|Year : 2018 | Volume
| Issue : 2 | Page : 133-137
Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder 2017
Hulayel Alharbi1, Sultan Alkhateeb2, Esam Murshid3, Mohammed Alotaibi4, Ashraf Abusamra5, Danny Rabah6, Mubarak Almansour7, Abdullah Alghamdi8, Ali Aljubran9, Amin Eltigani10, Hussein Alkushi11, Imran Ahmed12, Abdullah Alsharm13, Shouki Bazarbashi9
1 Department of Medical Oncology, King Fahed Specialist Hospital, Dammam, Saudi Arabia
2 Department of Surgery, Division of Urology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
3 Department of Oncology, Oncology Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
4 Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
5 Department of Surgery, Urology Section, King Khalid Hospital, King Abdulaziz Medical City, 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, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
8 Department of Urology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
9 Oncology Center, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
10 Department of Oncology, Division of Medical Oncology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
11 Department of Pathology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
12 Department of Oncology, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
13 Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
|Date of Submission||18-Nov-2017|
|Date of Acceptance||18-Dec-2011|
|Date of Web Publication||09-Apr-2018|
Dr. Shouki Bazarbashi
Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh 11211
| Abstract|| |
This is an update to the previously published Saudi guidelines for the evaluation and medical/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 their accompanying supporting evidence level, which is 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 policymakers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.
Keywords: Carcinoma, Guidelines, management, Saudi Oncology Society, Saudi Urological Association, urothelial
|How to cite this article:|
Alharbi H, Alkhateeb S, Murshid E, Alotaibi M, Abusamra A, Rabah D, Almansour M, Alghamdi A, Aljubran A, Eltigani A, Alkushi H, Ahmed I, Alsharm A, Bazarbashi S. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder 2017. Urol Ann 2018;10:133-7
|How to cite this URL:|
Alharbi H, Alkhateeb S, Murshid E, Alotaibi M, Abusamra A, Rabah D, Almansour M, Alghamdi A, Aljubran A, Eltigani A, Alkushi H, Ahmed I, Alsharm A, Bazarbashi S. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder 2017. Urol Ann [serial online] 2018 [cited 2018 Aug 18];10:133-7. Available from: http://www.urologyannals.com/text.asp?2018/10/2/133/229561
| Introduction|| |
According to the cancer incidence report in Saudi Arabia for the year 2013, there were 280 new cases of urinary bladder cancer, accounting for 4.3% and 0.8% of all newly diagnosed cases of cancer in men and women, respectively. Urinary bladder cancer is ranked the 8th most common cancer in males and the 20th most common in females. Of the 280 cases, 227 affected males (81%) and 53 affected females (19%). The overall age-standardized incidence rate was 3.8/100,000, in males and 1/100,000 in females. The median age at diagnosis was 63 years among males and 64 years among females.
| Staging|| |
The American Joint Committee on Cancer tumor, nodes, metastases staging definitions for bladder cancer should be used  [Table 1] and [Table 2].
|Table 1: Tumor, node, and metastasis staging for urothelial bladder carcinoma|
Click here to view
|Table 2: Urothelial bladder carcinoma anatomical stages and prognostic groups|
Click here to view
| Tumor Grading|| |
The 2016 World Health Organization Classification of Tumors of the Urinary System  will be used as follows:
- Noninvasive urothelial lesions
- Urothelial carcinoma in situ
- Papillary urothelial carcinoma, low grade
- Papillary urothelial carcinoma, high grade
- Papillary urothelial neoplasm of low malignant potential.
- Urothelial papilloma
- Inverted urothelial papilloma
- Urothelial proliferation of uncertain malignant potential (hyperplasia)
- Urothelial dysplasia
- Invasive urothelial tumor.
| Pathology Reporting|| |
Surgical pathology reporting must include the following:
- 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 variant.
| Evaluation of the Bladder Tumor|| |
The initial evaluation should include history and physical examination, complete blood count, renal function, urine cytology, and bladder ultrasonography. Initial diagnostic cystoscopy should be done with transurethral bladder tumor resection (TURBT) to achieve complete resection if possible. Imaging of the upper tract should be done by ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) urogram. If the cystoscopy findings confirm the invasive disease, do CT or MRI of abdomen and pelvis, as well as chest imaging.,
| Management Of Nonmuscle Invasive Urothelial Bladder Carcinoma|| |
- If the findings of the diagnostic cystoscopy are suggestive of a noninvasive bladder tumor
- Conduct TURBT to achieve complete resection, if possible
- Repeat TURBT within 2–4 weeks, indicated if the resection was incomplete, the disease is high-grade Ta or T1, or if no muscle examination was performed
- Administer a single postoperative instillation of intravesical chemotherapy (e.g., mitomycin C or epirubicin/doxorubicin) within 24 h of TURBT, unless perforation is suspected ,,
- Provide further treatment according to risk stratification.
- Risk stratification for nonmuscle invasive urothelial bladder carcinoma
- Risk depends on the following factors: T stage, the presence of CIS, grade, recurrence rate, number of tumors, and tumor size  [Table 3]
- 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).
- Management of low-risk NMIBC– Surveillance cystoscopy (3–6 months) intervals [Table 4]
- Management of intermediate risk NMIBC:
- Intravesical bacillus Calmette–Guerin (BCG) or mitomycin induction (weekly for 6 weeks)
- Surveillance cystoscopy and cytology
- Upper tract imaging every 2 years or as indicated.
- Management of high-risk nonmuscle, invasive bladder cancer, including carcinoma in situ
- Intravesical BCG or mitomycin induction (weekly for 6 weeks) and maintenance therapy (3 weekly injections) at 3, 6, 12, 18, 24, 30, and 36 months from induction ,
- 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 inductions of adjuvant intravesical therapy were given before, then consider changing the intravesical therapy
- Consider early cystectomy in recurrent CIS, T1, and high-grade disease with prior treatment with no >2 inductions 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, MRI, or retrograde pyelogram)
- Ureteroscopy if suspicion of upper tract tumor.
|Table 3: Risk stratification for nonmuscle invasive urothelial bladder carcinoma|
Click here to view
| Management Of Muscle-Invasive Urothelial Bladder Carcinoma|| |
Staging should include complete blood count; renal function; serum electrolytes; liver function test, including alkaline phosphatase; imaging of the chest, abdomen, and pelvis (CT or MRI); and a bone scan if elevated alkaline phosphatase or symptoms of bone pain are present.
- 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, the common, internal and external iliac, and obturator nodesBladder preservation with trimodality combination of complete resection of the bladder tumor TURBT, followed by concurrent chemoradiation with early radical cystectomy in failure, are alternatives to upfront radical cystectomy ,,,,, in selected patients with solitary disease, no CIS, no hydronephrosis, normal renal function, and adequate bladder capacity In patients undergoing bladder preservation, early evaluation by cystoscopy with or without biopsy is recommended after 40–45 Gy for the whole bladder and regional nodes. If there is residual/recurrent tumor, then consider cystectomy. If there is complete response, then complete radiotherapy to 60–65 Gy total dose in conventional fractionation; altered fractionation regimens, such as 50–52.5 Gy in 20 fractions, may also be considered For patients who are not candidates for radical treatment, consider TURBT and/or palliative radiotherapyIf no neoadjuvant chemotherapy is given, consider adjuvant cisplatin-based chemotherapy following pathological criteria (pT3–4, positive nodes).
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 (performance status [PS] 0–2) are treated with combination cisplatin and gemcitabine for a maximum of six cycles 
- Patients with decreased renal function and/or unfit (PS 3) are treated with combination of carboplatin and gemcitabine  or single-agent gemcitabine, carboplatin, or atezolizumab 
- There is no standard, second-line therapy; patients who relapse or progress on the first-line may be given atezolizumab, vinflunine, or taxanes as second-line chemotherapy
- Patients who present with local recurrence may benefit from palliative radiation therapy.
Financial support and sponsorship
Funding was provided by the Saudi Oncology Society for this work.
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.
Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: Prostate and bladder tumours. Eur Urol 2016;70:106-19.
Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: Renal, penile, and testicular tumours. Eur Urol 2016;70:93-105.
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;171:2186-90.
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.
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.
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.
Grimm MO, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA, et al.
Effect of routine repeat transurethral resection for superficial bladder cancer: A long-term observational study. J Urol 2003;170:433-7.
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.
Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J, et al.
EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2008;54:303-14.
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.
Persad R, Lamm D, Brausi M, Soloway M, Palou J, Böhle 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.
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.
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.
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.
Matzkin H, Soloway MS, Hardeman S. Transitional cell carcinoma of the prostate. J Urol 1991;146:1207-12.
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.
Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis. Lancet 2003;361:1927-34.
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.
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.
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, 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.
Rödel C, Weiss C, Sauer R. Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 2006;24:5536-44.
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;69:80-92.
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 2015;94:105-15.
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.
Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al.
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 2016;387:1909-20.
[Table 1], [Table 2], [Table 3], [Table 4]