|Year : 2011 | Volume
| Issue : 4 | Page : 6-9
Saudi Oncology Society clinical management guidelines for urinary bladder cancer
Khaled Al Othman, Shouki Bazarbashi, Khalid Balaraj, Mohamed Al Otaibi, Baher Kamal, Ibraheem Al Oraifi, Eyad Al Saeed, Khalid Al Gamdi, Ali Jubran, Ahmad Salah, Jalal Al Shareef, Jamal Zekri
Department of Urology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
|Date of Web Publication||2-Apr-2011|
Khaled Al Othman
Department of Urology, POBOX 3354 MBC 83, King Faisal Specialist Hospital and Research Center, Riyadh - 11211
| Abstract|| |
In this report guidelines for the evaluation, medical and surgical management of transitional cell carcinoma of urinary bladder is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7 th edition. The recommendations are presented with supporting level of evidence.
Keywords: Urinary bladder cancer, Saudi, guidelines
|How to cite this article:|
Al Othman K, Bazarbashi S, Balaraj K, Al Otaibi M, Kamal B, Al Oraifi I, Al Saeed E, Al Gamdi K, Jubran A, Salah A, Al Shareef J, Zekri J. Saudi Oncology Society clinical management guidelines for urinary bladder cancer. Urol Ann 2011;3, Suppl S1:6-9
|How to cite this URL:|
Al Othman K, Bazarbashi S, Balaraj K, Al Otaibi M, Kamal B, Al Oraifi I, Al Saeed E, Al Gamdi K, Jubran A, Salah A, Al Shareef J, Zekri J. Saudi Oncology Society clinical management guidelines for urinary bladder cancer. Urol Ann [serial online] 2011 [cited 2018 May 23];3, Suppl S1:6-9. Available from: http://www.urologyannals.com/text.asp?2011/3/4/6/78549
| Introduction|| |
There were 211 cases of bladder cancer accounting for 2.6% of all newly diagnosed cases in the year 2006 in Saudi Arabia. This cancer ranked ninth among male population and twentieth among female population. It affected 169 (80.1%) males and 42 (19.9%) females with a male to female ratio of 4:1. The overall ASR was 2.6/100,000; 4.1/100,000 for males and 1/100,000 for female. 
| 1. Staging|| |
See Appendix I
| 2. Grading|| |
The World Health Organization (WHO) grading of urinary tumors 2004  will be used as follows:
2.1. Urothelial papilloma
2.2. PUNLMP: Papillary urothelial neoplasm of low malignant potential
2.3. Low-grade papillary urothelial carcinoma
2.4. High-grade papillary urothelial carcinoma
| 3. Non-Muscle Invasive Bladder Cancer (Ta, T1, TIS)|| |
3.1. Evaluation should include:
3.1.1. History and physical examination
22.214.171.124. For non-muscle invasive tumors, imaging of upper urinary tract (CT or IVU) is indicated if patient has tumors located in the trigone, multifocal or high-risk tumors (see item 3.2.3). , (EL3)
126.96.36.199. CT abdomen/pelvis or MRI and CXR or CT chest is indicated for staging of muscle invasive bladder tumor. (EL3)
3.1.3. Urine cytology
3.1.4. Cystoscopy, which should include:
188.8.131.52. Transurethral resection of bladder tumors (TURBT): The following should be observed:
184.108.40.206.1. The goal of TURBT is to define the stage and grade of tumor (diagnostic) and to resect all grossly visible tumors (therapeutic).
220.127.116.11.2. Deep resection is important to assess the depth of tumor invasion to the muscle.
18.104.22.168.3. Random bladder and prostatic urethral biopsies are indicated only in patients with positive urine cytology with normal appearing bladder. ,, (EL3)
22.214.171.124.4. Second TURBT is recommended to be done within 2-6 weeks from initial resection in the following conditions: ,, (EL2)
126.96.36.199.4.1. Incomplete initial resection
188.8.131.52.4.2. No muscle tissue in initial resection specimen
184.108.40.206.4.3. High-grade NMIBT (Non-muscle invasive bladder tumor)
220.127.116.11.4.4. T1 bladder tumor
3.2. Risk stratification for non-muscle invasive bladder cancer: This depends on the following factors: tumor stage, grade, presence of carcinoma in situ, number of tumors, tumor size and prior recurrence rate: 
3.2.1. Low-risk NMIBC (small volume, low-grade Ta)
3.2.2. Intermediate risk NMIBC (multifocal and/or large-volume low-grade Ta, recurrence at 3 months)
3.2.3. High-risk NMIBC (high-grade Ta, all T1, CIS)
3.3. Intravesical therapy:
3.3.1. Low-risk tumors: A single immediate post-operative instillation of mitomycin C or doxorubicin within 24 h (preferably within 6 h) if no suspicion of bladder perforation should be considered.  (EL1)
3.3.2. Intermediate risk: it is recommended to give single immediate instillation of chemotherapy followed by induction BCG.  (EL2)
3.3.3. High risk
18.104.22.168. Carcinoma in situ:
22.214.171.124.1. It is recommended to give induction intravesical BCG plus maintenance for at least 1 year. , (EL1)
126.96.36.199.2. Assess response at 3 months, if no response:
188.8.131.52.2.1. Additional 6 weeks course of BCG or
184.108.40.206.2.2. Radical cystectomy or
220.127.116.11.2.3. If no complete response at 6 months, radical cystectomy. 
18.104.22.168. Multiple high-grade Ta-T1:
22.214.171.124.1. It is recommended to repeat TURBT at 2-6 weeks, after initial resection.
126.96.36.199.2. Intravesical BCG induction plus maintenance for at least 1 year.
188.8.131.52.3. Immediate radical cystectomy can be considered for highest risk patients (T1 high grade with or without CIS)  . (EL3)
3.4. Treatment of intravesical therapy failure:
3.4.1. Definition of intravesical therapy failure: 
184.108.40.206. Whenever muscle invasion is detected during follow up.
220.127.116.11. If high-grade non-muscle invasive bladder cancer is present at 3 or 6 months.
18.104.22.168. Any worsening of the disease with BCG treatment like higher stage or grade or appearance of CIS.
3.4.2. Management of intravesical therapy failure:
22.214.171.124. Patients with recurrence of NMIBC following immediate intravesical chemotherapy may benefit from BCG treatment.
126.96.36.199. Patients with initial BCG therapy failure who experience recurrence of high-grade disease at 6 months should be offered cystectomy. 
188.8.131.52. In case of failure before maintenance BCG has been completed, cystectomy should be considered if high-grade T1 or CIS is present. But for high-grade Ta recurrences, repeat resection and induction intravesical therapy could be started.  (EL3)
3.5.1. Low risk: Cystoscopy and cytology at 3 months - if negative, next cystoscopy and cytology at 12 months and then yearly for 5 years. (EL3)
3.5.2. High risk: Cystoscopy and cytology at 3 months, if negative, following cystoscopies should be repeated every 3 months for 2 years, at every 4 months in the third year and then every 6 months until 5 years and annually thereafter.
3.5.3. Intermediate risk: Similar to high risk, however schedule can be adapted according to individual patient. 
3.5.4. Annual imaging of upper urinary tract in high-risk group
| 4. Muscle Invasive Bladder Cancer: Options Include|| |
4.1. Radical cystectomy and urinary diversion:
4.1.1. Radical cystectomy is the preferred curative treatment for localized bladder cancer (EL3)
4.1.2. Radical cystectomy includes removal of regional lymph nodes, the extent of which has not been sufficiently defined (EL3)
4.1.3. Laparoscopic and robotic radical cystectomy are optional
4.1.4. An orthotopic bladder substitute option should be offered to male and female patients lacking any contra-indications.
4.1.5. Neoadjuvant cisplatin-based chemotherapy improved overall survival by 5-7% at 5 years and this option should be offered to patients especially with locally advanced disease (T3,T4). ,, (EL1)
4.1.6. Follow-up after radical cystectomy:
184.108.40.206. Urine cytology, creatinine, electrolytes, every 3 to 9 months for 2 years and then as clinically indicated. 
220.127.116.11. CT chest, abdomen and pelvis every 3 to 9 months for 2 years based on risk of recurrence and as clinically indicated.
18.104.22.168. Urethral wash cytology, every 6 to 12 months. (EL3)
4.2. Radiation therapy should be offered for patients with localized disease not fit for surgery and chemotherapy. (EL3)
4.3. Bladder sparing treatment: multimodality treatment should be considered as an option for selected group of patients and well-informed compliant patients (EL3):
4.3.1. Patients selected for bladder sparing treatment should have the following:
22.214.171.124. Clinically T2-T3 tumor
126.96.36.199. No hydronephrosis
188.8.131.52. Normal renal function
184.108.40.206. No multifocal disease or carcinoma in situ
220.127.116.11. Functional bladder
18.104.22.168. Urothelial histology
22.214.171.124. No prostatic urethral involvement
4.3.2. Multimodality therapy should consist of:
126.96.36.199. Aggressive and visibly complete TURBT.
188.8.131.52. Concurrent cisplatin at 100 mg/m2 at day 1 and 22 of radiation therapy.
184.108.40.206. Radiation therapy at 1.8 Gy/fraction
220.127.116.11. Cystoscopy (within 2 weeks) after the initial phase (45 Gy): patients with positive biopsy or cytology should undergo radical cystectomy. Patients with negative results would continue radiation with a cone down beam for a total of 64.8 Gy and one more cycle of cisplatin.
4.3.3. Follow up should include cystoscopy every 3 months for the first 2 years, then every 6 months for the next 3 years and then annually.
4.3.4. Superficial recurrent disease should be treated locally (TURBT ± BCG). (EL3)
4.4. Adjuvant chemotherapy
4.4.1. Adjuvant chemotherapy could be considered using Cisplatin and gemcitabine regimen in patients with: 
18.104.22.168. Normal renal function.
22.214.171.124. Performance status 0-2.
126.96.36.199. Pathological stage T3, 4 or node-positive disease.
188.8.131.52. Patients should not have received neo-adjuvant chemotherapy.
184.108.40.206. Urothelial histology
| 5. Advanced, Metastatic and Recurrent Disease: Chemotherapy is the Mainstay of Therapy|| |
5.1. 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 (EL1). 
5.2. Patients with decreased renal function and / or unfit (PS 3) are treated with combination of Carboplatin and gemcitabine or single agent gemcitabine (EL2). 
5.3. Patient who relapse or progress on the above regimens may be given taxanes as second-line chemotherapy (EL2).
5.4. Patients who present with local recurrence may benefit from palliative radiation therapy
Appendix I: TNM Staging
[Additional file 1]
| References|| |
|1.||Saudi Cancer registry: Annual Report. 2006. |
|2.||Sobin DH WC: TNM Classification of Malignant Tumours. 6th Ed. New York: Wiley-Liss; 2002. p. 199-202. |
|3.||Eble JN SG, Epstein Jl, Sesterhenn I, editors. WHO classification of tumors of the urinary system and male genital organs. Lyon: IARCC Press 2004. p. 29-34. |
|4.||Palou J, Rodriguez-Rubio F, Huguet J, Segarra J, Ribal MJ, Alcaraz A, et al. Multivariate analysis of clinical parameters of synchronous primary superficial bladder cancer and upper urinary tract tumor. J Urol 2005;174:859-61. |
|5.||Millan-Rodriguez F, Chechile-Toniolo G, and Salvador-Bayarri J, Huguet-Pérez J, Vicente-Rodríguez J. Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. J Urol 2000;164:1183-7. |
|6.||Mungan MU, Canda AE, Tuzel E, Yorukoglu K, Kirkali Z. Risk factors for mucosal prostatic urethral involvement in superficial transitional cell carcinoma of the bladder. Eur Urol 2005;48:760-3. |
|7.||Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, et al. Bladder cancer: Epidemiology, staging and grading, and diagnosis. Urology 2005;66:4-34. |
|8.||Matzkin H, Soloway MS, Hardeman S. Transitional cell carcinoma of the prostate. J Urol 1991;146:1207-12. |
|9.||Grimm MO, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Effect of routine repeat transurethral resection for superficial bladder cancer: A long-term observational study. J Urol 2003;170:433-7. |
|10.||Divrik RT, Yildirim U, Zorlu F, Ozen H. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: A prospective, randomized clinical trial. J Urol 2006;175:1641-4. |
|11.||Jahnson S, Wiklund F, Duchek M, Mestad O, Rintala E, Hellsten S, et al. Results of second-look resection after primary resection of T1 tumour of the urinary bladder. Scand J Urol Nephrol 2005;39:206-10. |
|12.||Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49:466-5. |
|13.||Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol 2004;171:2186-90. |
|14.||Approaches to the Management of Non-Muscle Invasive Bladder Cancer (NMIBC): A Review of Current Guidelines and Best Practice Recommendations from the International Bladder Cancer Group (IBCG). 2008;7:615-674 |
|15.||Sylvester RJ, van der MEIJDEN AP, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: A meta-analysis of the published results of randomized clinical trials. J Urol 2002;168:1964-70. |
|16.||Bohle A, Bock PR. Intravesical bacille Calmette-Guerin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 2004;63:682-6. |
|17.||van der Meijden AP, Sylvester R, Oosterlinck W, Solsona E, Boehle A, Lobel B, et al. EAU guidelines on the diagnosis and treatment of urothelial carcinoma in situ. Eur Urol 2005;48:363-71. |
|18.||Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2008;54:303-14. |
|19.||Nieder AM, Brausi M, Lamm D, O'Donnell M, Tomita K, Woo H, et al. Management of stage T1 tumors of the bladder: International Consensus Panel. Urology 2005;66:108-25. |
|20.||Persad R, Lamm D, Brausi M, Soloway M, Palou J, Bohle A, et al. Current approaches to the management of non-muscle invasive bladder cancer: Comparison of current guidelines and recommendations. European Urology Supplements 2008;7:637-50. |
|21.||Winquist E, Kirchner TS, Segal R, Chin J, Lukka H. Genitourinary Cancer Disease Site Group, Cancer Care Ontario Program in Evidence-based Care Practice Guidelines Initiative. . Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: A systematic review and meta-analysis. J Urol 2004;171:561-9. |
|22.||Neoadjuvant chemotherapy in invasive bladder cancer: Update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48:202-5. |
|23.||Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis. Lancet 2003;361:1927-34. |
|24.||National Comprehensive Cancer Network. Clinical practice guidelines in oncology: Bladder cancer including upper tract tumors and urothelial carcinoma of the prostate. Version1. 2010. |
|25.||Ruggeri EM, Giannarelli D, Bria E, Carlini P, Felici A, Nelli F, et al. Adjuvant chemotherapy in muscle-invasive bladder carcinoma: A pooled analysis from phase III studies. Cancer 2006;106:783-8. |
|26.||von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23:4602-8. |
|27.||De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, et al. Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. J Clin Oncol 2009;27:5634-9. |