Characterization of Prostate Cancer Missed by Sextant Biopsy

Bak, John B.; Landas, Steve K.; Haas, Gabriel P.

doi:10.3816/cgc.2003.n.019

Cited by 28 publications

(24 citation statements)

References 21 publications

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“…Prostate-specific antigen (PSA)-based screening has proved effective in reducing prostate cancer (PC)-specific mortality(1, 2), but is associated with overdiagnosis of low-malignant cancers, and underdiagnosis of potentially lethal cancers(3, 4). There is a need for a more effective screening strategy that improves upon the benefits in terms of increased sensitivity and reduces harm by avoiding unnecessary biopsies and overdiagnosis.…”

Section: Introductionmentioning

confidence: 99%

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

et al. 2016

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Background Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer (PC) compared to prostate-specific antigen (PSA) and systematic biopsies (SB). Objective To compare sequential screening (PSA + MRI) with conventional PSA screening. Design, Setting and Participants Of 384 attendees in the 10th screening round of the Göteborg randomised screening trial, 124 men, median age 69.5, had a PSA of ≥1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA ≥3.0 ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in men with tumour-suspicious findings on MRI. Three screening strategies were compared (PSA≥3.0+SB; PSA≥3.0+MRI+TB and PSA≥1.8+MRI+TB). Outcome Measurements and Statistical Analysis Cancer detection rates, sensitivity and specificity were calculated per screening strategy and compared using McNemar´s test. Results and Limitations In total, 28 PC were detected, of which 20 were diagnosed in biopsy-naïve men. Both PSA≥3.0+MRI and PSA≥1.8+MRI significantly increased specificity compared with PSA≥3.0+SB (0.92 and 0.79 vs. 0.52; p<0.002 for both), while sensitivity was significantly higher for PSA≥1.8+MRI compared with PSA>=3.0+MRI (0.73 vs. 0.46, p=0.008). The detection rate of significant cancer was higher with PSA≥1.8+MRI compared to PSA≥3.0+SB (5.9 vs. 4.0%), while the detection rate of insignificant cancer was lowered by PSA≥3.0+MRI (0.3 vs. 1.2%). The primary limitation of this study is the small sample of men. Conclusion A screening strategy with a lowered PSA cut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening. Patient Summary Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in prostate cancer screening, and we found promising potential of using magnetic resonance imaging in addition to prostate-specific antigen.

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Section: Introductionmentioning

confidence: 99%

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

et al. 2016

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“…Importantly only biopsy results were used to cull the cancer subgroup in this patient cohort. Needle biopsy by itself, in addition to being invasive, has a well documented false negative rate, missing 28% of existing prostate cancers (31). This adds to the complexity of the study cohort as a benign subset (as defined by negative biopsy) may very well harbor neoplasm that went undetected.…”

Section: Discussionmentioning

confidence: 99%

Humoral Response Profiling Reveals Pathways to Prostate Cancer Progression

Taylor

Pal

et al. 2008

Molecular & Cellular Proteomics

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There is considerable evidence for an association between prostate cancer development and inflammation, which results in autoantibody generation against tumor proteins. This immune system-driven amplification of the autoantibody response to intracellular antigens can serve as a sensitive tool to detect low abundance serum proteomic tumor markers for prostate cancer as well as provide insight into biological processes perturbed during cancer development. Here we examine serum humoral responses in a cohort of 34 patients with either benign prostatic hyperplasia or clinically localized prostate cancer (PCa). The experimental strategy couples multidimensional liquid-phase protein fractionation of localized and metastatic prostate cancer tissue lysates to protein microarrays and subsequent mass spectrometry. A supervised learning analysis of the humoral response arrays generated a parsimonious predictor having 78% sensitivity and 75% specificity in distinguishing PCa from benign prostatic hyperplasia in a cohort of American males with elevated prostate-specific antigen. Enrichment analysis of the PCa-specific humoral signature revealed large scale immune reprogramming mediated by STAT transcription factors and the generation of autoantibodies to enzymes involved in nitrogen metabolism. Meta-analysis of independent prostate cancer gene expression data validated the presence of STAT-induced immunomodulation. Concomitant validation of elevated levels of the nitrogen metabolism pathway was obtained by direct measurement of metabolic levels of glutamate and aspartate in prostate cancer tissues. Thus, in addition to functioning as markers in prostate cancer detection, humoral response profiles can serve as powerful tools revealing pathway dysregulation that might otherwise be suppressed by the complexity of the cancer proteome. Molecular & Cellular Proteomics 7:600 -611, 2008.Although prostate carcinoma is the leading cancer diagnosis in American men, its early detection facilitates effective treatment modalities and improved mortality (1). Although the advent of prostate-specific antigen (PSA) 1 screening has led to earlier detection of prostate cancers (2), its lack of specificity for neoplasm has resulted in a dramatic increase in the number of subsequent prostate needle biopsies (3). As the population of men 65 years and older is expected to increase from 14 million in the year 2000 to 31 million by 2030 (4), it will be increasingly important to distinguish men with benign prostatic hyperplasia from those having neoplastic disease warranting clinical intervention. Thus, there is a compelling need to define additional clinical markers for accurate detection of prostate cancers.This situation has spawned a wide range of serum-based early detection methodologies, including protein microarrays (5). Complicating this approach is the fact that potentially viable tumor biomarkers are embedded among a bounty of proteomic noise. This noise includes housekeeping and other highly abundant proteins, whereas the relatively low abun...

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“…However, 28-47% of transrectal ultrasound (TRUS)-guided prostate biopsies do not detect a present PCA (false negatives), and up to one-third of patients were upgraded to higher GS from biopsy to prostatectomy specimen (4,8,9).…”

Section: Introductionmentioning

confidence: 99%

The value of ADC, T2 signal intensity, and a combination of both parameters to assess Gleason score and primary Gleason grades in patients with known prostate cancer

et al. 2014

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Background: The ability to non-invasively analyze tumor aggressiveness is an important predictor for individual treatment stratification and patient outcome in prostate cancer (PCA). Purpose: To evaluate: (i) whether apparent diffusion coefficient (ADC), the T2 signal intensity (SI), and a combination of both parameters allow for an improved discrimination of Gleason Score (GS) !7 (intermediate and high risk) and GS <7 (low risk) in PCA; and (ii) whether ADC may distinguish between 3 þ 4 and 4 þ 3 PCA (primary Gleason grades [pGG]). Material and Methods: Prostatectomy specimens of 66 patients (mean age, 63 AE 5.6 years; 104 PCA foci) with a preceding multiparametric 1.5 T endorectal coil magnetic resonance imaging (MRI) were included. ADC (b values ¼ 0, 100, 400, 800 s/mm 2 ), standardized T2 (T2s), and the ADC/T2s ratio were tested for correlation with GS applying multivariate analysis. ADC cutoff values were calculated for prediction of GS and pGG, and logarithm of the odds (LOGIT) was used to express the probability for GS and pGG. Diagnostic accuracy was assessed by ROC analysis. Results: We found an almost linear negative relationship of ADC for GS !7 (P ¼ 0.002). The effect of ADC for GS !7 (adjusted odds ratio ¼ 0.995) was almost identical for peripheral and transition zone PCA (P ¼ 0.013 and P < 0.001, respectively). ADC showed an AUC of 78.9% for discrimination between GS <7 and GS !7. An ADC cutoff of <1.005 Â 10 À3 mm 2 /s indicated a GS !7 (90.5% sensitivity, 62.5% specificity). Within the group of GS ¼ 7 PCA, an ADC > 0.762 Â 10 À3 mm 2 /s indicated a pGG of 3 (AUC ¼ 69.6%). Conclusion: T2s and the ADC/T2s ratio do not provide additional information regarding prediction of GS. ADC values have a good discriminatory power to distinguish tumors with GS !7 from GS <7 and to predict pGG in GS ¼ 7 PCA.

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Characterization of Prostate Cancer Missed by Sextant Biopsy

Cited by 28 publications

References 21 publications

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

Humoral Response Profiling Reveals Pathways to Prostate Cancer Progression

The value of ADC, T2 signal intensity, and a combination of both parameters to assess Gleason score and primary Gleason grades in patients with known prostate cancer

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