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CME

PSA Value Is a Poor Predictor of Prostate Cancer Outcome

  • Authors: News Author: Allison Gandey
    CME Author:
    Désirée Lie, MD, MSEd
  • CME Released: 4/16/2007; Reviewed and Renewed: 4/18/2008
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 4/18/2009
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Target Audience and Goal Statement

This article is intended for primary care clinicians, urologists, oncologists, and other specialists who care for men with prostate cancer.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Describe baseline PSA value and rate of rise of PSA level as predictors of lethal outcome for early prostate cancer.
  • Characterize the ability of baseline PSA value and rate of rise of PSA level to distinguish between need for watchful waiting or aggressive therapy for early localized prostate cancer.


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Author(s)

  • Allison Gandey

    Allison Gandey is a journalist for Medscape. She is the former science affairs analyst for the Canadian Medical Association Journal. Allison, who has a master of journalism specializing in science from Carleton University, has edited a variety of medical association publications and has worked in radio and television. She can be contacted at [email protected]

    Disclosures

    Disclosure: Allison Gandey has disclosed no relevant financial relationships.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California

    Disclosures

    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.


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CME

PSA Value Is a Poor Predictor of Prostate Cancer Outcome

Authors: News Author: Allison Gandey CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME Released: 4/16/2007; Reviewed and Renewed: 4/18/2008

Valid for credit through: 4/18/2009

processing....

April 16, 2007 — A study shows that while prostate-specific antigen (PSA) measurement remains an important monitoring tool, it performs poorly in distinguishing those who will develop lethal prostate cancer from those at low or no risk of disease progression. The results are reported in the April 4 issue of the Journal of the National Cancer Institute, where the authors call for better decision-making tools for active monitoring of patients with early disease.

"In this study, both baseline PSA and rate of change in PSA during the first 2 years of follow-up carried prognostic information," write Katja Fall, MD, PhD, from the Karolinska Institutet in Stockholm, Sweden, and colleagues. "However, despite extensive exploration of different statistical models, we could not substantiate any PSA curve characteristic as a good classifier of who would develop lethal disease and who would not."

In an accompanying editorial, Dipen J. Parekh, MD, from the University of Texas Health Science Center in San Antonio, and colleagues point out that the patients in the current study were substantially different from most patients with localized prostate cancer today in countries where PSA screening is highly prevalent, such as the United States. "PSA levels were above 10 ng/mL in 48% of the patients in that population and more than 60% of men had tumors that were palpable on rectal examination," they write. "At diagnosis, these were high-volume tumors, tumors more likely to exhibit stronger PSA kinetics driving more favorable PSA operating characteristics than would be expected from populations containing higher fractions of screen-detected cancers. As a result, we would expect less optimistic performance of these PSA measures in a typical US population."

In ideal circumstances, the editorialists write, a man undergoing active surveillance for prostate cancer expects that his PSA data will tell his clinician 1 of 2 things: (1) he has a potentially deadly tumor that must be treated now or (2) he has an indolent tumor that can be safely watched, sparing him the adverse effects of treatment. "If we simply use a PSA doubling time of 5 years as a guide, in this group of patients approximately 36% of deadly tumors would be missed and 40% of men with indolent tumors would be treated unnecessarily," they explain. "If our goal is to find all lethal cancers, the very best trigger for treatment would be a PSA value of 7 ng/mL. The trade-off for this threshold is that approximately 80% of men with nonlethal tumors would then be treated."

In the current study, Fall and colleagues concur that many patients with prostate cancer undergo aggressive local treatment without any survival benefit. The implications from these data are troublesome, the editorialists comment. "Without becoming despondent and simply treating all men with prostate cancer — accepting the substantial risk of overtreatment and its consequences — how can we better identify the patient with low-risk disease in whom active surveillance is a reasonable option for management?"

Not Sensitive or Specific Enough to Identify Lethal Tumors

In their editorial, Parekh and colleagues propose that the first step is to acknowledge that, although PSA level and its kinetics are clearly associated with the behavior of individual prostate cancers, they are not sensitive or specific for the tumor that will ultimately cause harm to a patient. "We have found the same results with PSA as a measure of the risk of prostate cancer," they point out. "Specifically, in our analysis of the Prostate Cancer Prevention Trial, we found that other measures such as rectal examination findings, family history, ethnicity, age, and prior prostate biopsy results all provided independent predictive value of prostate cancer risk."

In the current study, part of the Scandinavian Prostate Cancer Group research, Dr. Fall and colleagues analyzed the rate of change of PSA levels in 267 men from Sweden, Finland, and Iceland who were diagnosed with early localized prostate cancer. The researchers recorded the PSA levels for the first 2 years after diagnosis to capture the patients' early PSA patterns. The men in the study received no curative treatment for the first 2 years but were closely watched for signs of progression.

At the end of follow-up, 34 (13%) patients died from prostate cancer and 18 (7%) developed metastatic prostate cancer. Although initial PSA values and the rate of change were associated with later development of lethal prostate cancer, they were not accurate enough to predict lethal cancer.

"Strengths of our study include its prospective design, large size, complete follow-up, and standardized classification of deaths with blinding for any antecedent treatment," Fall and colleagues write. "As a corollary, our findings should be generalizable also to other settings, such as screening," they note. "In addition, the results seemed independent of Gleason score — a fact that further underpins their generalizability."

The Swedish Cancer Society and the National Institutes of Health supported this study. Dr. Fall has disclosed being supported partly by a Postdoctoral Traineeship Award from the US Department of Defense.

J Natl Cancer Inst. 2007;99:526-532.

Clinical Context

According to the authors of the current study, watchful waiting (treatment postponed until signs of progression) has been the standard for men newly diagnosed with localized prostate cancer because of the excellent prognosis associated with untreated localized cancer. Tumor growth rate is thought to be reflected by the rate of increase in concentration of PSA, and the early PSA curve may reflect biologic behavior of the tumor and distinguish those tumors that warrant intensive early treatment vs those that are slowly growing and nonlethal, they write.

This is a prospective multicenter trial conducted at 14 centers in Finland, Sweden, and Iceland to determine the predictive values of baseline PSA level and early rate of rise of PSA level for lethal outcomes of early localized prostate cancer.

Study Highlights

  • Inclusion criteria were men younger than age 75 years with newly diagnosed, primary, untreated prostate adenocarcinoma, clinical stage T1b, T1c, or T2, with an initial PSA value of less than 50 ng/mL, nuclear grade 1 or 2 tumor, negative bone scan, and no obstruction of the upper urinary tract.
  • Excluded were those with metastases and without subsequent PSA values within 6 months and 2 years and men diagnosed with lethal prostate cancer within 2 years.
  • Transurethral resection was used for subsequent local progression and hormonal therapy for dissemination.
  • 267 men were observed for a mean of 8.5 years.
  • Cause of death was determined by an independent committee.
  • Distant metastases were considered present if bone scans or radiographs showed them or lymph nodes above the diaphragm showed evidence of disseminated disease.
  • A patient was classified as having lethal prostate cancer when the occurrence of metastasis was first documented.
  • PSA levels were examined for the first 2 years - the longest clinicians were believed to be willing to delay a reevaluation of treatment options.
  • PSA velocity (PSAV; ng/mL per year) and PSA doubling time (PSADT) were calculated from standardized assays of PSA.
  • At baseline, two thirds of participants were aged 60 to 69 years, two thirds had tumor stage T2, two thirds had a Gleason score of 2 to 6, and 30% had a PSA level of 10 to 20 ng/mL with 18% having levels greater than 20 ng/mL.
  • Mean baseline PSA value was 12 ng/mL.
  • Mode of detection of tumor: 40%, symptoms; 29%, coincidental.
  • 5% received transurethral resection within 2 years of baseline, and 49% received hormonal therapy after 2 years from baseline.
  • During follow-up 13% of men died from prostate cancer, all of whom had developed clinically detectable metastases.
  • 7% developed metastases and were still alive at the end of follow-up, and 12% died from other causes.
  • Both baseline PSA value and PSAV in the first 2 years were significantly associated with lethal prostate cancer in age-adjusted analysis.
  • Similar results were obtained after restricting analysis to men with Gleason scores less than 7.
  • Time-dependent receiver operating characteristic curves were calculated 6 and 10 years after randomization.
  • No single cutoff point for any measure of baseline PSA or relative PSAV yielded high sensitivity with high specificity.
  • A baseline PSA value of 10 ng/mL predicted lethal prostate cancer 6 years from baseline with a sensitivity of 0.69 and specificity of 0.58; a cutoff value of relative PSAV of 0.14 ng/mL per year corresponding to a PSADT of 5 years yielded a sensitivity of 0.69 and a specificity of 0.57.
  • Restricting analysis to Gleason scores of less than 7 did not change the accuracy of the tests.
  • No cutoff points allowed a division of the patient cohort into 2 groups with clearly different treatment needs.
  • The 6-year cumulative incidence was 7% among men with a PSADT of 5 years or more and 17% among men with a PSADT of less than 5 years, corresponding to a relative risk of 2.6.
  • Although rise of PSA level corresponded positively to lethal prostate cancer, 7% of men classified as "low risk" would still die from prostate cancer.
  • The authors concluded that PSA value at baseline and PSAV were poor predictors and could not identify treatment directed to address lethal prostate cancer outcome.

 

Pearls for Practice

  • Baseline PSA and PSAV may predict progression to metastatic lethal prostate cancer in men with localized prostate cancer.
  • Baseline PSA and rate of change in PSA level are poor predictors of lethal prostate cancer among patients with localized prostate cancer treated with watchful waiting.

 

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