Vascular-endothelial-growth-factor (VEGF) is a key mediator of angiogenesis. VEGF-targeting therapies have shown significant benefits and been successfully integrated in routine clinical practice for other types of cancer, such as metastatic colorectal cancer. By contrast, individual trial results in metastatic breast cancer (MBC) are highly variable and their value is controversial.

Objectives

To evaluate the benefits (in progression-free survival (PFS) and overall survival (OS)) and harms (toxicity) of VEGF-targeting therapies in patients with hormone-refractory or hormone-receptor negative metastatic breast cancer.

Search methods

Searches of CENTRAL, MEDLINE, EMBASE, the Cochrane Breast Cancer Group’s Specialised Register, registers of ongoing trials and proceedings of conferences were conducted in January and September 2011, starting in 2000. Reference lists were scanned and members of the Cochrane Breast Cancer Group, experts and manufacturers of relevant drug were contacted to obtain further information. No language restrictions were applied.

Selection criteria

Randomised controlled trials (RCTs) to evaluate treatment benefit and non-randomised studies in the routine oncology practice setting to evaluate treatment harms.

Data collection and analysis

We performed data collection and analysis according to the published protocol. Individual patient data was sought but not provided. Therefore, the meta-analysis had to be based on published data. Summary statistics for the primary endpoint (PFS) were hazard ratios (HRs).

Main results

We identified seven RCTs, one register, and five ongoing trials from a total of 347 references. The published trials for VEGF-targeting drugs in MBC were limited to bevacizumab. Four trials, including a total of 2886 patients, were available for the comparison of first-line chemotherapy, with versus without bevacizumab. PFS (HR 0.67; 95% confidence interval (CI) 0.61 to 0.73) and response rate were significantly better for patients treated with bevacizumab, with moderate heterogeneity regarding the magnitude of the effect on PFS. For second-line chemotherapy, a smaller, but still significant benefit in terms of PFS could be demonstrated for patients treated with bevacizumab (HR 0.85; 95% CI 0.73 to 0.98), as well as a benefit in tumour response. However, OS did not differ significantly, neither in first- (HR 0.93; 95% CI 0.84 to 1.04), nor second-line therapy (HR 0.98; 95% CI 0.83 to 1.16). Quality of life (QoL) was evaluated in four trials but results were published for only two of these with no relevant impact. Subgroup analysis stated a significant greater benefit for patients with previous (taxane) chemotherapy and patients with hormone-receptor negative status. Regarding toxicity, data from RCTs and registry data were consistent and in line with the known toxicity profile of bevacizumab. While significantly higher rates of adverse events (AEs) grade III/IV (odds ratio (OR) 1.77; 95% CI 1.44 to 2.18) and serious adverse events (SAEs) (OR 1.41; 95% CI 1.13 to 1.75) were observed in patients treated with bevacizumab, rates of treatment-related deaths were lower in patients treated with bevacizumab (OR 0.60; 95% CI 0.36 to 0.99).

Authors’ conclusions

The overall patient benefit from adding bevacizumab to first- and second-line chemotherapy in metastatic breast cancer can at best be considered as modest. It is dependent on the type of chemotherapy used and limited to a prolongation of PFS and response rates in both first- and second-line therapy, both surrogate parameters. In contrast, bevacizumab has no significant impact on the patient-related secondary outcomes of OS or QoL, which indicate a direct patient benefit. For this reason, the clinical value of bevacizumab for metastatic breast cancer remains controversial.

Source: Cochrane Library.

 

The USPSTF Recommendation on PSA Screening: Our Readers Have Spoken.


Results of an online poll and reader feedback about prostate-specific antigen screening.

After the U.S. Preventive Services Task Force (USPSTF) published its final recommendation opposing prostate-specific antigen (PSA) screening, we conducted an online poll of readers’ reactions. A total of 177 readers responded to the question “Please choose the statement that best fits your reaction to the USPSTF recommendation against PSA screening.”

As shown in the table, 78% of respondents agreed with the USPSTF recommendation, but a substantial proportion still will offer screening selectively. I’m guessing — based on informal discussions with other physicians — that some of these responses reflect concerns about litigation for failure to diagnose cancer.

Many readers shared their perspectives by posting “reader remarks” in response to our recent summary of the USPSTF recommendation (JW Gen Med Jun 7 2012). One reader will continue to screen because she “has probably saved the life” of several men with screening. She might be right: Even skeptics must concede that individual lives occasionally are saved by screening. After all, if enough men undergo prostatectomy, somewhere in the mix are men who eventually would have died of prostate cancer. But, the important question is this: How many people must undergo screening, biopsies, prostatectomies, and radiation therapy to benefit one person? The Task Force concluded that the number needed to screen (NNS) and number needed to treat (NNT) are too high and result in adverse outcomes for too many people, whereas advocates of screening believe otherwise. Nothing is wrong with arguing that a particular NNS or NNT is too high, as long as we remember that selection of “appropriate” cutoffs are value judgments and not scientific truths.

Another reader entitled his remark “Can’t tell who is saved.” He correctly implies that when a man survives (cancer-free) after treatment for PSA-detected cancer, we can’t determine whether his particular life was saved by screening. From the European randomized screening trial (JW Gen Med Mar 14 2012), we can infer that roughly 1 of every 30 patients who received treatment for screening-detected cancer had his life extended, but we don’t know which particular man was “saved” and which 29 underwent treatment unnecessarily.

Several respondents claimed that mismanagement of PSA results and overtreatment of patients with low-risk prostate cancer — and not PSA screening — are the real problems. In my view, both the PSA test and overtreatment are problematic. No screening test has perfect sensitivity and specificity, but PSA test accuracy is especially poor: Fully 25% of men with PSA levels between 2 and 4 ng/mL have prostate cancer (JW Gen Med Jun 8 2004), and many men with PSA levels between 4 and 10 ng/mL don’t have prostate cancer. Sensitivity and specificity can be refined somewhat by using age-specific cutoffs, change in PSA level over time, or other variations; but so far, these other approaches have not been tested rigorously in controlled studies. Management approaches are all over the map because clinicians don’t quite know what to do when PSA levels go up a little: Biopsy now? Repeat in 1 year? Repeat in 6 months? Give antibiotics for “prostatitis,” and repeat in 1 month? And, regarding overtreatment of men with low-risk cancer, thoughtful urologists have told me, “I agree that we overtreat. But if a patient who doesn’t really need surgery says, ‘I want my cancer treated,’ what are we supposed to do? If we don’t do the surgery, he’ll go elsewhere.”

Another reader suggested that PSA screening is most beneficial in men older than 75. However, in the European screening trial, among men 70 or older at the time of randomization, researchers noted a trend toward higher mortality in screened versus nonscreened men. And, in the largest treatment trial (prostatectomy vs. watchful waiting in men with localized cancer; JW Gen Med Sep 16 2008), prostatectomy was associated with lower mortality only in men younger than 65.

One final interesting comment: A physician reader notes that when patients ask him whether he gets PSA tests himself, he replies that he does not, even though “my father and father-in-law had prostate cancer.” In some clinical encounters, it might be appropriate to share one’s personal medical decisions. But, I believe that when patients ask about PSA testing, physicians should explain why they agree or disagree with screening and leave their own healthcare decisions out of the discussion.

Source: Journal Watch General Medicine.