Detection and Clinical Significance of Circulating Cancer Cells in Patient Undergoing Radical Cystectomy

NCT02345473 | Completed DMC

• 1 other identifier: 4186
• Study Type: observational
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Very few factors may be identified as prognostic for patients with bladder cancer undergoing radical cystectomy. Recently, detection of circulating tumor cells has shown to be very promising in anticipating both the likelyhood of distant metastases and survival in patients with breast cancer, melanoma, prostate cancer and other malignancies. In the present study we both tested the detection rate of circulating tumor cells using a PCR based methodology in the peripheral blood of patients undergoing radical cystectomy, and we further correlated our results with their clinical outcome.

Conditions

Bladder Cancer; Circulating Tumor Cells

Keywords

Bladder cancer; Circulating cancer cells

Outcome Measures

Primary Outcomes (1)

• Prevalence of circulating tumor cells

  This outcome measure reflects the exact number of subjects diagnosed with circulating tumor cells within the total population of subjects included in the study

  8 years

Secondary Outcomes (1)

• Overall survival

  8 years

Study Arms (2)

Cystectomy patients

Arm of patients undergoing radical cystectomy for bladder cancer providing peripheral blood samples for detection of circulating cancer cells

Genetic: Detection of circulating tumor cells in blood samples

Healthy volunteers

Arm of healthy subjects not undergoing radical cystectomy providing peripheral blood samples for detection of circulating cancer cells

Genetic: Detection of circulating tumor cells in blood samples

Interventions

Detection of circulating tumor cells in blood samples GENETIC

Ficoll based isolation of mononuclear cells from the peripheral blood of patients undergoing radical cystectomy, nucleic acids extraction and, finally, PCR based detection of sequences specific to cytokeratins.

Cystectomy patients; Healthy volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing radical cystectomy for bladder cancer and healthy volunteers

You may qualify if:

• Prior trans urethral resection of the bladder (TUR)
• Histological confirmation of a transitional cell carcinoma (TCC) of the bladder
• ECOG Performance Status ≤ 2
• WBC count ≥4,000/μL; platelet count ≥150,000/μL; creatinine ≤1.8 mg/dL; AST, ALT, and alkaline phosphatase ≤2X the upper limit of normal, normal total bilirubin
• recent (within 6 weeks of cystectomy) total body CT imaging study excluding distant metastases as well as upper urinary tract TCC

You may not qualify if:

• Neo-adjuvant chemotherapy (either planned or already performed)
• Patients receiving investigational medications
• Subjects not suitable for a radical cystectomy
• Patients not willing to participate

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari: lead

Study Sites (1)

Vincenzo Pagliarulo

Bari, Italy, 70124, Italy

Location

Related Publications (14)

• Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, Skinner E, Bochner B, Thangathurai D, Mikhail M, Raghavan D, Skinner DG. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001 Feb 1;19(3):666-75. doi: 10.1200/JCO.2001.19.3.666.

  PMID: 11157016 BACKGROUND

• Steven K, Poulsen AL. Radical cystectomy and extended pelvic lymphadenectomy: survival of patients with lymph node metastasis above the bifurcation of the common iliac vessels treated with surgery only. J Urol. 2007 Oct;178(4 Pt 1):1218-23; discussion 1223-4. doi: 10.1016/j.juro.2007.05.160. Epub 2007 Aug 14.

  PMID: 17698113 BACKGROUND

• Madersbacher S, Hochreiter W, Burkhard F, Thalmann GN, Danuser H, Markwalder R, Studer UE. Radical cystectomy for bladder cancer today--a homogeneous series without neoadjuvant therapy. J Clin Oncol. 2003 Feb 15;21(4):690-6. doi: 10.1200/JCO.2003.05.101.

  PMID: 12586807 BACKGROUND

• Lotan Y, Gupta A, Shariat SF, Palapattu GS, Vazina A, Karakiewicz PI, Bastian PJ, Rogers CG, Amiel G, Perotte P, Schoenberg MP, Lerner SP, Sagalowsky AI. Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol. 2005 Sep 20;23(27):6533-9. doi: 10.1200/JCO.2005.05.516. Epub 2005 Aug 22.

  PMID: 16116151 BACKGROUND

• Attard G, Swennenhuis JF, Olmos D, Reid AH, Vickers E, A'Hern R, Levink R, Coumans F, Moreira J, Riisnaes R, Oommen NB, Hawche G, Jameson C, Thompson E, Sipkema R, Carden CP, Parker C, Dearnaley D, Kaye SB, Cooper CS, Molina A, Cox ME, Terstappen LW, de Bono JS. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 2009 Apr 1;69(7):2912-8. doi: 10.1158/0008-5472.CAN-08-3667.

  PMID: 19339269 BACKGROUND

• Marrinucci D, Bethel K, Bruce RH, Curry DN, Hsieh B, Humphrey M, Krivacic RT, Kroener J, Kroener L, Ladanyi A, Lazarus NH, Nieva J, Kuhn P. Case study of the morphologic variation of circulating tumor cells. Hum Pathol. 2007 Mar;38(3):514-9. doi: 10.1016/j.humpath.2006.08.027. Epub 2006 Dec 22.

  PMID: 17188328 BACKGROUND

• Desgrandchamps F, Teren M, Dal Cortivo L, Marolleau JP, Bertheau P, Villette JM, Cortesse A, Teillac P, Le Duc A, Hamdy FC. The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer. Br J Cancer. 1999 Nov;81(5):832-4. doi: 10.1038/sj.bjc.6690771.

  PMID: 10555753 BACKGROUND

• Osman I, Kang M, Lee A, Deng FM, Polsky D, Mikhail M, Chang C, David DA, Mitra N, Wu XR, Sun TT, Bajorin DF. Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients. Int J Cancer. 2004 Oct 10;111(6):934-9. doi: 10.1002/ijc.20366.

  PMID: 15300806 BACKGROUND

• Ribal MJ, Mengual L, Marin M, Algaba F, Ars E, Fernandez PL, Oliva R, Villavicencio H, Alcaraz A. Molecular staging of bladder cancer with RT-PCR assay for CK20 in peripheral blood, bone marrow and lymph nodes: comparison with standard histological staging. Anticancer Res. 2006 Jan-Feb;26(1A):411-9.

  PMID: 16475726 BACKGROUND

• Jiang J, Ulbright TM, Younger C, Sanchez K, Bostwick DG, Koch MO, Eble JN, Cheng L. Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. Arch Pathol Lab Med. 2001 Jul;125(7):921-3. doi: 10.5858/2001-125-0921-CACIPU.

  PMID: 11419977 BACKGROUND

• Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000 Sep;13(9):962-72. doi: 10.1038/modpathol.3880175.

  PMID: 11007036 BACKGROUND

• Wu XR, Lin JH, Walz T, Haner M, Yu J, Aebi U, Sun TT. Mammalian uroplakins. A group of highly conserved urothelial differentiation-related membrane proteins. J Biol Chem. 1994 May 6;269(18):13716-24.

  PMID: 8175808 BACKGROUND

• Wu X, Kakehi Y, Zeng Y, Taoka R, Tsunemori H, Inui M. Uroplakin II as a promising marker for molecular diagnosis of nodal metastases from bladder cancer: comparison with cytokeratin 20. J Urol. 2005 Dec;174(6):2138-42, discussion 2142-3. doi: 10.1097/01.ju.0000181214.32390.75.

  PMID: 16280744 BACKGROUND

• Sawabata N, Okumura M, Utsumi T, Inoue M, Shiono H, Minami M, Nishida T, Sawa Y. Circulating tumor cells in peripheral blood caused by surgical manipulation of non-small-cell lung cancer: pilot study using an immunocytology method. Gen Thorac Cardiovasc Surg. 2007 May;55(5):189-92. doi: 10.1007/s11748-007-0101-2.

  PMID: 17554991 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplastic Cells, Circulating

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Vincenzo VP Pagliarulo, Urologist

  Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: January 26, 2015
• Study Start: January 1, 2005
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: January 26, 2015

Record last verified: 2015-01

Locations

IT (1)