Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder.

This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with urothelial cell carcinoma of the urinary bladder. It is categorized according to the stage of the disease using the tumor node metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.

INTRODUCTION

According to the cancer incidence report in Saudi Arabia for the year 2010, there were 243 new cases of urinary bladder cancer accounting for 2.4% of all newly diagnosed cases of cancer. It ranked the 8th and 20th most common cancer in males and females, respectively. It affected 193 (78.4%) males and 50 (20.6%) females with a male to female ratio of 385:100. The overall age-standardized incidence rate was 2.3/100,000, in males it was 3.6/100,000 and in females it was 1/100,000. The median age at diagnosis was 63 among males (range 11–101 years) and 64 among females (range 28–97 years).[1]

STAGING

The staging is shown in Appendix 1.[2]

GRADING

The World Health Organization grading of urinary tumors 2004[3] will be used as follow:

Urothelial papilloma

Papillary urothelial neoplasm of low malignant potential

Low-grade papillary urothelial carcinoma

High-grade papillary urothelial carcinoma.

PATHOLOGY REPORTING OF BLADDER TUMOR SPECIMEN MUST AT LEAST INCLUDE THE FOLLOWING INFORMATION

The histological tumor type

The presence or absence of lamina propria and muscularis propria

The depth of invasion, i.e., pathological T-stage referred to in section 1

The presence or absence of carcinoma in situ (CIS)

The grade of tumor as referred to in section 2

Any urothelial carcinoma a variant.[4]

EVALUATION OF BLADDER TUMOR

Evaluation should include history and physical examination, urine cytology, and diagnostic cystoscopy

If the findings of the diagnostic cystoscopy are suggestive of noninvasive

Transurethral resection of bladder tumor (TURBT)

Single-dose intravesical chemotherapy (mitomycin or doxorubicin) should be considered within 24 h from TURBT to reduce the rate of local recurrence[5]

Imaging of the upper tract (ultrasound, computed tomography [CT], or magnetic resonance imaging [MRI] urogram) if not already done.

If the findings of the diagnostic cystoscopy are suggestive of invasive, or high-grade disease

Consider imaging (CT scan or MRI) of the abdomen and pelvis before TURBT (EL3)[67]

Examination under anesthesia and TURBT.

MANAGEMENT OF NONMUSCLE INVASIVE UROTHELIAL BLADDER CARCINOMA

Repeat TURBT within 2–4 weeks is indicated if incomplete resection, high-grade, pathological T1, or there is no muscle in specimen.[8910]

Risk stratification for nonmuscle invasive urothelial bladder carcinoma

This depends on the following factors: Tumor stage, grade, presence of CIS, number of tumors, tumor size, and prior recurrence rate:[11]

Low-risk nonmuscle invasive bladder cancer (NMIBC) (solitary small volume, low-grade Ta)

Intermediate risk NMIBC (multifocal and/or large volume low-grade Ta, recurrence at 3 months)

High-risk NMIBC (high-grade Ta, all T1, CIS).

Low-risk

Surveillance cystoscopy (3–6 months) intervals [Appendix 2].

Intermediate-risk

Adjuvant intravesical (6-week induction) bacillus Calmette–Guerin (BCG) (preferred) or mitomycin[12]

Surveillance cystoscopy and cytology (3–6 months) intervals

Upper tract imaging every 2 years or as indicated.

High-risk including carcinoma in situ

Adjuvant intravesical BCG [6-week induction followed by maintenance see Appendix 3][1314]

Close surveillance cystoscopy, cytology, and upper tract imaging

Consider early cystectomy in selected patients.[15]

Recurrence of nonmuscle invasive disease

TURBT

Adjuvant intravesical therapy if not given before or as a second induction[16]

If two induction of adjuvant intravesical therapy was given before, then consider changing the intravesical therapy

Consider early cystectomy in recurrent CIS, T1, and high-grade disease with prior treatment with no more than two induction of intravesical therapy.[1718]

Positive urine cytology without gross evidence of disease

Multiple biopsies of the bladder and prostatic urethra[192021]

Selective cytology of the upper tract

Upper tract imaging (CT or MRI urogram, or retrograde pyelogram)

Ureteroscopy if suspicion of upper tract tumor.

MANAGEMENT OF MUSCLE INVASIVE UROTHELIAL BLADDER CARCINOMA

Staging should include complete blood count, renal function and serum electrolytes, liver function test including alkaline phosphatase, imaging of the chest, abdomen, and pelvis

(CT or MRI), bone scan if elevated alkaline phosphatase or symptoms of bone pain.[22]

Clinical T2–T4a disease with negative lymph nodes

Neoadjuvant cisplatin-based combination chemotherapy[232425]

Considered in clinical T2

Strongly recommended in clinical T3.

Radical cystectomy with extended lymphadenectomy (open, laparoscopic, or Robotic) is considered the standard treatment[26]

Bilateral pelvic lymphadenectomy should be performed and include at a minimum common, internal and external iliac, and obturator nodes

Bladder preservation with tri-modality combination of maximum TURBT followed concurrent chemoradiation with early radical cystectomy in failure is an alternative to upfront radical cystectomy[262728293031] in selected patients with solitary disease, no CIS, no hydronephrosis, normal renal function, and adequate bladder capacity[32]

In patient undergoing bladder preservation, early evaluation is recommended after 45 Gy, if there is residual/recurrent tumor than consider cystectomy and if there is the complete response then complete radiotherapy to 60–65 Gy total dose[33]

Patients who are not candidate for radical treatment, consider TURBT and/or palliative radiotherapy

After surgery with positive lymph nodes or pathological T3 or T4 disease, consider adjuvant cisplatin-based combination chemotherapy if no neoadjuvant was given.[34]

Clinical T4b or positive locoregional lymph node disease

Cisplatin-based combination chemotherapy or chemoradiation

Reevaluate the response during the treatment with imaging and/or TURBT

If chemoradiation was used:

Observation for patients who achieved complete response

If partial response consider cystectomy.

If cisplatin-based combination chemotherapy was used:

In responding patients, consider cystectomy or chemoradiation

In nonresponding patients, consider chemoradiation.

Metastatic disease

Chemotherapy is the mainstay of treatment

Patients with normal renal function and fit for chemotherapy (PS 0–2) are treated with combination cisplatin and gemcitabine for a maximum of 6 cycles[35]

Patients with decreased renal function and/or unfit (PS 3) are treated with combination of Carboplatin and gemcitabine or single agent gemcitabine or carboplatin[36]

Patient who relapse or progress on the above regimens may be given vinflunine or taxanes as second-line chemotherapy

Patients who present with local recurrence may benefit from palliative radiation therapy

Consider clinical trials.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.