Cancer Treatment

Predictive tests for shunting normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, dementia, and/or urinary incontinence without causative disorders, and ventricular enlargement due to disturbance of the cerebrospinal fluid (SF) circulation. Surgical CSF shunting remains the main treatment modality. Prior to embarking upon surgical therapy, knowing which patients may benefit from surgery. Several different tests can be performed to predict success from shunting. While large volume lumbar puncture was the earliest invasive diagnostic test in predicting response to shunt surgery, external lumbar drainage (ELD) is being used with increased frequency, followed by shunting. The review by Burnett, questions to to to of any predictive test.

 Ishikawa M; Guideline Committe for Idiopathic Normal Pressure Hydrocephalus, Clinical guidelines for idiopathic normal pressure hydrocephalus.
Neurol Med Chir (Tokyo). 2004 Apr;44(4):222-3.

Tsakanikas D, Relkin N. Normal pressure hydrocephalus. Semin Neurol. Feb 2007;27(1):58-65.

Burnett MG, Sonnad SS, Stein SC. Screening tests for normal-pressure hydrocephalus: sensitivity, specificity, and cost. J Neurosurg. Dec 2006;105(6):823-9.

Urine PCA3

The widely used PSA blood marker is well established. However, the poor specificity of the PSA test for detecting cancer, or for differentiating indolent cancers from clinically significant ones, tends to lead to many negative biopsies and overtreatment of men with prostatic adenocarcinoma. More specific markers are being sought.PCA3 (formerly known as DD3) is one such marker. It is a prostate-tissue-specific, noncoding messenger RNA (mRNA) that is selectively overexpressed in virtually all prostate carcinoma specimens compared to normal prostate tissue. These attributes of PCA3 mRNA expression make it a promising prostate-cancer-specific marker. The potential of the prostate cancer antigen 3 (PCA3) urine assay to aid prostate cancer diagnosis and minimize unnecessary biopsies has been extensively studied. Results from three recent studies that compared the performance of PCA3 with PSA are promising but some issues remain. For example, it is not known what the most appropraite cutoff might be for optimal decision making for or against biopsy. At this time, it is not recommended by any guidelines to my knowledge.

Chun FK, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PFA, Huland H, Abbou C-C, Stillebroer AB, van Gils MPMQ, Schalken JA, Fradet Y, Marks LS, Ellis W, Partin AW, Hease A.Prostate Cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram,  Eur Urol 2009;56:659-67

Scott A. Tomlins et al, Urine TMPRSS2:ERG Fusion Transcript Stratifies Prostate Cancer Risk in Men with Elevated Serum PSA Sci Transl Med 3 August 2011: Vol. 3, Issue 94, p. 94ra72

Ploussard, G. & de la Taille, A. Urine biomarkers in prostate cancer. Nat. Rev. Urol. 7, 101–109 (2010).

Day, J. R., Jost, M., Reynolds, M. A., Groskopf, J. & Rittenhouse, H. PCA3: from basic molecular science to the clinical lab. Cancer Lett. 301, 1–6 (2011).

Ploussard, G. et al. The prostate cancer gene 3 (PCA3) urine test in men with previous negative biopsies: does free-to-total prostate-specific antigen ratio influence the performance of the PCA3 score in predicting positive biopsies? BJU Int. 106, 1143–1147 (2010).

.Auprich, M. et al. External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome. Eur. Urol. 58, 727–732 (2010).

Roobol, M. J. et al. Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test. Eur. Urol. 58, 475–481 (2010).

Haese, A. et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur. Urol. 54, 1081–1088 (2008).

Marks, L. S. et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 69, 532–535 (2007).