Recommendations

Strength of the recommendation

DIAGNOSIS AND PATHOLOGY/MOLECULAR BIOLOGY

Hematuria is the most common presenting symptom in bladder cancer and should in all cases be investigated

Strong

The diagnosis of bladder cancer is based on cystoscopic examination of the bladder and histological evaluation of tissue obtained either with cold-cup biopsy or TURBT, where complete resection of all tumor tissue should be achieved whenever possible and muscle tissue should be included in the biopsies, except when a Ta/LG is expected

Strong

Cross-sectional upper tract imaging (CT/MRI urography) is recommended to screen for synchronous UTUC, in cases of HG bladder cancer

Conditional

Pathological diagnosis should be made according to latest WHO classification

Strong

In addition to stage and grade, presence and percentage of variant histology, lymphovascular invasion and presence of muscularis propria should be reported

Strong

Urine cytology can facilitate the diagnosis of HG UC but cannot be used as the primary method of histological diagnosis

Conditional

STAGING AND RISK ASSESSMENT

Staging of NMIBC

Patients with NMIBC should be classified into four risk categories based on tumor characteristics (low , intermediate , high  and very-high-risk) as shown in table 1.

Strong

Regional and distant staging of MIBC

In patients with invasive disease (>T1), regional and distant staging should be carried out with further imaging studies such as contrast-enhanced CT of chest-abdomen-pelvis or MRI of abdomen/pelvis combined with chest CT

Strong

FDG-PET-CT may aid in the detection of LN and distant metastases, and in cases with impaired renal function.

Conditional

MANAGEMENT OF LOCAL/LOCOREGIONAL DISEASE

Treatment of NMIBC

In patients with low-risk NMIBC and those with small papillary recurrences, detected >1 year after the previous tumor, single, immediate, intravesical chemotherapy instillation, such as mitomycin C, or gemcitabine is recommended, in combination with continued cystoscopic surveillance

Strong

In patients with intermediate-risk NMIBC, additional courses of intravesical therapy are recommended, and is consisting of either instillations of Chemotherapy for a maximum of 1 year, or 12 months of BCG instillation therapy with six BCG instillations at weekly intervals, followed by three BCG instillations each at 3, 6 and 12 months

Strong

In patients with high-risk NMIBC, full dose intravesical BCG for 1-3 years (at least 1 year) is recommended with induction as previously mentioned for 6 weeks followed by instillations at 3, 6, 12, 18, 24, 30 and 36 months

Strong

Planned cystoscopic surveillance per high risk NMIBC schedule should be performed.

Strong

In case of very high risk or BCG unresponsive, radical cystectomy could be offered

Conditional

Treatment of MIBC

RC with standard PLND and protection of small intestine is the standard treatment of MIBC T2-T4a, N0 M0.

Strong

Patients with radiological suspicious node-positive disease (cN1) should be considered for preoperative platinum-based chemotherapy, however surgery can be offered in selected cases (e.g. unfit for systemic therapy, patient preference)

Strong

Organ-preservation therapy with radiotherapy, as part of multimodal schema for MIBC, is a reasonable option for patients with solitary tumors <7cm with no or unilateral hydronephrosis, and no extensive carcinoma in situ, also for patients seeking an alternative to RC and those who are medically unfit for surgery

Conditional

Contemporary organ-preservation protocols should utilize tri-modality combination of TURBT, radiotherapy and chemotherapy

Strong

Following completion of bladder preserving therapy, clinicians should perform regular surveillance with computed tomography (CT) scans, cystoscopy, and urine cytology.

Strong

Three to four cycles of cisplatin-based neoadjuvant chemotherapy should be given for MIBC

Strong

The use of adjuvant cisplatin-based Chemotherapy in patients with pathologic T3, T4, N+ after cystectomy who did not receive neoadjuvant therapy   should be considered

Strong

ddMVAC with growth factor support is the preferred regimen in the neoadjuvant setting , however Gemcitabine and cisplatin is a reasonable alternative

Strong

Carboplatin should not be substituted for cisplatin in the perioperative setting

Strong

For patients who are not candidates for cisplatin , there are no data to support a recommendation for perioperative chemotherapy

Strong

Standard radical cystectomy with curative intent need to obtain negative margins and should include removal of the bladder, prostate, and seminal vesicles in males; bladder in females and should consider removal of adjacent reproductive organs based on individual disease characteristics.

Bilateral pelvic lymphadenectomy should include removal of a minimum, the external and internal iliac and obturator lymph nodes.

Strong

Indications of Adjuvant radiotherapy after cystectomy

1-      P T3 / T4 MIBC

2-      Pathologically node positive

3-      Positive margins 

Strong

Postoperative adjuvant RT

Postoperative adjuvant RT : Treatment field should encompass areas at risk for harboring residual microscopic disease based on pathologic findings at resection and include resection bed, and  lymph nodes. Areas at risk for harboring residual microscopic disease should receive 45–50.4 Gy EBRT. Involved resection margins and areas of extranodal extension should be boosted to 54–60 Gy if feasible based on normal tissue constraints. Areas of gross residual disease should be boosted to 66–70 Gy, if feasible based on normal tissue constraints. Concurrent chemotherapy with regimens used for bladder cancer can be considered for added tumor cytotoxicity

Strong

Treatment of advanced/metastatic disease

First line systemic therapy

For Cisplatin eligible patients, gemcitabine and cisplatin or dd-MVAC (with growth factor support) regimens should be used

Strong

For Cisplatin ineligible patients, gemcitabine and carboplatin regimens should be used

Strong

Second and subsequent lines of therapy

Patients with good PS  

Second  line of therapy should  include either single agents as  gemcitabine, paclitaxel or docetaxel, or combination regimens as Gemcitabine and paclitaxel, or Ifosfamide, doxorubicin, and  gemcitabine   or other combinations

Strong

In patients with  progression free survival > 12 months after platinum ( cisplatin or carboplatin ), consider re-treatment with platinum if the patient is still platinum eligible

Conditional

 Palliative RT can be offered for palliation (bleeding, pain).

Strong