Urothelial Carcinoma of Bladder and Upper Tract Page 1 of 18 Disclaimer: This algorithm has been developed for MD Anderson using a multidisciplinary approach considering circumstances particular to MD Anderson’s specific patient population, services and structure, and clinical information. This is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient's care. This algorithm should not be used to treat pregnant women. Note: Consider Clinical Trials as treatment options for eligible patients. CLINICAL INITIAL INITIAL INITIAL SCREEN PRESENTATION EVALUATION DIAGNOSIS STAGING Negative for Treat as indicated3 bladder cancer Less than T2 See Page 2-3 ● Hematuria ● History and physical ● Transurethral resection (TUR) ● Recurrent unexplained 1 ● Office cystoscopy ● Exam under anesthesia (EUA) urinary tract infection Positive for ● Imaging: CT urogram or ● Consider single dose peri- ● Other unexplained bladder cancer 4 intravenous urogram (IVU) operative chemotherapy lower urinary tract 2 ● Lifestyle risk assessment instillation symptoms T2-4 See Page 4 (muscle invasion) Positive for See Page 6 upper tract tumor 1 Consider urinary cytology or other MD Anderson approved genitourinary biomarkers 2 See Physical Activity, Nutrition, and Tobacco Cessation algorithms; ongoing reassessment of lifestyle risks should be a part of routine clinical practice 3 If persistant microhematuria, recommend repeat of history and physical, office cystoscopy, imaging (CT urogram or IVU) in 2-3 years 4 Refer to Principles of Intravesical Treatment on Page 8 Department of Clinical Effectiveness V9 Approved by The Executive Committee of the Medical Staff on 07/21/2020 Urothelial Carcinoma of Bladder and Upper Tract Page 2 of 18 Disclaimer: This algorithm has been developed for MD Anderson using a multidisciplinary approach considering circumstances particular to MD Anderson’s specific patient population, services and structure, and clinical information. This is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient's care. This algorithm should not be used to treat pregnant women. Note: Consider Clinical Trials as treatment options for eligible patients. STAGE TREATMENT AND FOLLOW-UP No Ta-Unifocal TUR and surveillance cystoscopy1 at 3 months and if clear, then (low-grade Recurrence? 9 months later (at 12 months after initial), and then annually solitary tumor) Yes ● Ta: Follow Ta - Multifocal path Yes ● BCG (weekly for 6 weeks) with or without maintenance or Repeat cystoscopy to ● Tis, T1-3: Follow appropriate path Ta- ● Intravesical chemotherapy with maintenance for 1 year or assess response (with Residual Multifocal ● Observation13 (in selected cases) or or without biopsy if diease? (low-grade) 1 ● Clinical trial indicated) at 3 months Continue surveillance cystoscopy (every 3 months for No 2 years; every 6 months for 2 years; then annually) ● Radical cystectomy or ● Clinical trial or See Surveillance on Page 7 ● Salvage intravesical therapy or Yes 2 Persistent ● Pembrolizumab BCG (weekly for 6 weeks) Cystoscopy1 at Carcinoma carcinoma in-situ at plus maintenance for 3 years 3 and 6 months In-Situ (CIS) 6 months? No ● Continue BCG as per SWOG protocol 1 ● Continue surveillance cystoscopy (every 3 months for 2 years; every 6 months BCG = Bacillus Calmette-Guerin therapy SWOG = Southwest Oncology Group for 2 years; then annually) 1 Cystoscopy combined with either cytology or fluorescence in situ hybridization (FISH) cytology as indicated. In selected patients, fluorescent cystoscopy should be considered. 2 Pembrolizumab is indicated for the treatment of patients with BCG–unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy Department of Clinical Effectiveness V9 Approved by The Executive Committee of the Medical Staff on 07/21/2020 Urothelial Carcinoma of Bladder and Upper Tract Page 3 of 18 Disclaimer: This algorithm has been developed for MD Anderson using a multidisciplinary approach considering circumstances particular to MD Anderson’s specific patient population, services and structure, and clinical information. This is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient's care. This algorithm should not be used to treat pregnant women. Note: Consider Clinical Trials as treatment options for eligible patients. STAGE TREATMENT AND FOLLOW-UP ● Radical See cystectomy or Surveillance Consider Yes ● Clinical trial or ● Cystoscopy 1 on Page 7 repeating BCG (weekly for ● Pembrolizumab ● Consider repeat biopsy to resection in 6 weeks) plus Residual cTa assess response at 3 months 4-6 weeks, maintenance for disease? ● Continue BCG as per (if positive cystoscopy or no especially 3 years SWOG protocol initial TUR) Yes with T1 No ● Continue surveillance High- 2 Muscle cystoscopy (every 3 months Grade (HG) Ta in pathology for 2 years; every 6 months or T1- specimen? for 2 years; then annually) Unifocal No ● T1: re-biopsy No to exclude T2 Consider early Patient ● Ta, HG: cT1 cystectomy accepts pT3a Observation consider surgery? re-biopsy Yes Yes pT3b Consider adjuvant Upstaged Cystectomy cisplatin or at surgery? ifosfamide- N+, margins cT2 See Page 4 based positive or chemotherapy High risk T13 prostatic stromal No invasion pT4a (see Page 9) BCG = Bacillus Calmette-Guerin therapy SWOG = Southwest Oncology Group Observation 1 Pembrolizumab is indicated for the treatment of patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy 2 Cystoscopy combined with either cytology or fluorescence in situ hybridization (FISH) cytology as indicated. In selected patients, fluorescent cystoscopy should be considered. 3 T1 multifocal, variant histology with concurrent carcinoma in situ (CIS), lymphovascular invasion (LVI) and/or resectable tumor 3 cm or greater with poor prognosticator or too large to resect completely Department of Clinical Effectiveness V9 Approved by The Executive Committee of the Medical Staff on 07/21/2020 Urothelial Carcinoma of Bladder and Upper Tract Page 4 of 18 Disclaimer: This algorithm has been developed for MD Anderson using a multidisciplinary approach considering circumstances particular to MD Anderson’s specific patient population, services and structure, and clinical information. This is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient's care. This algorithm should not be used to treat pregnant women. Note: Consider Clinical Trials as treatment options for eligible patients. STAGE TREATMENT AND FOLLOW-UP See Assess response by: Surveillance ● Neoadjuvant Yes Radical cystectomy 2 ● Cystoscopy on Page 7 chemotherapy Resectable? ● EUA ● Clinical trial ● Imaging Consider cystectomy if No Salvage therapy surgically resectable ● EUA ● CT chest, Yes Presence pT3a Observation abdomen, and T2/3a, of poor risk pelvis N0, M0 factors1? ● CT chest if Yes pT3b T2-4 positive chest No ● Adjuvant cisplatin or (muscle x-ray or clinical Upstaged ifosfamide-based chemotherapy Cystectomy N+, margins positive invasion) suspicion for at surgery? (see Page 9) or or prostatic stromal metastasis Yes ● Clinical trial ● Bone scan if Patient invasion pT4a elevated alkaline accepts phosphatase or surgery? No Observation Bladder sparing treatment bone pain No ● Chemoradiation or ● Clinical trial T3b/4a, ● Neoadjuvant chemotherapy2 N0, M0 ● Clinical trial See Assess response by: Yes Radical cystectomy Surveillance ● Cystoscopy Resectable? on Page 7 1 Poor risk factors: ● EUA ● Lymphovascular invasion T4b, Consider metastatic chemotherapy ● Imaging No Additional chemotherapy ● Inability to assess depth of invasion N0, M0 clinical trial if available ● Variant histology such as small cell ● Hydronephrosis ● Tumor involving bladder diverticulum 2 Consider neoadjuvant/adjuvant cisplatin or ifosfamide-based systemic chemotherapy (i.e., DDMVAC, IAG, etc.). Refer to Principles of Systemic Therapy on Page 8 Department of Clinical Effectiveness V9 Approved by The Executive Committee of the Medical Staff on 07/21/2020 Urothelial Carcinoma of Bladder and Upper Tract Page 5 of 18 Disclaimer: This algorithm has been developed for MD Anderson using a multidisciplinary approach considering circumstances particular to MD Anderson’s specific patient population, services and structure, and clinical information. This is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient's care. This algorithm should not be used to treat pregnant women. Note: Consider Clinical Trials as treatment options for eligible patients. Surgical CLINICAL PRESENTATION METASTATIC DISEASE See Surveillance consolidation Yes on Page 7 trials 2 ● Chemotherapy ● CT chest, Assess response by: Resectable ? ● Positive pelvic nodes or ● Consider metastatic