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Non-invasive papillary urothelial G2 carcinoma

Short summary

65-year-old male was recently diagnosed with a bladder tumor. He had abdominal imaging which revealed a space occupying lesion involving the left bladder wall as well as a mild degree of left hydronephrosis. During his operation a papillary tumor was resected and a stent was inserted into the left ureter. Pathology revealed Transitional cell carcinoma of the bladder non invasive (Ta) G2.

Patient's questions

1. As regards the diagnosis based on the histology test results, are there more effective therapies for this type of neoplasia?
2. Are there any other tests that the patient should have?

Medical Background

The patient, male, 65, has arterial hypertension and ischemic cardiopathy and is being treated with carvedilol and acetylsalicylic acid with good results.

Following non specific symptoms, the patient had an echotomography of his upper and lower abdomen which showed a “widespread hetero-productive formation involving the left paramedian bladder floor. Concomitant initial hydronephrosis in left kidney. Small cystic formation at inferior pole of right kidney with a maximum diameter of 1.5 cm.” The other organs investigated were within normal limits.
Subsequently, the patient had a urography that confirmed an infiltrating neoformation of left lateral wall of the bladder and ureteral outlet which had a filiform appearance (due to infiltration?). No other significant findings in kidneys, upper urinary excretory passages and right ureter.
A cytology test of urinary sediment showed the presence of urothelial aggregates probably exfoliated due to low-grade transitional papillary neoplasia, which were virtually undistinguishable from non-neoplastic conditions (calculosis, bladder hypertrophy, recent catheterization).
Chest x-ray: within normal limits.
Blood chemistry tests were within normal limits.
HIV and hepatitis screening were negative.
---: Hospitalization during which the patient’s neoplasia was resected endoscopically, the results of which were as follows: “…on bladder side of posterior contour of ureteral neck and left hemitrigone and partially on left lateral wall, a vast papillary neoformation type b which was resected separating the implantation base. The left ostium affected by the neoformation was also resected and sent for cytology tests. A left ureteral catheterization was then put in place for reconstruction purposes.” Three samples were sent for histology tests: 1) Bladder neoformation biopsy: Non-invasive papillary urothelial G2 carcinoma (Ta). 2) Implantation base: Subepithelial connective tissue and muscular coat not affected by neoplasia. 3) Left ureteral ostium biopsy: Fragment with no lesions.
The patient was discharged and prescribed a cycle of topical treatment with MITOMYCIN C.


Medical opinion

Bladder cancer is the fifth most common cancer in men and accounts for slightly more than 12,000 cancer-related deaths per year in the United States. Approximately 70% of bladder tumors present as superficial lesions. Tumor grade and stage clearly have an influence on tumor recurrence and progression. Low-grade Ta lesions recur at a rate of 50% to 70% and have approximately a 5% chance of progression.2-3% of the patients with TCC of the bladder will develop similar disease in the kidneys or ureters.

The goal of intravesical therapy with chemotherapeutic agents is to decrease recurrence, prevent progression, and eradicate residual disease after TUR resection. Mitomycin C is a cross-linking agent that, in part, inhibits DNA synthesis. It is usually instilled weekly for 6 to 8 weeks at dose ranging from 20 to 60 mg. As a result of this treatment there is a decrease in recurrence ranging from 19% to 42% .There is no significant effect of Mitomycin C over TUR alone on decreasing tumor progression over 5 years. It was shown that a single immediate instillation delivered within 6 hours of TUR decreased recurrence rates by approximately 50% and increased the recurrence-free interval. The significant side effects of Mitomycin C include chemical cystitis, which can occur in up to 40% of patients, as well as decreased bladder capacity, palmar desquamation, and skin rash. Skin contact should be avoided. Other effects, such as leukopenia and bladder contraction (0.05%), are rare.
In view of these data Mitomycin C bladder instillations is the treatment of choice for this patient.
My recommendations regarding this treatment are as follows:
1)    6 weekly instillation of Mitomycin C 40 mg followed by a cystoscopy performed at a two to three weeks interval from the last treatment. The ureteral stent placed during surgery should be removed during this cytoscopy.
2)    Routine follow-up cystoscopies and urine cytology every three months during the first three years, every six months during the next two years and a yearly check up thereafter.
3)    Imaging of the kidneys and ureters should be done once a year to rule out TCC in the upper tract.
If the patient should develop an allergic reaction to Mitomycin C, I recommend switching to BCG instillation. Smoking cessation is mandatory in these patients and he should be consulted to do so.