Transitional cell carcinoma

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Transitional cell carcinoma
Other namesUrothelial carcinoma
Bladder urothelial carcinoma (1) pT1.JPG
Histopathology of transitional carcinoma of the urinary bladder. Transurethral biopsy. Hematoxylin and eosin stain.
Specialty Oncology

Transitional cell carcinoma, also called urothelial carcinoma, is a type of cancer that typically occurs in the urinary system. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. Symptoms of urothelial carcinoma in the bladder include hematuria (blood in the urine). Diagnosis includes urine analysis and imaging of the urinary tract (cystoscopy). Transitional cell carcinomas arise from the transitional epithelium, a tissue lining the inner surface of these hollow organs. [1] When the term "urothelial" is used, it specifically refers to a carcinoma of the urothelium, meaning a transitional cell carcinomas of the urinary system.

Contents

It accounts for 95% of bladder cancer cases and bladder cancer is in the top 10 most common malignancy disease in the world and is associated with approximately 200,000 deaths per year in the US. [2] [3] It is the second most common type of kidney cancer, but accounts for only five to 10 percent of all primary renal malignant tumors. [4] Men and older people have a higher rate of urothelial carcinomas. Other risk factors include smoking and exposure to aromatic amines. [5]

Treatment approaches depend on the stage and spread of the tumour. Tumour removal (resection), chemotherapy and chemoradiation may be indicated. Immunotherapy with immune check point inhibitor medications may also be suggested. [5]

Signs and symptoms

Signs and symptoms of transitional cell carcinomas depend on the location and extent of the cancer. Symptoms of bladder cancer is blood in the urine. [5]

Causes

Urothelial carcinoma is a prototypical example of a malignancy arising from environmental carcinogenic influences. By far the most important cause is cigarette smoking, which contributes to approximately one-half of the disease burden. [6] Chemical exposure, such as those sustained by workers in the petroleum industry, the manufacture of paints and pigments (e.g., aniline dyes), [5] and agrochemicals are known to predispose one to urothelial cancer. [6] The risk is lowered by increased liquid consumption, presumably as a consequence of increased urine production and thus less dwell time on the urothelial surface. Conversely, risk is increased among long-haul truck drivers and others in whom long urine dwell-times are encountered. As with most epithelial cancers, physical irritation has been associated with increased risk of malignant transformation of the urothelium. Thus, urothelial carcinomas are more common in the context of chronic urinary stone disease, chronic catheterization (as in patients with paraplegia or multiple sclerosis), and chronic infections. Some particular examples are listed below:

  1. Certain drugs, such as cyclophosphamide, via the metabolites acrolein and phenacetin, may predispose to the development of transitional cell carcinomas (the latter especially with respect to the upper urinary tract). [7]
  2. Radiation exposure
  3. Somatic mutation, such as deletion of chromosome 9q, 9p, 11p, 17p, 13q, 14q and overexpression of RAS (oncogene) and epidermal growth factor receptor (EGFR).[ citation needed ]
  4. Presence of an abnormal extra chromosome, classified as a small supernumerary marker chromosome (sSMC), in this malignancy's tumor cells.[ citation needed ] The sSMC has an isochromosome-like structure consisting of two copies of the short (i.e. p) arm of chromosome 5. In consequence, the malignant cells bearing it have four copies of this p arm's genetic material, two from each of the normal chromosome 5's and two from the sSMC. [8] "sSMC i(5)(p10)" is the single most common recurrent structural chromosomal abnormality in transitional cell carcinoma, being present in its malignant cells in most cases of the disease. Transitional cell bladder carcinomas associated with this sSMS are more aggressive and invasive than those not associated with it. [9]

Growth and spread

Transitional cell carcinomas are often multifocal, with 30–40% of patients having more than one tumor at diagnosis. The pattern of growth of transitional cell carcinomas can be papillary, sessile, or carcinoma in situ. The most common site of transitional cell carcinoma metastasis outside the pelvis is bone (35%); of these, 40 percent are in the spine. [10]

Diagnosis

Bladder diverticula containing stones. The bladder wall is thickened due to possible transitional cell carcinoma. BladderdiverticuliwithstoneMark.png
Bladder diverticula containing stones. The bladder wall is thickened due to possible transitional cell carcinoma.
The Paris System for reporting urinary cytology, version 2.0, ranging from negative to positive for high grade urothelial carcinoma (HGUC). The Paris System for reporting urinary cytology 2.0.png
The Paris System for reporting urinary cytology, version 2.0, ranging from negative to positive for high grade urothelial carcinoma (HGUC).

Transitional refers to the histological subtype of the cancerous cells as seen under a microscope.

Immunohistochemistry for p53 can help distinguish a PUNLMP from a low grade urothelial carcinoma. Overexpression is seen in 75% of low-grade urothelial carcinomas and only 10% of PUNLMP. Expression of p53 in urothelial neoplasms.png
Immunohistochemistry for p53 can help distinguish a PUNLMP from a low grade urothelial carcinoma. Overexpression is seen in 75% of low-grade urothelial carcinomas and only 10% of PUNLMP.

Classification

Transitional cell carcinomas are mostly papillary (70%, [2] and 30% non-papillary). [2]

The 1973 WHO grading system for transitional cell carcinomas (papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO [14] grading for papillary types (papillary neoplasm of low malignant potential [PNLMP], low grade, and high grade papillary carcinoma). High-grade carcinoma typically displays more pleomorphism, multiple mitoses, euchromatin and relatively prominent nucleoli, and uneven distribution of nuclei.

Treatment

Localized/early transitional cell carcinomas of bladder

Transitional cell carcinomas can be very difficult to treat. Treatment for localized stage transitional cell carcinomas is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) or a few weeks after the surgery as a six dose regimen.

Localized/early transitional cell carcinomas can also be treated with infusions of Bacille Calmette–Guérin into the bladder. These are given weekly for either 6 weeks (induction course) or 3 weeks (maintenance/booster dose). Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to BCG, causing severe intolerance and a possible reduction in bladder volume due to scarring.

In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.

Advanced or metastatic transitional cell carcinomas

First-line chemotherapy regimens for advanced or metastatic transitional cell carcinomas consists of gemcitabine and cisplatin) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC polychemotherapy). [15] The side effects associated with some of these polychemotherapy treatment options are considered serious and mortality from MVAC treatment has been estimated at approximately 4%. [5] Cisplatin and gemcitabine treatment may be associated with less severe side effects. [5] Up to half of people with bladder cancer are not able to take these chemotherapy treatments due to their overall health.

Taxanes or vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy). [16]

Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC, however this is based on low certainty evidence. [17] [5]

In May 2016, the FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. [18] The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival. [19]

In April 2021, the FDA granted accelerated approval to sacituzumab govitecan for people with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor. [20]

Prostate

Transitional cell carcinomas can also be associated with the prostate. [21] [22]

See also

Related Research Articles

<span class="mw-page-title-main">Bladder cancer</span> Urinary system cancer that begins in the urinary bladder

Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become malignant.

<span class="mw-page-title-main">Kidney cancer</span> Medical condition

Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, a lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include spread to the lungs or brain.

<span class="mw-page-title-main">Small-cell carcinoma</span> Type of malignant cancer

Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma is more aggressive, with a shorter doubling time, higher growth fraction, and earlier development of metastases.

<span class="mw-page-title-main">Transitional epithelium</span> A type of tissue

Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching. The transitional epithelium usually appears cuboidal when relaxed and squamous when stretched. This tissue consists of multiple layers of epithelial cells which can contract and expand in order to adapt to the degree of distension needed. Transitional epithelium lines the organs of the urinary system and is known here as urothelium. The bladder, for example, has a need for great distension.

<span class="mw-page-title-main">Mitomycin C</span> Chemical compound

Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity.

Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.

<span class="mw-page-title-main">Non-small-cell lung cancer</span> Any type of epithelial lung cancer other than small-cell lung carcinoma

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<span class="mw-page-title-main">Urethral cancer</span> Medical condition

Urethral cancer is a rare cancer originating from the urethra. The disease has been classified by the TNM staging system and the World Health Organization.

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<span class="mw-page-title-main">Papillary urothelial neoplasm of low malignant potential</span> Medical condition

Papillary urothelial neoplasm of low malignant potential (PUNLMP) is an exophytic, (microscopically) nipple-shaped pre-malignant growth of the lining of the upper genitourinary tract, which includes the renal pelvis, ureters, urinary bladder and part of the urethra.

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<span class="mw-page-title-main">Ureteral cancer</span> Medical condition

Ureteral cancer is cancer of the ureters, muscular tubes that propel urine from the kidneys to the urinary bladder. It is also known as ureter cancer, renal pelvic cancer, and rarely ureteric cancer or uretal cancer. Cancer in this location is rare. Ureteral cancer becomes more likely in older adults, usually ages 70–80, who have previously been diagnosed with bladder cancer.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

Dr. Cora Sternberg is an American medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital, serving as a member of the Genitourinary (GU) Oncology Program. Dr. Sternberg facilitates the continued growth and development of clinical and translational research programs in GU malignancies. Dr. Sternberg is an internationally respected leader in the field of medical oncology and urological malignancies and a recognized expert in the area of new drug development. She is known for her seminal contributions in bladder cancer, her strong track record of sustained genito-urinary (GU) oncology leadership and collaboration in multiple practice-changing clinical trials, including novel medicines, and her current role applying her expertise in oncology and GU cancers to precision medicine to further improve outcomes for patients. Dr. Sternberg has been decidedly influential in the development of novel hormonal therapies and checkpoint inhibitors across the landscape of GU oncology as evidenced in her curriculum vitae. She is a globally respected researcher who has lectured extensively at universities and cancer symposia worldwide (>800). As Clinical Director of the Englander Institute for Precision Medicine (EIPM), Dr. Sternberg develops strategies to incorporate genomic sequencing and precision medicine throughout the Weill Cornell Medicine and NewYork-Presbyterian healthcare network, including Lower Manhattan, Brooklyn and Queens.

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References

  1. ↑ "transitional cell carcinoma" "at Dorland's Medical Dictionary
  2. 1 2 3 Andreassen BK, Aagnes B, Gislefoss R, Andreassen M, Wahlqvist R (October 2016). "Incidence and Survival of urothelial carcinoma of the urinary bladder in Norway 1981-2014". BMC Cancer. 16 (1): 799. doi: 10.1186/s12885-016-2832-x . PMC   5064906 . PMID   27737647.
  3. ↑ "Types of Bladder Cancer: TCC & Other Variants". CancerCenter.com. Retrieved 2018-08-10.
  4. ↑ "Kidney Cancer - Introduction". Cancer.Net. 2012-06-25. Retrieved 2019-12-02.
  5. 1 2 3 4 5 6 7 Maisch, Philipp; Hwang, Eu Chang; Kim, Kwangmin; Narayan, Vikram M; Bakker, Caitlin; Kunath, Frank; Dahm, Philipp (2023-10-09). Cochrane Urology Group (ed.). "Immunotherapy for advanced or metastatic urothelial carcinoma". Cochrane Database of Systematic Reviews. 2023 (10). doi:10.1002/14651858.CD013774.pub2. PMC   10561349 . PMID   37811690.
  6. 1 2 "Bladder Cancer Risk Factors | Risk for Bladder Cancer". www.cancer.org. Retrieved 2023-10-14.
  7. ↑ Colin P, Koenig P, Ouzzane A, Berthon N, Villers A, Biserte J, Rouprêt M (November 2009). "Environmental factors involved in carcinogenesis of urothelial cell carcinomas of the upper urinary tract". BJU International. 104 (10): 1436–1440. doi:10.1111/j.1464-410X.2009.08838.x. PMID   19689473.
  8. ↑ Jafari-Ghahfarokhi H, Moradi-Chaleshtori M, Liehr T, Hashemzadeh-Chaleshtori M, Teimori H, Ghasemi-Dehkordi P (2015). "Small supernumerary marker chromosomes and their correlation with specific syndromes". Advanced Biomedical Research. 4: 140. doi: 10.4103/2277-9175.161542 . PMC   4544121 . PMID   26322288.
  9. ↑ Fadl-Elmula I (August 2005). "Chromosomal changes in uroepithelial carcinomas". Cell & Chromosome. 4: 1. doi: 10.1186/1475-9268-4-1 . PMC   1199610 . PMID   16083510.
  10. ↑ Punyavoravut V, Nelson SD (August 1999). "Diffuse bony metastasis from transitional cell carcinoma of urinary bladder: a case report and review of literature". Journal of the Medical Association of Thailand = Chotmaihet Thangphaet. 82 (8): 839–843. PMID   10511795.
  11. ↑ - Image by Mikael Häggström. Reference: Wojcik, EM; Kurtycz, DFI; Rosenthal, DL (2022). "We'll always have Paris The Paris System for Reporting Urinary Cytology 2022". J Am Soc Cytopathol. 11 (2): 62–66. doi:10.1016/j.jasc.2021.12.003. PMID   35094954. S2CID   246429500.
  12. ↑ Image is taken from following source, with some modification by Mikael Häggström, MD:
    - Schallenberg S, Plage H, Hofbauer S, Furlano K, Weinberger S, Bruch PG; et al. (2023). "Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors". Acta Oncol: 1–10. doi: 10.1080/0284186X.2023.2277344 . PMID   37938166.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ↑ Source for role in distinguishing PUNLMP from low-grade carcinoma:
    - Kalantari MR, Ahmadnia H (2007). "P53 overexpression in bladder urothelial neoplasms: new aspect of World Health Organization/International Society of Urological Pathology classification". Urol J. 4 (4): 230–3. PMID   18270948.
  14. ↑ Sauter G, Algaba F, Amin MB, Busch C, Cheville J, Gasser T, Grignon D, Hofstaedter F, Lopez-Beltran A, Epstein JI. Noninvasive urothelial neoplasias: WHO classification of noninvasive papillary urothelial tumors. In World Health Organization classification of tumors. Pathology and genetics of tumors of the urinary system and male genital organs. Eble JN, Epstein JI, Sesterhenn I (eds): Lyon, IARCC Press, p. 110, 2004
  15. ↑ von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. (September 2000). "Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study". Journal of Clinical Oncology. 18 (17): 3068–3077. doi: 10.1200/jco.2000.18.17.3068 . PMID   11001674. S2CID   21471159.
  16. ↑ Immunotherapy Proceeds to Change Bladder Cancer Treatment 2017
  17. ↑ Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID   29208439.
  18. ↑ "FDA approves new, targeted treatment for bladder cancer". FDA. 18 May 2016. Retrieved 20 May 2016.
  19. ↑ Failed confirmatory trial raises questions about atezolizumab for advanced urothelial cancer. June 2017
  20. ↑ "FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer". U.S. Food and Drug Administration (FDA). 13 April 2021. Retrieved 13 April 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  21. ↑ Walsh DL, Chang SS (2009). "Dilemmas in the treatment of urothelial cancers of the prostate". Urologic Oncology. 27 (4): 352–357. doi:10.1016/j.urolonc.2007.12.010. PMID   18439852.
  22. ↑ Njinou Ngninkeu B, Lorge F, Moulin P, Jamart J, Van Cangh PJ (January 2003). "Transitional cell carcinoma involving the prostate: a clinicopathological retrospective study of 76 cases". The Journal of Urology. 169 (1): 149–152. doi:10.1016/S0022-5347(05)64056-6. PMID   12478124.
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