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Stages and Grades of Bladder Cancer

Stages and Grades of Bladder Cancer

Executive Summary

The staging system of bladder cancer depends on the development of cancer cells in the bladder and its metastasis to both inside and outside the bladder. The stages of bladder cancer are determined by examining the sample removed during a TURBT. Invasive and non-invasive cancer is determined by analyzing the staging system. The TNM system is the tool doctors use to describe the stage of Bladder cancer. There are different stage descriptions for each type of cancer. The stages of bladder cancer range from stage 0 to stage IV. The sub-stages of bladder cancer include Stage 0 (Tis, N0, M0), stage I ( T1, N0, M0), stage II (T2(a or b), N0, M0), stage III- IIIA (T3a, T3b, or T4a; N0; M0) and IIIB (T1 to T4a, N2 or N3, M0), stage IV- IVA (T4b, any N, M0 or any T, any N, M1a), IVB (any T, any N, M1b). Staging can be clinical or pathological. The recurrence of cancer staging is also determined by determining the extent of recurrence through restaging. Also, the grading system is integrated for assessing the degree of similarity of cancer cells with healthy cells. The low-grade cancers show similarities to normal bladder cells, and high-grade cancers poorly differentiate for becoming invasive and show metastasis.

Staging System of Bladder Cancer

Staging determines where the tumor is located, whether it has spread or not, and how it grows. While assessing the Stages of Bladder Cancer, many factors are taken into account, including how it is developing in the bladder, where it is growing and has it spread both inside and outside the bladder. In the case of bladder cancer, the stage is determined based on examining the sample removed during a TURBT and finding out whether the cancer has spread to other parts of the body ?1?.

Noninvasive v/s Invasive

Noninvasive indicates that cancer is in the inner layers of the bladder, whereas invasive cancers are deepest in the layer of the bladder wall. If the cancer is said to be superficial or non-muscle invasive, that indicates it is not present in the bladder's main muscle layerthough it may still be invasive or noninvasive and have the potential to spread to the muscle ?2?.

TNM staging system

The TNM system is the tool doctors use to describe the stage of Bladder cancer ?3?.

  • T is for tumor - How large the tumor is and where is its location
  • N is for nodes - Has cancer spread to lymph nodes, and if so, where and how many?
  • M is for metastasis - Whether cancer has metastasized to other body parts distant from the bladder.

There are five stages: stage 0 (zero) and stages I through IV (1 through 4).

Staging can be clinical or pathological. Clinical staging is formed on the results of tests done before surgery. Pathological staging is centred on what is found, depending upon the surgery itself.

Also Read: Symptoms based on Cancer types

T categories for Bladder Cancer

  • TX - The primary tumor cannot be assessed.
  • T0 - No evidence for the primary tumor.
  • Ta - It indicates noninvasive papillary carcinoma. TURBT can easily remove it.
  • Tis - This stage is carcinoma in situ (CIS) or 'flat tumor', which means the cancer is localized or restricted within the urothelium layer of the bladder. It may be called noninvasive cancer or superficial cancer. It can probably come back after treatment.
  • T1 - It indicates that the tumor has grown from layers lining the bladder but has not grown into the muscle layer.
  • T2 - This type has grown into the muscle layer
  • T2a - It indicates tumor in the inner half muscular layer
  • T2b - It indicated tumor in the outer half muscular layer
  • T3 - the tumor has grown into the muscle layer and surrounding fatty tissue that is perivesical tissue.
  • T3a - The spread in fatty tissue can be seen only through a microscope
  • T3b - The tumor is large enough to see macroscopically by imaging tests or seen or felt by a surgeon.
  • T4 - It indicates that a tumor has spread to nearby organs and tissue: abdominal wall, pelvic wall, a man's prostate, or a woman's vagina or uterus.
  • T4a - the tumor has spread to the prostate, seminal vesicles, uterus, or vagina. Surgical removal of the tumor may still be possible in this stage.
  • T4b - The tumor has spread to the pelvic wall or the abdominal wall. Surgical removal of the tumor may not be possible at this stage.

N categories of Bladder cancer

  • NX - It means nearby lymph cannot be evaluated.
  • N0 - It means cancer has not spread to nearby lymph nodes.
  • N1 - It means cancer has spread to one lymph node in the pelvis
  • N2 - It means cancer has spread to 2 or more regional lymph nodes in the pelvis
  • N3 - It means cancer has spread to the common iliac lymph nodes located behind the major arteries in the pelvis

M categories for Bladder cancer

  • M0 - Cancer has not metastasized.
  • M1 - Cancer has spread to distant regions outside the bladder.

Bladder cancer stages

The Stages of Bladder Cancer is determined by combining the results from the TNM system.

Stage 0

  • Stage 0a(Noninvasive papillary carcinoma) - The cancer is found on the surface of the inner lining of cancer. It has not spread to connective tissue or muscle layers.
  • The TNM - Ta, N0, M0.
  • Stage 0is(Flat carcinoma in situ) - The cancer is found only on the bladder's inner lining. It has not grown in the hollow part of the bladder and has not spread to the bladder's connective tissue or thick layer.
  • The TNM - Tis, N0, M0.

Stage 1

Cancer has started growing in the connective tissue of the bladder called lamina propria but has not spread into muscle layers or outside the bladder.

  • The TNM - T1, N0, M0.

Stage 2

Cancer has spread to muscle tissue but not the surrounding fatty tissue and has not spread to lymph nodes or outside the bladder.

  • The TNM -T2(a or b), N0, M0.

Stage 3

  • Stage 3A - Cancer has spread to perivesical tissue or reproductive organs like the uterus, prostate or vagina. The TNM characteristics are (T3a, T3b, or T4a; N0; M0)

Cancer has spread to a single regional lymph node (T1 to T4a, N1, M0).

  • Stage 3B - Cancer has spread to 2 or more regional lymph nodes or the common iliac lymph nodes (T1 to T4a, N2 or N3, M0).

Stage 4

  • Stage 4A - Cancer has spread to the abdominal or pelvic wall or lymph above the main pelvic artery.
  • The TNM -T4b, any N, M0 or any T, any N, M1a.
  • Stage 4B - Cancer has spread to at least one distant organ.
  • The TNM - any T, any N, M1b.

Stages of Bladder Cancer after recurrence

Cancer that returns after the treatment is recurrent cancer. The doctor performs another round of tests to know the extent of recurrence, and this process is called restaging. The new stage has a lowercase "r" in front of it to indicate the recurrence stage.

Grade

Additionally, doctors may talk about the bladder cancer's grade. The grade tells how much cancer cells look like healthy cells when viewed under a microscope.

The regular cells that are grouped are compared to the cancerous cell.

  • Low-grade cancers, or well-differentiated cancers, resemble normal bladder cells.
  • High-grade cancers are poorly differentiated or undifferentiated cancers, doesn't resemble normal bladder cells and are likely to become invasive and spread to other body parts and may recur.

Treatment of Bladder Cancer by Stages

Non invasive and Non-muscle-invasive bladder cancer- Stage 0a, 0is, I

Patients with low-grade non-invasive cancer (Stage 0a) are treated firstly with TURBT. Low-grade non-invasive cancer seldom turns into aggressive or metastatic cancer, but patients can have a chance to develop other low-grade cancer in the course of their life. To lower the risk of recurrence, patients may receive intravesical chemotherapy after TURBT.

  • People with high-grade non-invasive (stage Ta), carcinoma in situ (Tis), or non-muscle invasive(stage T1) bladder cancer are most commonly treated with TURBT, followed by local intravesical Bacillus Calmette-Guerin. This combined treatment narrows the risk of cancer recurrence or developing muscle-invasive cancer ?1?. Before going for BCG, patients need another TURBT to check that the cancer has not spread to muscles.

The first round of BCG is given for six weeks, once every week. The provider performs cystoscopy or bladder biopsy to check if cancer cells are eliminated. If cancer is gone, patients receive maintenance therapy with BCG, which is given once every three months for the first six months and then once every six months for 1 to 3 years. It will then be followed by long-term surveillance.

  • People with high-grade, non-muscle-invasive bladder cancer

People with this type of bladder cancer are at higher risk of cancer recurrence, and the tumor may return at an advanced stage with a chance of developing metastatic bladder tumour. To prevent this from happening, the urologist may recommend removing the whole Bladder, called a radical cystectomy, mainly if the person is young and has a large or several tumors during diagnosis or other aggressive features.

  • People with high-risk, non-muscle-invasive bladder cancer

Patients may also be treated with pembrolizumab, an immune checkpoint inhibitor that targets the PD-1 protein. The FDA approves Pembrolizumab for bladder cancer treatment that has not responded to, BCG treatment (known as "BCG-unresponsive") and radical cystectomy cannot be done for other medical reasons, or the patient chooses not to have that surgery.

Also Read:Treatments Approaches for Cancer

Bladder preservation

An approach that uses chemotherapy and radiation therapy after optimal TURBT may provide the same effects as removing the Bladder and is called trimodal therapy or the bladder preservation approach ?4?.

The type of chemotherapy used for patients undergoing bladder radiation therapy can comprise:

  • gemcitabine alone
  • cisplatin alone
  • a combination of mitomycin-C (available as a generic drug) and fluorouracil (5-FU).

Metastatic urothelial cancer-Stage IV

If cancer in the Bladder has spread to other parts of the body, that is, metastasized, combined treatment may be used to control and manage cancer ?5?. Clinical trials can be a good option you should consider.

  • Chemotherapy: Presently, The first-line treatment option includes chemotherapy regimens that have cisplatin or carboplatin. These regimens include MVAC (rarely), dose-dense MVAC, and gemcitabine-cisplatin. Carboplatin regimens, such as gemcitabine, can be used to treat people with metastatic urothelial cancer who can't receive cisplatin for whatever reasons. Chemotherapy with docetaxel or paclitaxel, or pemetrexed are alternatives for later-line treatment.
  • Immunotherapy: Immune checkpoint inhibitors approved by the FDA to treat people with metastatic cancer whose tumor is not shrunk or balanced by platinum-based chemotherapy. The only immunotherapy shown to help people live longer in this phase 3 clinical trial setting is pembrolizumab.
  • Targeted therapy: FDA approved erdafitinib to treat people with locally advanced or metastatic urothelial carcinoma after platinum chemotherapy did not stop cancer. Erdafitinib is a targeted therapy pointing at the DNA changes in theFGFR2orFGFR3genes. Patients must have their tumors tested for these changes to receive the treatment. The FDA also approved enfortumab vedotin-ejfv (Padcev) to treat locally advanced or metastatic urothelial carcinoma in people who have also received a PD-1 or PD-L1 immune checkpoint inhibitor and platinum chemotherapy and for those who can't receive cisplatin chemotherapy and have already received one or more Treatments by Stages of Bladder Cancer.

References

  1. 1.
    Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: Epidemiology, staging and grading, and diagnosis. Urology. Published online December 2005:4-34. doi:10.1016/j.urology.2005.07.062
  2. 2.
    Babjuk M, Burger M, Zigeuner R, et al. EAU Guidelines on NonMuscle-invasive Urothelial Carcinoma of the Bladder: Update 2013. European Urology. Published online October 2013:639-653. doi:10.1016/j.eururo.2013.06.003
  3. 3.
    Magers MJ, Lopez-Beltran A, Montironi R, Williamson SR, Kaimakliotis HZ, Cheng L. Staging of bladder cancer. Histopathology. Published online December 18, 2018:112-134. doi:10.1111/his.13734
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