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Prostate-specific antigen (PSA) measurements after primary treatment reflect residual tumor burden among men with prostate cancer. Using a mixture model analysis, we identified distinct trajectories of post-treatment PSA measurements and evaluated their associations with prostate cancer mortality. The study sample included 623 US Veterans treated for prostate cancer with curative intent during 1991-1995; 225 men received surgery and 398 men received radiation therapy. Post-treatment PSA measurements over a 2-year period for each patient were evaluated in latent class mixture models using the SAS TRAJ procedure, and groups of men with distinct trajectories of PSA were identified. These groups were then assessed for associations with 10-year prostate cancer mortality using proportional hazards analysis. Analyses identified three distinct groups-representing patterns of both initial values and changes in PSA over time-after surgery (n=172/31/14) and radiation therapy (n=253/103/22). Men in groups with patterns of higher (compared with the group with lowest) PSA values tended to have worse survival experience: HRs for prostate cancer mortality were 3.45 (P=0.18) and 22.7 (P<0.001) for surgery, and 2.70 (P=0.005) and 18.1 (P<0.001) for radiation therapy. The results indicate that PSA measurements after surgery or radiation therapy with curative intent include groups of men with a diverse spectrum of prognosis for prostate cancer mortality. Although contemporary PSA levels are lower than those observed in the study sample, the corresponding trajectory patterns may become evident shortly after the time of diagnosis and treatment., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Changes in prostate-specific antigen (PSA) values are often reported as velocity or doubling time. We compared the association of these two calculations-at the time of PSA failure after primary treatment for prostate cancer-with prostate cancer mortality. From a source population of 1313 US Veterans with prostate cancer, including 623 treated with curative intent, the study population included 242 men experiencing biochemical failure, 81 after surgery and 161 after radiation therapy. Clinically relevant calculations of PSA velocity (linear slope) and PSA doubling time (logarithmic slope) were assessed for their association with 11-16 years of mortality from prostate cancer. Death due to prostate cancer occurred in 52/242 (21.5%) men. Among men receiving surgery, PSA velocity ≥1.0 ng/mL/year was associated with increased prostate cancer mortality (HR=4.2, p value=0.037), whereas doubling time ≤12 months did not confer risk (HR=1.0, p value=0.95). Conversely, among patients receiving radiation therapy, doubling time ≤12 months was associated with increased prostate cancer mortality (HR=2.4, p value=0.049), but velocity did not confer a statistically significant risk (HR=3.8, p value=0.19). When assessing risk of prostate cancer mortality, PSA velocity can be more predictive after surgery and PSA doubling time can be more predictive after radiation therapy., (Copyright © 2016 American Federation for Medical Research.)

Objective: Prostate cancer is common and prostate cancer screening is controversial; this retrospective observational study was conducted to determine the prevalence of digital rectal examination (DRE) in those in whom a prostate-specific antigen (PSA) test was performed., Methods: A manual review was performed of the electronic medical record for male veterans in the VA Connecticut Healthcare System without a history of known prostate cancer aged between 50 and 74 years who underwent PSA testing., Main Outcomes: Documentation of DRE (or refusal) within 12 months before or after the performance of a PSA test., Results: Less than half (47.6%) of patients underwent DRE. An additional 6.9% were offered DRE and refused. Although the provider gender was not associated with DRE, resident physicians were less likely to perform DRE than nonresidents; P = 0.01. Patients whose PSA was > 4.0 ng/mL were more likely to undergo DRE than those whose PSA was ≤ 4.0 ng/mL; P = 0.002. Those with body mass index (BMI) > 40 kg/m 2 were less likely to undergo DRE than those with BMI < 30 kg/m 2 ; P = 0.04., Conclusions: Screening for prostate cancer remains controversial. We found a low rate of DRE among veterans in whom prostate cancer screening was entertained. Although the provider gender does not seem to influence DRE, resident physicians were less likely to perform DRE than other providers. Our finding that BMI > 40 kg/m 2 is associated with a lower rate of DRE than those with BMI < 30 kg/m 2 is consistent with screening for other cancers and should be explored further.

Background: Among men treated for prostate cancer, increasing prostate-specific antigen (PSA) is known as biochemical failure or biochemical recurrence (BCR). The impact of BCR on subsequent mortality is uncertain, however, especially given competing causes of death., Methods: To describe patterns of BCR and subsequent mortality, we conducted an observational study in a community-based, "high-comorbidity" setting of 623 US veterans diagnosed as having prostate cancer from 1991 to 1995 and receiving radical prostatectomy or radiation therapy. The main outcome measures were BCR, defined as a PSA level of 0.4 ng/mL or higher (treated with surgery) or "PSA nadir+2 ng/mL" (treated with radiation therapy), and prostate cancer mortality, determined through 2006., Results: With 5-, 10-, and 15-year follow-up periods, respectively (for all results shown herein), the cumulative incidence of BCR after prostatectomy (n=225) was 34%, 37%, and 37%; prostate cancer mortality among men who failed treatment (n=81) was 3%, 11%, and 21%. Among men receiving radiation therapy (n=398), the cumulative incidence of BCR was 35%, 46%, and 48%; prostate cancer mortality among those who failed treatment (n=161) was 11%, 20%, and 42%. Overall, BCR was associated with an increased risk of death from prostate cancer in the study population, but the individual probability of this outcome was relatively low., Conclusions: Biochemical recurrence is associated with increased prostate cancer mortality, yet when BCR occurs only a minority of men subsequently die of their disease. The phrase "most men die with prostate cancer, not of it" applies to elderly veterans, even after failure of primary treatment. New strategies for defining and managing treatment failure in prostate cancer are needed.

Objective: To evaluate prognosis in prostate cancer by assessing the independent effect of selected molecular factors (e.g. markers of cell-cycle regulation), in addition to the effect of traditional clinical factors (e.g. anatomical stage, histological grade), in predicting long-term mortality among men newly diagnosed with prostate cancer., Patients and Methods: In a community-based population of 64 545 USA veterans aged >/= 50 years and receiving ambulatory care during 1989-90 at nine Veterans Affairs (VA) medical centres in New England, 1274 had incident prostate cancer during 1991-95. We obtained the medical records and diagnostic tissue for these men, and then extracted demographic data and clinical information, and conducted immunohistochemical assays of molecular markers in biopsy tissue, as potential prognostic factors. In this interim analysis, data on 250 patients were analysed; the main outcome was overall mortality to 31 December 2003, providing 8-13 years of follow-up., Results: In 228 (91%) patients with available medical record and laboratory data, the median age was 72 years and the median prostate-specific antigen level was 10.4 ng/mL. In adjusted (multivariate) analyses that included traditional prognostic factors, bcl-2 staining (hazard ratio 2.14, 95% confidence interval 1.27-3.58, P = 0.004) and high microvessel density (1.76, 1.19-2.60; P = 0.005) had an independent effect on the outcome., Conclusions: Bcl-2 and microvessel density are independent predictors of subsequent death among men with prostate cancer and might have a clinical role in assisting in deciding on treatment.

Background: Prostate-specific antigen "velocity" (slope) is promoted as a diagnostic test for prostate cancer, but its clinical usefulness is uncertain. Accordingly, we evaluated the sensitivity of prostate-specific antigen (PSA) velocity among men who are diagnosed subsequently with prostate cancer., Methods: Among 64,545 men receiving primary care at any of nine Veterans Affairs Medical Centers during 1989-1990, 1,313 men at least 50 years old had an incident diagnosis of prostate cancer during 1991-1995. PSA velocity values obtained prior to diagnosis ("test") were compared with results from prostate biopsies ("truth")., Results: Among men (n = 493) with at least two tests before diagnosis, the sensitivity of PSA velocity > or = 0.75 ng/mL/yr was 75.5% (95% confidence interval [CI] 71.7-79.3) overall and 48.1% (95% CI 34.8-61.5) among men with normal values of PSA (< 4.0 ng/mL). Based on published data for specificity and prevalence, the estimated positive predictive value of PSA velocity > or = 0.75 ng/mL/yr is as low as 5%., Conclusion: PSA velocity may have limited usefulness as a diagnostic test for prostate cancer.

Background: Screening for prostate cancer is done commonly in clinical practice, using prostate-specific antigen (PSA) tests or digital rectal examination (DRE). Evidence is lacking, however, to confirm a survival benefit among screened patients. We evaluated the effectiveness of PSA, with or without DRE, in reducing mortality., Methods: We conducted a multicenter nested case-control study at 10 Veterans Affairs medical centers in New England. Among 71 661 patients receiving ambulatory care between 1989 and 1990, 501 case patients were identified as men who were diagnosed as having adenocarcinoma of the prostate from 1991 through 1995 and who died sometime between 1991 and 1999. Control patients were men who were alive at the time the corresponding case patient had died, matched (1:1 ratio) for age and Veterans Affairs facility. The exposure variable (determined blind to case-control status) was whether PSA testing or DRE was performed for screening prior to the diagnosis of prostate cancer among case patients, with the same time interval for control patients. The association of screening and overall or cause-specific (prostate cancer) mortality was adjusted for race and comorbidity., Results: A benefit of screening was not found in our primary analysis assessing PSA screening and all-cause mortality (adjusted odds ratio, 1.08; 95% confidence interval, 0.71-1.64; P=.72), nor in a secondary analysis of PSA and/or DRE screening and cause-specific mortality (adjusted odds ratio, 1.13; 95% confidence interval, 0.63-2.06; P=.68)., Conclusions: These results do not suggest that screening with PSA or DRE is effective in reducing mortality. Recommendations for obtaining "verbal informed consent" from men regarding such screening should continue.

Background: The goals of the current study were to describe patterns of prostate specific antigen (PSA) surveillance for prostate carcinoma progression in a community-based cohort of patients and to identify independent clinical and sociodemographic factors that predict the frequency of surveillance., Methods: Patients diagnosed with localized prostate carcinoma from October 1, 1991 to December 31, 1992 in New Haven and Hartford, Connecticut, were identified. Data were collected through standardized outpatient medical record review. Multivariate statistical methods were used to determine the factors that independently predicted the frequency of surveillance., Results: Six hundred fifty-eight men with localized prostate carcinoma were included in the cohort. Forty-five percent of all patients were tested at least once annually, and 69% were tested at least once every 2 years. Multivariate models indicated that African American men were half as likely as Caucasian men to receive annual testing (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.24-0.97). Men diagnosed at age 70 years or older were 38% less likely to have annual testing than men diagnosed between the ages of 65 and 69 (OR, 0.62; 95% CI, 0.41-0.94). A higher Gleason score and PSA at presentation also were associated independently with higher rates of annual PSA surveillance., Conclusions: Postdiagnosis PSA surveillance is common, although not universal. African American men were at significantly greater risk for receiving less frequent testing compared with Caucasian men. This disparity in access to care may explain, in part, previously observed racial differences in survival in prostate carcinoma. Further research is needed to identify the reasons for the racial disparity in PSA surveillance and to design interventions to lessen these differences., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11492)

The role of prostate specific antigen (PSA) as a screening test for prostate cancer is controversial. Proponents of screening emphasize that early detection can lead to discovery of organ-confined disease and the potential for cure. Opponents point to the lack of credible evidence that screening is associated with a decrease in mortality. In addition, population-based screening (with subsequent diagnosis and treatment in many men) can be associated with considerable morbidity and mortality in the context of a disease that is often not fatal. This report examines the limitations of PSA as a screening test and supports an approach using "verbal informed consent" to identify patients who should be tested.

Context: Screening for prostate cancer with serum prostate-specific antigen (PSA) is controversial. Ideally, patients should be aware of the potential benefits and risks related to testing., Purpose: To assess whether patients remembered having PSA screening and to determine whether they recalled having a discussion with their primary care provider about the pros and cons of such testing., Methods: A questionnaire was sent to patients who had PSA screening ordered by a primary care practitioner during a 2-month period at a university-affiliated Veterans Affairs medical center. Approximately 3 months after the PSA test was done, patients were asked about their baseline health as well as their knowledge of and attitudes toward screening with PSA and treatment for prostate cancer., Results: The overall response rate was 197 out of 421 (46%) patients. Among 173 eligible respondents without prostate cancer, 53 (31%) were unaware that their physician had ordered a PSA test. Among the 120 patients who were aware of receiving the test, only 56 (47%) recalled having a discussion with their primary care provider about the risks and benefits of screening. Support for the test was more common among patients who recalled having PSA screening than those who did not recall having the test (91% vs. 70%, respectively; P = 0.003)., Conclusions: Patients who have PSA screening often are unable to recall relevant facts about the test and may have no knowledge of its associated risks and benefits. The role and effectiveness of obtaining verbal informed consent for PSA screening should be re-evaluated.

Although screening for prostate cancer with prostate-specific antigen (PSA) or digital rectal exam (DRE) is commonly done, evidence is currently lacking to show a benefit of such testing on survival. The current study used a nested case-control design to assess the impact of screening with PSA (with or without DRE) on mortality.Among 71,661 patients receiving ambulatory care during 1989–1990 at any of ten VA Medical Centers in New England, case subjects were men diagnosed with prostate cancer from 1991–1995 who died during 4–9 years of follow-up. Control subjects (1:1 sampling ratio) were men who are alive at the time of death of the corresponding case, matched for year of birth and VA facility. The exposure variables were screening with PSA alone, or PSA and DRE, done for screening purposes; potential screening tests must have occurred prior to the diagnosis of prostate cancer for the cases or the corresponding date for controls. The assessment of screening was also done blind to case-control status, and tests were classified by an algorithm that took into account the clinical context of the exams.A total of 501 matched case and control subjects (1002 total patients) were included in final analyses. The frequency of screening with PSA was similar among cases (14.0%) and controls (13.0%); with an unadjusted odds ratio of 1.10 (95% C.I. 0.75 to 1.62). After adjusting for race and comorbidity, the odds ratio remained quantitatively and statistically non-significant at 1.08 (95% C.I. 0.71 to 1.64). Screening was also not associated with improved survival in analyses involving screening with PSA or DRE, among men less than 70 years of age, and using data from patients during last three years of intake when PSA testing was more commonly done.The results do not support the effectiveness of PSA or DRE in screening for prostate cancer. [Copyright &y& Elsevier]

Increases in prostate-specific antigen (PSA) are often used as a surrogate endpoint (e.g., for mortality) when evaluating potential benefits of therapy for cancer of the prostate (CaP). In this context, different definitions of “failure” have evolved for each type of treatment (e.g., surgery, radiation), leading to potential confusion when physicians and patients evaluate data on outcomes. Our purpose was to compare existing, and evaluate a new, definition(s) of PSA failure.Patients were from an ongoing study of 1320 men diagnosed with CaP in the New England Veterans Affairs Healthcare System during 1991–1995. To ensure an adequate spectrum of CaP, a random sample of 125 men with CaP who died were first identified, and 125 age-matched men with CaP who were still alive were selected from the same VA sites. Data regarding baseline characteristic and post-treatment PSA (4–9 year follow-up) were collected. Proportions of men with PSA failure and median time to PSA failure were determined, regardless of actual therapy received, based on criteria a) after prostatectomy (any detectable PSA); b) after radiotherapy, as per the American Society of Therapeutic Radiation and Oncology (ASTRO) (three consecutive rises after a nadir PSA); and c) applying a threshold for PSA slope (1 ng/mL/year).Among 250 men, 12 (4.8%) were excluded (e.g., unavailable records). For the remaining 238 patients, surgical failure was evident in 165 (69.3%), whereas ASTRO classified 86 (36.1%) as having failed; kappa statistic for concordance = 0.28 (95% confidence interval 0.17–0.38), indicating “poor” agreement. The median time to PSA failure also varied widely: 4.5 months for surgery vs. 37.6 months per ASTRO. Failure based on PSA slope identified 112 men (47.1%); the median time to failure (22.7 months) was also intermediate between the existing approaches.Currently used definitions of treatment failure in CaP can produce substantially different results when assessing the same clinical phenomena. A new definition of PSA failure, based on slope of PSA, is easy to use and applicable regardless of type of treatment. This research can improve the ability of providers (and their patients) to make informed and appropriate decisions regarding treatment for prostate cancer. [Copyright &y& Elsevier]