|Year : 2016 | Volume
| Issue : 2 | Page : 131-135
Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder
Sultan Alkhateeb1, Mubarak Al-Mansour2, Mohammed Alotaibi3, Ahmad Saadeddin4, Ashraf Abusamra5, Danny Rabah6, Esam Murshid7, Abdullah Alsharm8, Imran Ahmad9, Hussain Kushi10, Abdullah Alghamdi11, Khalid Alghamdi12, Shouki Bazarbashi13
1 Department of Surgery, Division of Urology, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Oncology, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
3 Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4 Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
5 Department of Surgery, Urology Section, King Khalid Hospital, King Abdulaziz Medical City, Ministry of Nati onal Guard Health Affairs, Jeddah, Saudi Arabia
6 Department of Surgery, College of Medicine and Uro-Oncology Research Chair, King Saud University, Riyadh, Saudi Arabia
7 Department of Oncology, Oncology Center, Prince Sultan Medical Military City, Jeddah, Saudi Arabia
8 Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
9 Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
10 Department of Radiation Oncology, Princess Norah Oncology Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia
11 Department of Urology, Prince Sultan Medical Military Center, Jeddah, Saudi Arabia
12 Department of Surgery, Division of Urology, Security Forces Hospital, Riyadh, Saudi Arabia
13 Department of Oncology, Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
|Date of Submission||08-Nov-2015|
|Date of Acceptance||15-Nov-2015|
|Date of Web Publication||23-Mar-2016|
Department of Surgery, Division of Urology, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, P.O. Box: 22490 (1446), Riyadh 11426
| Abstract|| |
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 7th 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.
Keywords: Guidelines, management, Saudi Oncology Society, Saudi Urological Association, urothelial carcinoma
|How to cite this article:|
Alkhateeb S, Al-Mansour M, Alotaibi M, Saadeddin A, Abusamra A, Rabah D, Murshid E, Alsharm A, Ahmad I, Kushi H, Alghamdi A, Alghamdi K, Bazarbashi S. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder. Urol Ann 2016;8:131-5
|How to cite this URL:|
Alkhateeb S, Al-Mansour M, Alotaibi M, Saadeddin A, Abusamra A, Rabah D, Murshid E, Alsharm A, Ahmad I, Kushi H, Alghamdi A, Alghamdi K, Bazarbashi S. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder. Urol Ann [serial online] 2016 [cited 2019 Nov 15];8:131-5. Available from: http://www.urologyannals.com/text.asp?2016/8/2/131/176873
| 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).
| Staging|| |
The staging is shown in [Appendix 1 [Additional file 1].
| Grading|| |
The World Health Organization grading of urinary tumors 2004 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.
| 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 
- 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),
- 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.,,
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:
- 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).
Surveillance cystoscopy (3–6 months) intervals [Appendix 2 [Additional file 2].
- Adjuvant intravesical (6-week induction) bacillus Calmette–Guerin (BCG) (preferred) or mitomycin 
- 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[Additional file 3]],
- Close surveillance cystoscopy, cytology, and upper tract imaging
- Consider early cystectomy in selected patients.
Recurrence of nonmuscle invasive disease
- Adjuvant intravesical therapy if not given before or as a second induction 
- 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.,
Positive urine cytology without gross evidence of disease
- Multiple biopsies of the bladder and prostatic urethra ,,
- 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.
Clinical T2–T4a disease with negative lymph nodes
- Neoadjuvant cisplatin-based combination chemotherapy ,,
- Considered in clinical T2
- Strongly recommended in clinical T3.
- Radical cystectomy with extended lymphadenectomy (open, laparoscopic, or Robotic) is considered the standard treatment 
- 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 ,,,,, in selected patients with solitary disease, no CIS, no hydronephrosis, normal renal function, and adequate bladder capacity 
- 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 
- 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.
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.
- 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 
- Patients with decreased renal function and/or unfit (PS 3) are treated with combination of Carboplatin and gemcitabine or single agent gemcitabine or carboplatin 
- 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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL. AJCC Cancer Staging Manual. 7th
ed. New York: Springer; 2010. p. 497-505.
Eble JN, Sauter G, Epstein JL, Sesterhenn I, editors. WHO classification of tumors of the urinary system and male genital organs. Lyon: IARC Press; 2004. p. 29-34.
Amin MB, McKenney JK, Paner GP, Hansel DE, Grignon DJ, Montironi R, et al.
ICUD-EAU international consultation on bladder cancer 2012: Pathology. Eur Urol 2013;63:16-35.
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 (6 Pt 1):2186-90.
Palou J, Rodríguez-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.
Millán-Rodríguez F, Chéchile-Toniolo G, 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.
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 (2 Pt 1):433-7.
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.
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.
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.
Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BW, Compérat E, et al.
EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2013. Eur Urol 2013;64:639-53.
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.
Böhle A, Bock PR. Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: Formal meta-analysis of comparative studies on tumor progression. Urology 2004;63:682-6.
Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J; European Association of Urology (EAU). EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2008;54:303-14.
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. Eur Urol Suppl 2008;7:637-50.
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.
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 6 Suppl 1:108-25.
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.
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 6 Suppl 1:4-34.
Matzkin H, Soloway MS, Hardeman S. Transitional cell carcinoma of the prostate. J Urol 1991;146:1207-12.
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 (2 Pt 1):561-9.
Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. 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.
Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis. Lancet 2003;361:1927-34.
Gakis G, Efstathiou J, Lerner SP, Cookson MS, Keegan KA, Guru KA, et al.
ICUD-EAU international consultation on bladder cancer 2012: Radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2013;63:45-57.
Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI. Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol 2010;28:4912-8.
James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, et al
. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N
Engl J Med 2012;366:1477-88.
Rödel C, Weiss C, Sauer R. Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 2006;24:5536-44.
Rödel C, Grabenbauer GG, Kühn R, Papadopoulos T, Dunst J, Meyer M, et al.
Combined-modality treatment and selective organ preservation in invasive bladder cancer: Long-term results. J Clin Oncol 2002;20:3061-71.
Shipley WU, Zietman AL, Kaufman DS, Coen JJ, Sandler HM. Selective bladder preservation by trimodality therapy for patients with muscularis propria-invasive bladder cancer and who are cystectomy candidates – the Massachusetts General Hospital and Radiation Therapy Oncology Group experiences. Semin Radiat Oncol 2005;15:36-41.
Milosevic M, Gospodarowicz M, Zietman A, Abbas F, Haustermans K, Moonen L, et al.
Radiotherapy for bladder cancer. Urology 2007;69 1 Suppl:80-92.
Arcangeli G, Arcangeli S, Strigari L. A systematic review and meta-analysis of clinical trials of bladder-sparing trimodality treatment for muscle-invasive bladder cancer (MIBC). Crit Rev Oncol Hematol 2014;14:1040-50.
Leow JJ, Martin-Doyle W, Rajagopal PS, Patel CG, Anderson EM, Rothman AT, et al.
Adjuvant chemotherapy for invasive bladder cancer: A 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 2014;66:42-54.
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.
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.