On Doctoring MEDLINE searches, with reference librarian comments, March 2000

The question was

What is the efficacy of the prostate specific antigen test as a diagnostic tool for prostate cancer and how can false positive results be avoided?

1     prostate specific antigen.mp. [mp=title, abstract, registry    results= 5116   
number word, mesh subject heading]
2     diagnosis.mp. [mp=title, abstract, registry number word,    results=182582   
mesh subject heading]
3     1 and 2    results= 745   
4     prostate cancer.mp. [mp=title, abstract, registry number    results= 8913   
word, mesh subject heading]
5     3 and 4    results= 512   
6    (sensitivity and specificity).mp. [mp=title, abstract,    results= 24296   
registry number word, mesh subject heading]
7     5 and 6    results= 77   
8     false positive reactions.mp. [mp=title, abstract, registry    results= 5081   
number word, mesh subject heading]
9     7 and 8    results= 2   
10     limit 9 to (local holdings and human and english language)    results= 2   

Reference Librarian comments

You are manipulating sets nicely, and using the LIMIT check-boxes, etc. -- but oooh, I wish you'd use the subject-headings rather than the ".mp." option. Admittedly, this is a hideous, cryptic "gotcha" in the current Ovid interface. It's hard to know exactly what to do when you get to the "mapping" page.

Let me say this another way. When you put "prostate specific antigen" in the keyword box -- then the system "maps" to a display which lets you select that term as a Medical subject heading (MeSH), along with a check-box for explode and focus (both of which you should usually do...) -- and it teases you into checking the ".mp. -- search for the word as a keyword" option. Don't do that. (Usually...)

If you use the MeSH term, then you get to subheadings, and then you could pick "diagnosis" from those subheadings, and this is how Medline works better.

I did the search below "my way" -- and the ideas are the same; the techniques a little different; the results are -- maybe -- better. I got eight instead of your two. But: you decide.

Thanks for participating in the assignment.

Medline 1991 to January 2000

#
Search History
Results

1
exp *Prostate-specific antigen/
2234

2
exp *Prostatic neoplasms/di [Diagnosis]
1485

3
1 and 2
609

4
exp "sensitivity and specificity"/
72190

5
exp predictive value of tests/
23872

6
3 and (4 or 5)
297

7
exp false positive reactions/
4970

8
6 and 7
8

<1>
AN 99130951
AU Zappa M. Ciatto S. Bonardi R. Mazzotta A.
IN Centro per lo Studio e la Prevenzione Oncologica, Florence, Italy.
TI Overdiagnosis of prostate carcinoma by screening: an estimate based on the
results of the Florence Screening Pilot Study [see comments].
CM Comment in: Ann Oncol 1998 Dec;9(12):1263-4
SO Annals of Oncology. 9(12):1297-300, 1998 Dec.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB OBJECTIVES: To estimate overdiagnosis (detection of latent carcinomas) as a
consequence of screening for prostate cancer. DESIGN: Based on actual screen
(first or repeat) detected and interval prostate cancer
rates observed in the Florence screening pilot study, a scenario was
simulated where males aged 60 years (or 65) had six biennal screens
and were followed up for four years. Overdiagnosis was
determined as the proportional excess of cancers detected by screening with
respect to that expected in its absence. SETTING: City of Florence, Italy,
from 1992 through 1995. POPULATION: 2,740 resident males, aged 60 to 74
years. RESULTS: Overdiagnosis was estimated to be 51% (95% confidence limits:
44%-55%) or 93% (85%-101%) for age 60 or 65 at entry. Comparison with other
screening experiences obtaining higher detection rates suggests that a more
aggressive screening approach could be associated with overdiagnosis
estimates as big as 200%-250%. CONCLUSIONS: Screening for prostate cancer is
associated with a relevant risk of overdioagnosis. As latent carcinomas can
not be presently identified, this would lead to overtreatment in most
overdiagnosed cases. The negative consequences of overdiagnosis (knowledge of
having a cancer) and of overtreatment (impotence,
incontinence, perioperatory death) may be extremely serious. In absence of
any scientific evidence of screening benefits (if any) screening should not
be recommended as a current practice, but should be limited to prospective
controlled studies designed to assess its cost-effectiveness.

<2>
AN 98181836
AU Masters JG. Keegan PE. Hildreth AJ. Greene DR.
IN Department of Urology, City Hospitals NHS Trust,
Sunderland, UK.
TI Free/total serum prostate-specific antigen
ratio: how helpful is it in detecting prostate cancer?.
SO British Journal of Urology. 81(3):419-23, 1998 Mar.
LM Dana Biomedical Library (Dana).
AB OBJECTIVE: To determine whether the use of free/total (f/t) serum prostate
specific antigen (PSA) ratio would help reduce the number of
prostate biopsies performed without compromising the detection of prostate
cancer. in the setting of a transrectal ultrasonography (TRUS) clinic.
PATIENTS AND METHODS: The study included 93 consecutive
patients referred to the clinic for TRUS and biopsy. Serum
samples were assessed for total PSA and free PSA,
and the f/t PSA ratio calculated: 70 biopsies were taken.
Patients over the age of 70 years with TRUS findings consistent with benign
prostatic hyperplasia and with PSA levels <
10 ng/mL were not biopsied. RESULTS: Tumour was detected in 23 patients;
receiver operating characteristic curves showed no advantage for the f/t PSA
ratio when compared with total PSA in detecting prostate cancer. If a f/t PSA
ratio of < 0.15 had been used to determine the necessity for biopsy in the
group with a total PSA of 4-10 ng/mL, then two-thirds of all tumours would
have been undetected. CONCLUSION: The f/t PSA ratio had no advantage over
total PSA in improving specificity at a given
sensitivity for detecting prostate cancer. Therefore, it
cannot be recommended as a means of decreasing unnecessary biopsies in
patients with a raised PSA level and/or an abnormal digital
rectal examination. This applied particularly to the group of patients with a
total PSA of 4-10 ng/mL.

<3>
AN 97041642
AU Kurita Y. Ushiyama T. Suzuki K. Fujita K. Kawabe K.
IN Department of Urology, Hamamatsu University School of Medicine, Japan.
TI PSA value adjusted for the transition zone volume in the
diagnosis of prostate cancer.
SO International Journal of Urology. 3(5):367-72, 1996 Sep.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB BACKGROUND: The aim of the present study was to improve the accuracy of the
prostate-specific antigen (PSA) density for
detecting prostate cancer by using the transition zone (TZ) volume instead of
the total prostate volume. METHODS: From April 1994 to October 1995, we
examined 164 consecutive patients (52-88 years old), with an elevated PSA
and/or abnormal digital rectal examination. All patients
underwent a transrectal ultrasound-guided biopsy. The PSA density for total
prostate volume (PSAD) and for TZ volume (PSAT) were
calculated from the transrectal ultrasound measurements. RESULTS: Forty-four
of the 162 patients (27.2%) had histological confirmation of prostate cancer
on biopsy. The area under the receiver-operator characteristic curve was
0.667 for PSA, 0.663 for PSAD, and 0.826 for PSAT. These
areas were not significantly different for PSA and PSAD.
However, PSAT was significantly superior to PSAD in differentiating benign
hyperplasia from prostate cancer (P < 0.01). CONCLUSION: The TZ
volume-adjusted PSA density (PSAT) is useful for selecting patients for
prostate biopsy from those with suspected prostate cancer.

<4>
AN 96221922
AU Miller LS. Armenakas NA. Motta J. Fracchia JA.
IN Division of Urology, Lenox Hill Hospital, New York, New York 10021, USA.
TI PSA divergence. A new parameter for the accurate longitudinal assessment of
prostatic disease.
SO American Journal of Clinical Oncology. 19(3):217-22, 1996 Jun.
LM Dana. Incomplete holdings, check catalog.
AB Prostate-specific antigen (PSA)
and the various parameters derived utilizing this marker
have increased our ability to diagnose early prostatic
disease; however, their accuracy in identifying the etiology of the disease
remains somewhat limited. We propose a new PSA derivative, termed "PSA
divergence" (PSADI), defined as the change in serum PSA over time (years)
divided by the change in prostatic volume over time (years),
to more accurately distinguish benign, premalignant, and
malignant prostatic diseases. In this study, we evaluated
160 subjects with a PSA >4.0 ng/ml who were found by transrectal
ultrasound-guided biopsy (TRUS) to have either benign
prostatic hyperplasia or prostatic
intraepithelial neoplasia. These men were followed at 6 or 12 months with
serial PSA, digital rectal exam (DRE), and TRUS with
rebiopsy. Data analysis demonstrated a statistically significant (p < 0.05)
correlation between PSADI and each final pathologic outcome,
suggesting that PSADI is useful in distinguishing among intraepithelial
neoplasia and benign and malignant
prostatic disease.

<5>
AN 96079834
AU Parkes C. Wald NJ. Murphy P. George L. Watt HC. Kirby R. Knekt P.
Helzlsouer KJ. Tuomilehto J.
IN Department of Environmental and Preventive Medicine,
Wolfson Institute of Preventive Medicine, Medical College of St Bartholomew's
Hospital, London.
TI Prospective observational study to assess value of prostate
specific antigen as screening test for prostate cancer [see
comments].
CM Comment in: BMJ 1996 Mar 16;312(7032):708-9; discussion 709-10, Comment in:
BMJ 1996 Mar 16;312(7032):709; discussion 709-10, Comment in: BMJ 1996 Mar
16;312(7032):709-10
SO BMJ. 311(7016):1340-3, 1995 Nov 18.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB OBJECTIVE--To evaluate measurement of serum prostate specific
antigen as a potential screening test for future clinical
prostate cancer among healthy men. DESIGN--Nested case-control study with
stored serum samples collected from 49,261 men with follow up using national
death and cancer registration systems. SUBJECTS--265
asymptomatic men who subsequently developed clinical prostate cancer
and 1055 controls matched for age, study centre,
and duration of storage of samples. MAIN OUTCOME
MEASURES--Distribution of concentrations of the antigen in
men who developed prostate cancer and in controls.
RESULTS--Prostate specific antigen concentrations were
significantly higher in men who subsequently developed prostate cancer than
in controls. In the first three years after blood collection the median
concentration was 23 times greater in cases than in controls of the same age
at the same centre (that is, 23 multiples of the median). A smaller
difference persisted thereafter; 4.0 multiples of the median 3-6 years after
blood collection, 3.6 6-10 years, and 1.8 after 10 years. In
the first three years the proportion of men who developed prostate cancer
and had raised levels of the antigen (> or
= 12 multiples of the median) (detection rate or
sensitivity) was 81% (95% confidence interval 54% to 96%).
The proportion of men who did not develop prostate cancer but had levels this
high (false positive rate) was only 0.5%.
CONCLUSION--Prostate specific antigen measurement is a
highly discriminatory screening test for prostate cancer among healthy men.
In the general population, 60-74 year old men who had > or = 12 times the
normal median level would have about a 50% chance of developing clinical
prostate cancer in the next three years. Measurement of this
antigen is a good enough screening test to justify a
randomised controlled trial to determine any reduction in
mortality from prostate cancer.

<6>
AN 97006197
AU Smith DS.
IN Division of Urologic Surgery, Washington University School of Medicine, St.
Louis, Missouri, USA.
TI Early detection of prostate cancer with PSA: the Washington University
experience.
SO Canadian Journal of Oncology. 4 Suppl 1:57-62, 1994 Nov.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.

<7>
AN 94112795
AU Bazinet M. Meshref AW. Trudel C. Aronson S. Peloquin F. Nachabe M.
Begin LR. Elhilali MM.
IN Department of Urology, McGill University, Montreal, Quebec, Canada.
TI Prospective evaluation of prostate-specific
antigen density and systematic biopsies for
early detection of prostatic carcinoma [see comments].
CM Comment in: Urology 1994 Jul;44(1):150-1
SO Urology. 43(1):44-51; discussion 51-2, 1994 Jan.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB Significant controversies persist in regard to the need for systematic
biopsies in patients with serum prostate-specific
antigen (PSA) levels above 4 ng/mL (Hybritech assay),
especially if they show no signs of prostatic cancer on
digital rectal examination (DRE) or transrectal ultrasonography (TRUS). We
evaluated 565 consecutive patients referred to us for prostatism, suspicious
lesions on DRE, or an elevated serum PSA level. These patients do not
represent a purely screened population. A detection rate of 38.4 percent was
achieved by performing directed biopsies of suspicious lesions on DRE
and/or TRUS, and systematic biopsies of all
patients with serum PSA levels above 4 ng/mL. Among 142 patients with serum
PSA between 4.1 and 10 ng/mL, but without suspicion for
cancer on DRE and TRUS (DRE- TRUS-), a large number of
patients (6.2) were subjected to systematic biopsies to detect one cancer. A
receiver-operating characteristics curve for PSA density (PSAD) applied to
this population confirmed that the best cut-off point for biopsies was a PSAD
of 0.15, below which only two of twenty-three cancers would have been missed,
sparing biopsies in 77 of 142 patients. A similar approach was applied to
DRE- TRUS- patients with serum PSA levels above 10 ng/mL. The number of
cancers in those with serum PSA between 10.1 and 14 ng/mL
was too low to establish a PSAD cut-off point. In patients with serum PSA
above 14 ng/mL, the best PSAD cut-off point for biopsies was 0.3, below which
two of thirteen cancers would have been missed, sparing biopsies in 19 of 39
patients. We conclude that PSAD can safely reduce the number of patients
subjected to systematic biopsies without significantly compromising cancer
detection.

<8>
AN 93377306
AU Wolf JS Jr. Shinohara K. Carroll PR. Narayan P.
IN Department of Urology, University of California School of Medicine, San
Francisco.
TI Combined role of transrectal ultrasonography, Gleason score,
and prostate-specific
antigen in predicting organ-confined prostate cancer.
SO Urology. 42(2):131-7, 1993 Aug.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB Prostate cancer staging is frequently inaccurate. By combining transrectal
ultrasonography (TRUS) with a retrospectively derived grade-stratified
prostate-specific antigen (PSA-GS) scale,
we demonstrated 77 percent staging accuracy in 155 men with clinically
localized prostate cancer undergoing radical prostatectomy. When used as the
first step in a staging algorithm, PSA-GS (Score > or = 7: PSA > or = 4.0
ng/mL, uncontained; Score = 5 or 6: PSA > or = 8.0 ng/mL, uncontained; Score
< or = 4: PSA > or = 16.0 ng/mL, uncontained) had a
sensitivity of 75 percent and a
specificity of 72 percent. The addition of TRUS to the
staging algorithm, necessary only in patients with negative predictions by
PSA-GS (46%), increased the sensitivity to 86 percent
and the negative predictive
value to 79 percent, while positive
predictive value was unchanged at 77
percent. The combination of TRUS with PSA < 4 ng/mL or > or = 16 ng/mL
identified subsets of patients with 85 percent and 88
percent likelihood of contained and uncontained disease,
respectively. Our algorithm minimizes operator dependency by requiring TRUS
in less than half of the patients. It produced improved staging, but the
overall results were inaccurate in 23 percent of patients. Further
refinements in prostate cancer staging are still necessary.