74 y/o woman with history of bladder cancer, diagnosed in May 2009 – admitted now for partial cystectomy.
The diagnosis of bladder cancer was made when she first presented with painless gross hematuria, cystoscopy revealed a large lesion indwelling the dome of the bladder. She underwent Trans Urethral Resection of the Bladder Tumor ( TURBT). Pathology at that time revealed a poorly differentiated (grade 3) carcinoma which was confirmed as primary urothelial carcinoma by immunohistochemistry ( T1NxMx).
The patient subsequently presented to the ER two weeks after TURBT with significant hematuria, required cystoscopy and fulguration of the biopsy site. Biopsies obtained this time involved only scar tissue that did not show malignancy ( no bladder tissue was included in the biopsy material – uncertain complete resection).
A decision was made to proceed with elective partial cystectomy for which the patient was admitted in 8/2009.
No new episodes of hematuria. No dysuria or urgency. No weightloss/ bone pain
85 y/o woman who was diagnosed with carcinoma in-situ ( Tis, Grade 3, right lateral bladder wall) in August 2008, treated with a course of Intra-vesical BCG, was then enrolled in to cystoscopic surveillance with biopsies. Seven months after initial diagnosis (3/09), the patient was found to have high grade papillary urothelial carcinoma ( Ta, G3) at a different site ( left bladder neck).
73 y/o man who was diagnosed with carcinoma in-situ ( Tis, Grade 3) in April 2004, treated with a course of Intra-vesical BCG, was then enrolled in to cystoscopic surveillance with biopsies. One year after initial diagnosis (4/2005), the patient was found to have high grade muscle invasive urothelial carcinoma ( T2, G3).
88 y/o man with hx of Renal Cell Carcinoma s/p Right Nephrectomy (2003), developed hematuria in mid-2008 and cystoscopy revealed bladder tumor, subsequent TURBT (8/08) demonstrated Muscle invasive high grade urothelial carcinoma ( G3, T2), treated with Radical cystectomy which is the standard of care for T2 lesions, however, was on frozen section, was found to have metastatic lymphadenopathy ( T2N1M0 – Stage IV TCC). The patient was started on palliative chemotherapy with Gemcitabine.
Alkaline phosphatase was elevated at 174 but bone scan revealed Paget’s disease with out any bony metastases ( 4/2009).
Repeat CT scan in 4/2009 revealed increasing retroperitoneal lymphadenopathy. Chemotherapy was continued.
Restaging CT scan performed in 8/2009 revealed sclerotic bony lesions in the lumbar vertebrae and osteolytic lesion in right acetabulum, pulmonary nodules, Right groin and para-aortic lymphadenopathy indicating a diffuse metastatic disease recommended orthopedic stabilization of the hip / hip replacement patient refused and hence given Zolendronic acid + palliative RT. Possible palliativer chemotherapy to be started as well.
Bladder Cancer Polychronotropic Recurring in time and space any where along the urothelial tract ( from renal pelvis to proximal two-thirds of urethra)
Stage grouping Stage 0a Ta N0 M0 Stage 0is Tis N0 M0 Stage I T1 N0 M0 Stage II T2a N0 M0 T2b N0 M0 Stage III T3a N0 M0 T3b N0 M0 T4a N0 M0 Stage IV T4b N0 M0 Any T N1 M0 Any T N2 M0 Any T N3 M0 Any T Any N M1
In addition to tumor stage (Tis, Ta, or T1), histologic grade also influences
rate of recurrence
Grade I : Well differentiated
Grade II : Moderately differentiated
Grade III : Poorly differentiated
In one study, grade was the most significant tumor variable in superficial bladder cancer predicting for the development of invasive carcinoma. ( Superficial bladder cancer: the primacy of grade in the development of invasive disease. AU Torti FM; Lum BL; Aston D; MacKenzie N; Faysel M; Shortliffe LD; Freiha F SO J Clin Oncol 1987 Jan;5(1):125-30)
Patients with multiple papillary tumors at the time of presentation have higher rates of recurrence of both non-muscle invasive and invasive cancer.
May provide an additional way to identify non-muscle invasive bladder cancers that are likely to progress to muscle invasive or high-grade disease eg: abnormalities in p53 may be associated with a less favorable prognosis where as, the presence of mutations in fibroblast growth factor receptor 3 (FGFR3) may indicate favorable prognosis
Gold standard was MVAC (methotrexate, vinblastine, adriamycin, cisplatin) but very toxic - needs good PS and renal function, best for nodal disease only.
Gemcitabine/cisplatin is as good as MVAC with less neutropenia and mucositis and is the first line therapy.
In patients with GFR < 60ml/min, carboplatin must be substituted for cisplatin in the above regimens
Newer drugs - Taxol, gemcitabine – combinations of these agents with lower toxicity profile can be used based on patient’s performance status, other comorbidities ( neuropathy etc), compromised liver or kidney function .