Medical Student Research Fellowship for Summer 2010
Mentor: Yair Lotan
Room number: J8.112
Mail Code: 9110
Phone number: 8-0389
Project title: Prospective Evaluation of the Role of Molecular Marker Alterations to Predict Outcomes of Patients with Non-invasive Bladder Cancer
Human subjects IRB approved project number (where applicable): IRB 0503-307
Animal subjects IRB approved project number (where applicable):
Project Type - Patient-based research
Brief Description of Project:
Urothelial carcinoma of the bladder (UCB) is the 4th most common cancer in men and the 5th most common cancer overall. Up to 70% to 80% of patients diagnosed with UCB present with either gross or microscopic hematuria, and muscle invasion is present in 25% of patients at diagnosis. Overall UCB survival rates are stage dependent and 5-year survival for tumors confined to the mucosa (90%) are significantly higher than for cancers that are muscle invasive (40%) or metastatic (less than 30%). Unfortunately, despite successful treatment, 50%-70% of these tumors will recur within 5 years and 10%-30% will progress to invasive cancer. A major limitation of current TNM criteria and nomograms is that tumors of a similar stage and grade can have significantly different biology and metastatic potential. The integration of information regarding molecular alterations and differences in tumor biology has the potential to further improve the accuracy of predictive models.
A variety of key molecules have been associated with disease recurrence and progression of UCB, thereby representing candidate markers likely to improve prognostic accuracy. Altered expression levels of cell-cycle regulators (e.g. p53, p21, p27, ki67 and cyclin E) are the predominant characteristics of malignant UCB cells. Molecular biomarker research in UCB has also focused on increased cell proliferation, signal transduction pathways, apoptosis, tumor cell growth, tumor cell migration and invasion through extracellular matrix modulating molecules, and (lymph)angiogenesis. We have previously published multiple studies evaluating the role of molecular markers on outcomes of non-muscle invasive bladder cancers. This study is a prospective evaluation of 3 year outcomes for patients who were treated with non-invasive high grade bladder cancer at our institution. The goal is to validate prior studies which were retrospective in nature. We predict that tumor with multiple molecular alterations will have worse outcomes than tumors of similar stage and few alterations. We will review outcomes in this prospectively collected group of patients. Since January 2007, every patient with high grade bladder cancer had staining for a panel of 5 molecular markers (p53, p21, p27, cyclin E and Ki-67). The plan for the student is to perform a chart review to correlate marker status with patient outcomes.
1. Shariat SF, Bolenz C, Godoy G, Fradet Y, Ashfaq R, Karakiewicz PI, Isbarn
H, Jeldres C, Rigaud J, Sagalowsky AI, Lotan Y. Predictive Value of Combined
Immunohistochemical Markers in Patients With pT1 Urothelial Carcinoma at Radical
Cystectomy. J Urol. 2009 Jul;182(1):78-84; discussion 84. Epub 2009 May 17.
2. Shariat SF, Ashfaq R, Sagalowsky AI and Lotan Y (2007) Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. Urol Oncol 25: 468-75
3. Karam JA, Lotan Y, Ashfaq R, Sagalowsky AI, Shariat SF. Survivin expression in patients with non-muscle-invasive urothelial cell carcinoma of the bladder. Urology 2007 Sep;70(3):482-6.
4. Shariat SF, Zlotta AR, Ashfaq R, Sagalowsky AI, Lotan Y. Cooperative effect of cell- cycle regulators expression on bladder cancer development and biologic aggressiveness. Modern Pathology. 2007 Apr; 20(4): 445-459.
5. Margulis V, Shariat SF, Ashfaq R, Thompson M, Sagalowsky AI, Hsieh JT, Lotan Y. Expression of cyclooxygenase-2 in normal urothelium, and superficial and advanced transitional cell carcinoma of bladder. J Urol. 2007 Mar;177(3):1163-8.
Previous Research Activities or Publications with Medical Students:
6. Bolenz C, Gupta A, Hotze T, Ho R, Cadeddu JA, Roehrborn CG, Lotan Y. Cost
Comparison of Robotic, Laparoscopic, and Open Radical Prostatectomy for Prostate
Cancer. Eur Urol. 2009 Nov 11. [Epub ahead of print]PMID: 19931979
7. Schlomer BJ, Ho R, Sagalowsky A, Ashfaq R, Lotan Y. Prospective Validation of the Clinical Usefulness of Reflex Fluorescence In Situ Hybridization Assay in Patients With Atypical Cytology for the Detection of Urothelial Carcinoma of the Bladder. J Urol. 2009 Nov 12. [Epub ahead of print]PMID: 19913822
8. Raman JD, Bagrodia A, Bensalah K, Pearle MS, Lotan Y. Residual Fragments After Percutaneous Nephrolithotomy: Cost Comparison of Immediate Second Look Flexible Nephroscopy Versus Expectant Management. J Urol. 2009 Nov 12. [Epub ahead of print]PMID: 19913809
9. Lotan Y, Bolenz C, Gupta A, Hotze T, Ho R, Cadeddu JA, Roehrborn CG. The effect of the approach to radical prostatectomy on the profitability of hospitals and surgeons. BJU Int. 2009 Oct 28. [Epub ahead of print]PMID: 19874301
10. Bensalah K, Tuncel A, Raman JD, Bagrodia A, Pearle M, Lotan Y. How Physician and Patient Perceptions Differ Regarding Medical Management of Stone Disease. J Urol. 2009 Jul 17. [Epub ahead of print]. PMID: 19616801.
11. Bagrodia A, Gupta A, Raman JD, Bensalah K, Pearle MS, Lotan Y. Predictors of Cost and Clinical Outcomes of Percutaneous Nephrostolithotomy. J Urol. 2009 Aug;182(2):586-90. Epub 2009 Jun 17. PMID: 19535106.
12. Lotan Y, Elias K, Svatek RS, Bagrodia A, Nuss G, Moran B, Sagalowsky AI. Bladder Cancer Screening in a High Risk Asymptomatic Population Using a Point of Care Urine Based Protein Tumor Marker. J Urol. 2009 Jul;182(1):52-7; discussion 58. Epub 2009 May 17.PMID: 19450825.
13. Bagrodia A, Grover S, Srivastava A, Gupta A, Bolenz C, Sagalowsky AI, Lotan Y. Impact of body mass index on clinical and cost outcomes after radical cystectomy. BJU Int. 2009 Feb 9. [Epub ahead of print].
14. Raman JD, Bagrodia A, Gupta A, Bensalah K, Cadeddu JA, Lotan Y, Pearle MS. Natural history of residual fragments following percutaneious nephrostolithotomy. J Urol. 2009 Mar; 181(3):1163-8. Epub 2009 Jan 18. PMID: 19152935.
15. Nieder AM, Lotan Y, Nuss GR, Langston JP, Vyas S, Manoharan M, Soloway MS. Are patients with hematuria appropriately referred to Urology? A multi-institutional questionnaire based survey. Urol Oncol. 2008 Dec 19; [Epub ahead of print]. PMID: 19097811.
16. Bagrodia A, Raman JD, Bensalah K, Pearle MS, Lotan Y. Synchronous Bilateral Percutaneous Nephrostolithotomy: Analysis of Clinical Outcomes, Cost and Surgeon Reimbursement. J Urol. 2009 Jan;181(1):149-53. Epub 2008 Nov 13. PMID: 19012904.
17. Bagrodia A, Gupta A, Raman JD, Bensalah K, Pearle MS, Lotan Y. Impact of body mass index on cost and clinical outcomes after percutaneous nephrostolithotomy. Urology. 2008 Oct;72(4);756-60. Epub 2008 Aug 2. PMID: 18718645.
18. Lotan Y, Bagrodia A, Roehrborn CG, Scott J. Are urologists fairly reimbursed for complex procedures: failure of 22 modifier? Urology. 2008 Sep;72(3):494-7. Epub 2008 Jul 2. PMID: 18597834.
19. Lotan Y, Bensalah K, Ruddell T, Shariat SF, Sagalowsky AI, Ashfaq R. Prospective Evaluation of the clinical usefulness of reflex fluorescence in situt hybridization assay in patients with atypical cytology for the detection of urothelial carcinoma of the bladder. J Urol. 2008 Jun; 179(6):2164-9. Epub 2008 Apr 18. PMID: 18423745.
20. Bensalah K, Raman JD, Bagrodia A, Marvin A, Lotan Y. Does obesity impact the costs of partial and radical nephrectomy? J Urol. 2008 May; 179(5):1714-7; discussion 1718-8. Epub 2008 Mar 17. PMID: 18343428.
21. Lucas SM, Svatek RS, Olgin G, Arriaga Y, Kabbani W, Sagalowsky AI, Lotan Y. Conservative management in selected patients with upper tract urothelial carcinoma compares favourably with early radical surgery. BJU Int. 2008 Jul;102(2):172-6 Epub 2008 Jul 1.
22. Malaeb BS, Rashid HH, Lotan Y, Khoddami SM, Shariat SF, Sagalowsky AI, McConnell JD, Roehrborn CG, Koeneman KS. Prostate cancer disease-free survival after radical retropubic prostatectomy in patients older than 70 years compared to younger cohorts. Urol Oncol. 2007 Jul-Aug;25(4):291-7.
23. Stern JM, Svatek R, Park S, Hermann M, Lotan Y, Sagalowsky AI, Cadeddu JA. Intermediate comparison of partial nephrectomy and radiofrequency ablation for clinical T1a renal tumours. BJU Int. 2007 Aug;100(2):287-90.
24. Shariat SF, Ashfaq R, Karakiewicz PI, Saeedi O, Sagalowsky AI, Lotan Y. Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer. 2007 March 15; 109(6): 1106-1113.
25. Park S, Jaffer O, Lotan Y, Saboorian H, Roehrborn CG, Cadeddu JA. Contemporary laparoscopic and open radical retropubic prostatectomy: pathologic outcomes and Kattan postoperative nomograms are equivalent. Urology. 2007 Jan;69(1):118-22.
26. Svatek RS, Lotan Y, Hermann M, Duchene DA, Sagalowsky AI, Cadeddu JA. The influence of clinical and pathological stage discrepancy on cancer specific survival in patients treated for renal cell carcinoma. J Urol. 2006 Oct;176(4):1321-5.
27. Svatek RS, Herman MP, Lotan Y, Casella R, Hsieh JT, Sagalowsky AI, Shariat SF. Soluble Fas-A promising novel urinary marker for the detection of recurrent superficial bladder cancer. Cancer. 2006 Mar 15.
28. Anderson JK, Murdock A, Cadeddu JA, Lotan Y. Cost Comparison of Laparoscopic versus Radical Retropubic Prostatectomy. Urology. 2005 Sep;66(3):557-60.
29. Svatek RS, Lee D, Lotan Y. Correlation of Office-Based Cystoscopy and Cytology with Histologic Diagnosis: How Good is the Gold Standard? Urology. 2005 Jul;66(1):65-8.
30. Shariat SF, Herman MP, Casella R, Lotan Y, Karam JA, Stenman UH. Urinary Levels of Tumor-Associated Trypsin Inhibitor (TATI) in the Detection of Transitional Cell Carcinoma of the Urinary Bladder. Eur Urol. 2005 Sep;48(3):424-31.
31. Khoddami SM, Shariat SF, Lotan Y, Saboorian H, McConnell JD, Sagalowsky AI, Roehrborn CG, Koeneman KS: Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy. BJU Int. 2004 Jul;94(1):42-6.
32. Lotan Y, Shariat SF, Khoddami SM, Saboorian H, Koeneman KS, Cadeddu JA, Sagalowsky AI, McConnell JD, Roehrborn CG.: The percent of biopsy cores positive for cancer is a predictor of advanced pathologic stage and poor clinical outcomes in patients treated with radical prostatectomy. J Urol. 2004 Jun;171(6, Part 1 Of 2):2209-2214.
33. Shariat SF, Lotan Y, Saboorian H, Khoddami SM, Roehrborn CG, Slawin KM, Ashfaq R.: Survivin expression is associated with features of biologically aggressive prostate cancer. Cancer. 2004 Feb 15;100(4):751-7.