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Low Grade Bladder Cancer Recurrence

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Fluorescence In Situ Hybridization

Prognostic factors for T1 high grade bladder cancer recurrence and estimation of overall survival be

Detection of specific DNA alterations known to be associated with bladder cancer is possible using multitarget FISH. DNA probes hybridize with abnormal chromosomal sites and may be visualized using fluorescence microscopy. According to several published articles, FISH has significantly greater sensitivity than conventional cytology while maintaining the known high specificity of cytology.

The DNA probes chosen for available FISH testing are based on the highest-yielding combination of chromosomal abnormalities. Three of these are centromeric enumeration probes, which allow rapid determination of aneuploidy of chromosomes 3, 7, and 17, the most commonly related to bladder cancer. The fourth probe is used to label the 9p21 locus, known to be the site of a significant tumor suppressor gene. Loss of this tumor suppressor gene is also related to cancer recurrence and progression. A positive result is defined as a gain of 2 or more chromosomes in 4 cells, isolated loss of 9p21 in 12 cells, or isolated gains of only 1 chromosome in 10% or more cells. Most FISH-positive patients develop recurrent urothelial carcinoma within 1 year.

Among patients with bladder cancer in whom cytology results were negative, atypical, and suggestive, FISH detected 60%, 89%, and 100%, respectively, allowing identification of cancer in most patients in whom cytology failed to detect cancer recurrence.

Bcg Relapse And Salvage Regimens

Guideline Statement 22

22. In an intermediate- or high-risk patient with persistent or recurrent disease or positive cytology following intravesical therapy, a clinician should consider performing prostatic urethral biopsy and an upper tract evaluation prior to administration of additional intravesical therapy.


Urothelial carcinoma, particularly CIS, is considered a field-change disease with the entire urothelium at risk in affected individuals. Clinicians should remain aware of sites outside the bladder as potential sources for metachronous tumors. While the initial diagnostic evaluation includes radiographic/endoscopic visualization of the entire urinary tract, the extra-vesical urothelium remains at long-term risk for subsequent tumor development. Moreover, these sites may harbor disease and contribute to cancer recurrence within the bladder.

Of note, the Panel recognizes that evaluation of the upper urinary tract and urethra may be withheld in select patients who have received a single induction course of intravesical BCG and subsequently have persistent evidence of disease and are to undergo a second course of BCG.

Guideline Statement 23

23. In an intermediate- or high-risk patient with persistent or recurrent Ta or CIS disease after a single course of induction intravesical BCG, a clinician should offer a second course of BCG.


Guideline Statement 24


Guideline Statement 25


Guideline Statement 26

Bladder Cancer And Treatment Options For Recurrence

If your bladder cancer recurs, you will undergo tests to find out more about the cancer cells.1-3 The type of treatment will depend on where the cancer cells have recurred and what type of treatments you received before. After learning more about the recurrence, your cancer care team will discuss all the possible treatment options that are available for you.

Some treatment options that can be used for bladder cancer recurrence, either alone or in combination, include:

  • Surgery

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Ajcc Stage Groupings And Tnm Definitions

The American Joint Committee on Cancer has designated staging by TNM classification to define bladder cancer.

Table 1. Definitions of TNM Stages 0 and 0isa

Poorly differentiated.
  • Cowan NC, Crew JP: Imaging bladder cancer. Curr Opin Urol 20 : 409-13, 2010.
  • Green DA, Durand M, Gumpeni N, et al.: Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques. BJU Int 110 : 1463-70, 2012.
  • Bochner BH, Hansel DE, Efstathiou JA, et al.: Urinary Bladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer 2017, pp 757-65.
  • How Long Will You Live If You Have Bladder Cancer

    Expression of Her2 and TP53 in low grade and high bladder ...

    The survival rate depends on the stage of cancer at diagnosis and other health issues.

    Overall, 70 to 90 percent of people with localized bladder cancer will live for at least five years or more. The physician calculates this with the help of survival rates. Survival rates indicate the percentage of people who live with a certain type of cancer for a specific time. The physician often uses an overall five-year survival rate. Factors that may affect survival rate include

    Table. Five-year survival rates of different stages of bladder cancer

    Bladder cancer SEER stages Five-year relative survival rate
    In situ alone 96
    All SEER stages combined 77

    The surveillance, epidemiology, and end results stages are taken from the SEER database, maintained by the National Cancer Institute. SEER database groups cancers into localized, regional, and distant stages.

    • Localized: There is no indication that cancer has spread outside the bladder.
    • Regional: Cancer has invaded the nearby structures or lymph nodes.
    • Distant: Cancer has spread to distant parts of the body, such as the lungs, liver, or bones.

    Thus, bladder cancer, if detected in the early stage is treatable and has higher survival rates. However, if the cancer is detected in the advanced stages, treatment becomes difficult and the survival rate is low.

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    Carcinogenesis And Risk Factors

    Increasing age is the most important risk factor for most cancers. Other risk factors for bladder cancer include the following:

    • Use of tobacco, especially cigarettes.
    • Family history of bladder cancer.
    • HRAS mutation .
    • Rb1 mutation.
  • Occupational exposure to chemicals in processed paint, dye, metal, and petroleum products that include:
  • Aluminum production .
  • Aminobiphenyl and its metabolites.
  • Aromatic amines, benzidine and its derivatives.
  • Treatment with cyclophosphamide, ifosfamide, or pelvic radiation for other malignancies.
  • Use of Chinese herbs: aristolochic acid extracted from species of Aristolochia fangchi.
  • Exposure to arsenic.
  • Arsenic in well water.
  • Inorganic arsenic compounds .
  • Exposure to chlorinated aliphatic hydrocarbons and chlorination by-products in treated water.
  • Schistosoma haematobium bladder infections .
  • Neurogenic bladder and associated use of indwelling catheters.
  • There is strong evidence linking exposure to carcinogens to bladder cancer. The most common risk factor for bladder cancer in the United States is cigarette smoking. It is estimated that up to half of all bladder cancers are caused by cigarette smoking and that smoking increases a persons risk of bladder cancer two to four times above baseline risk. Smokers with less functional polymorphisms of N-acetyltransferase-2 have a higher risk of bladder cancer than other smokers, presumably because of their reduced ability to detoxify carcinogens.

    Stage Iv Bladder Cancer Treatment

    Only a small fraction of patients with stage IV bladder cancer can be cured, and for many patients, the emphasis is on palliation of symptoms. The potential for cure is restricted to patients with stage IV disease with involvement of pelvic organs by direct extension or metastases to regional lymph nodes.

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    Selecting And Testing Gemcitabine

    When Dr. Messing began research on gemcitabine as a possible way to reduce recurrences more than a decade ago, the drug was not widely used for bladder cancer. “We tried to pick an agent that we thought would be safe and effective,” he said.

    The researchers decided to compare gemcitabine against placebo rather than mitomycin C, based on studies showing how infrequently patients received some form of chemotherapy following surgery despite guidelines recommending this approach.

    “If the new procedure were adopted widely, we could spare patients a lot of suffering from repeated surgeries and save health care costs associated with those surgeries,” Dr. Messing said.

    “Now that we have the results of the trial,” he went on, “we hope that patients and physicians will embrace this approach to treatment.”

    Can I Lower My Risk Of Cancer Returning

    Controversies in Non Muscle Invasive Bladder Cancer

    Unfortunately, researchers do not yet understand exactly what causes bladder cancer to recur in some people, but not in others.2 There are studies being carried out to try and find out if there are any vitamins, minerals, supplements, or medicines that might help to reduce the risk of recurrence. But as of now, there is no proof that any of these things have an effect on the chance that bladder cancer will recur.

    Maintaining a healthy body and lifestyle is good for your overall health, however. Following a healthy diet, staying active, and avoiding unhealthy behaviors, such as smoking, is a good idea for everyone. If you find yourself worrying about bladder cancer recurrence, stress-relieving activities such as exercise or meditation might help to reduce your anxiety.

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    Treatment Options For Recurrent Bladder Cancer

    Treatment options for patients with recurrent bladder cancer include the following:

    Palliative radiation therapy should be considered for patients with symptomatic tumors.

    Clinical trials

    Recurrent or progressive disease in distant sites or after definitive local therapy has an extremely poor prognosis, and clinical trials should be considered whenever possible.

    Late Recurrence Beyond 5

    We next focused on patients who were tumor-free for more than 5 years from initial TUR-BT to first tumor recurrence and WP, called late recurrence and late WP. We identified 76 patients in this category, among whom adjuvant IVI had been performed in 40 patients . The mean age of the patients was 61.1 years , and solitary/multiple tumors were seen in 53/23 patients, respectively. Eleven patients experienced late recurrence, and of them, 5 patients had late WP . There were no significant differences in age, gender, multiplicity, smoking status or adjuvant IVI performed in patients with or without late recurrence, and there were no significant risk factors of late recurrence. The average time to late recurrence and late WP was 103.5 and 104.5 months, respectively. Nine of 11 patients whose cancer recurred in years 5 and 10 in our study were diagnosed at a follow-up cystoscopy. Meanwhile, recurrence in 2 patients who were tumor-free beyond 10 years was found by gross hematuria. WP to high grade Ta, low grade T1, Tis, UTR, and high grade T3 were observed in one case in each. Also, 4 patients experienced WP on the first late recurrence while only one patient did on the 2nd recurrence.

    Table 3 Clinical characteristics of 76 patients with a tumor-free period for more than 5 years from initial diagnosis

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    Standard Treatment Options For Stages Ii And Iii Bladder Cancer

  • Transurethral resection with fulguration .
  • The most common treatments for muscle-invasive bladder cancer are radical cystectomy and radiation therapy. There is no strong evidence from randomized controlled trials to determine whether surgery or radiation therapy is more effective. There is strong evidence that both therapies become more effective when combined with chemotherapy. The treatments with the highest level of evidence supporting their effectiveness are radical cystectomy preceded by multiagent cisplatin-based chemotherapy and radiation therapy with concomitant chemotherapy.

    Radical cystectomy

    Radical cystectomy is a standard treatment option for stage II and stage III bladder cancer, and its effectiveness at prolonging survival increases if it is preceded by cisplatin-based multiagent chemotherapy. Radical cystectomy is accompanied by pelvic lymph node dissection and includes removal of the bladder, perivesical tissues, prostate, and seminal vesicles in men and removal of the uterus, fallopian tubes, ovaries, anterior vaginal wall, and urethra in women. Studies of outcomes after radical cystectomy report increased survival in patients who had more, rather than fewer, lymph nodes resected whether this represents a therapeutic benefit of resecting additional nodes or stage migration is unknown. There are no randomized controlled trials evaluating the therapeutic benefit of lymph node dissection in this setting.

    Evidence :

    Evidence :

    Segmental cystectomy

    Study: Gemcitabine Helps Prevent Recurrence Of Low

    Recurrent Ta Low

    Published On: May 16, 2018Shared by Rosanne Fohn

    A multi-institution clinical trial involving researchers from UT Health San Antonio shows significantly lower recurrence of bladder cancer in patients who received the chemotherapy drug gemcitabine.

    The results of the trial were published May 8, 2018, in the Journal of the American Medical Association. Robert Svatek, M.D., a UT Health San Antonio genitourinary oncologist, was the universitys study leader.

    Dr. Svatek was not only involved with conducting this study, but he and his site , along with our site , were the two leading recruiting sites for patients, said Edward M. Messing, M.D., the national leader of the study.

    In addition to his oncology practice, Dr. Svatek is an associate professor in the Department of Urology and chief of the Division of Urologic Oncology at UT Health San Antonio.

    In the trial, 406 patients with newly diagnosed bladder cancer or low-grade bladder cancer that had not invaded the muscle wall were randomly assigned to one of two groups. One group received one treatment of gemcitabine and a saline solution and the other group received one treatment of only saline solution, both directly instilled into the bladder through a catheter within three hours following surgery. Gemcitabine is already approved by the U.S. Food and Drug Administration to treat several types of cancer.

    The trial was supported by the National Cancer Institute as well as Eli Lilly and Company.

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    Treating Stage I Bladder Cancer

    Stage I bladder cancers have grown into the connective tissue layer of the bladder wall , but have not reached the muscle layer.

    Transurethral resection with fulguration is usually the first treatment for these cancers. But it’s done to help determine the extent of the cancer rather than to try to cure it. If no other treatment is given, many people will later get a new bladder cancer, which often will be more advanced. This is more likely to happen if the first cancer is high-grade .

    Even if the cancer is found to be low grade , a second TURBT is often recommended several weeks later. If the doctor then feels that all of the cancer has been removed, intravesical BCG or intravesical chemo is usually given. If all of the cancer wasn’t removed, options are intravesical BCG or cystectomy .

    If the cancer is high grade, if many tumors are present, or if the tumor is very large when it’s first found, radical cystectomy may be recommended.

    For people who arent healthy enough for a cystectomy, radiation therapy might be an option, but the chances for cure are not as good.

    Tumor Recurrence And Worsening Progression Rate In Entire Patient Population

    The mean age of the patients was 62.9 years and the median follow-up interval was 101.5 months . Solitary/multiple tumors were seen in 114/76 patients, respectively. Tumor recurrence occurred in 82 patients . Most patients who had tumor recurrence could be diagnosed by the routine follow-up cystoscopic examination except for 3 patients who were detected due to gross hematuria. When we divided the patients into two groups, those with or without tumor recurrence, there were no significant differences in age, gender, IVI or smoking status between the two groups . The recurrence rate in multiple tumors was significantly higher than that in solitary tumors . Univariate and multivariate analyses demonstrated that multiple tumor and absence of IVI were significant risk factors for tumor recurrence . Kaplan-Meier curves demonstrated that the 5-year recurrence free survival rate for solitary tumors was significantly higher than that for multiple tumors , and also higher for patients receiving intravesical instillation .

    Table 1 Clinical characteristics of all 190 patientsFigure 2

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    Adherence And Cost Of Surveillance

    Only 40% of patients adhere to the recommended schedule of bladder cancer surveillance. A survey of 498 in nine European countries found that while 80% purported to follow EAU guidelines, patients with low-risk non-muscle-invasive bladder cancer were likely to be overmonitored while those with high-risk diasese were undermonitored.

    Failure to undergo standard surveillance has been attributed to numerous issues. Advanced age and lower-risk tumors are associated with a failure to follow guidelines, as are lower economic status and urban dwelling.

    Although the incidence of bladder cancer is less than that of prostate cancer, expenditures are almost twice as high for bladder cancer because of its chronic nature and the need for long-term surveillance. According to the US Agency for Health Research and Quality, annual expenditures are $2.2 billion for bladder cancer versus $1.4 billion for prostate cancer. This suggests a close assessment of surveillance techniques and standards is appropriate.

    Turbt/ Repeat Resection: Timing Technique Goal Indication

    Diagnosis & Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guidelines

    Guideline Statement 12

    12. In a patient with non-muscle invasive disease who underwent an incomplete initial resection , a clinician should perform repeat transurethral resection or endoscopic treatment of all remaining tumor if technically feasible.


    Incomplete resection is likely a significant contributing factor to what have been described and diagnosed as early recurrences, as tumors have been noted at the first follow-up cystoscopic evaluation in up to 45% of patients. 57 The Panel recognizes specific, albeit rare, circumstances in which transurethral resection is not likely to impact clinical management and may be omitted for patients with incompletely resected non-muscle invasive disease. Examples of such patients include those with large-volume, high-grade tumors not amenable to complete endoscopic resection for whom immediate radical cystectomy is planned. An additional example includes those patients with a tumor diagnosed within a bladder diverticulum and for whom subsequent surgical resection is planned. However, for the majority of patients, complete resection is essential for adequate staging and optimal clinical management. Although surgeons may utilize BLC for this situation, of note, there is insufficient evidence in this repeat transurethral resection setting to support the routine use of enhanced or BLC versus standard WLC, particularly in light of the noted increase in false positive diagnosis with BLC following recent TURBT. 116-118


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    Treating Stage Iii Bladder Cancer

    These cancers have reached the outside of the bladder and might have grown into nearby tissues or organs and/or lymph nodes . They have not spread to distant parts of the body.

    Transurethral resection is often done first to find out how far the cancer has grown into the bladder wall. Chemotherapy followed by radical cystectomy is then the standard treatment.Partial cystectomy is rarely an option for stage III cancers.

    Chemotherapy before surgery can shrink the tumor, which may make surgery easier. Chemo can also kill any cancer cells that could already have spread to other areas of the body and help people live longer. It can be especially useful for T4 tumors, which have spread outside the bladder. When chemo is given first, surgery to remove the bladder is delayed. The delay is not a problem if the chemo shrinks the cancer, but it can be harmful if it continues to grow during chemo. Sometimes the chemo shrinks the tumor enough that intravesical therapy or chemo with radiation is possible instead of surgery.

    Some patients get chemo after surgery to kill any cancer cells left after surgery that are too small to see. Chemo given after cystectomy may help patients stay cancer-free longer, but so far its not clear if it helps them live longer. If cancer is found in nearby lymph nodes, radiation may be needed after surgery. Another option is chemo, but only if it wasn’t given before surgery.

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