Brazilian consensus in muscle-invasive and metastatic urothelial carcinoma

Authors: Andrey Soares1,2, Icaro Carvalho2,3, Diogo Assed Bastos4, Diogo Augusto Rodrigues da Rosa5, Fernando Cotait

Maluf2,6,7, Ari Adamy Junior8, Daher Chade9, Luis Felipe Piovesan10, Allison Bruno Barcelos Borges11, Arthur

Acciolly12,13,14, Lucas Nogueira15.

Affiliations:

1. Centro Paulista de Oncologia, São Paulo, São Paulo, Brazil

2. Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil

3. Instituto Abathon, São Paulo, São Paulo, Brazil

4. Hospital Sírio-Libanês, São Paulo, São Paulo, Brazil

5. Grupo Oncoclínicas Rio de Janeiro, Rio de Janeiro, Brazil

6. Beneficência Portuguesa, São Paulo, São Paulo, Brazil

7. Hospital Santa Lúcia, Brasília, Distrito Federal, Brazil

8. Hospital Santa Casa de Curitiba, Curitiba, Paraná, Brazil

9. Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da USP, São Paulo, São Paulo, Brazil

10. CEPON - Centro de Pesquisas Oncológicas, Florianópolis, Santa Catarina, Brazil

11. Hospital DF Star - Rede D’or, Brasília, Distrito Federal, Brazil

12. Sociedade Brasileira de Radioterapia, São Paulo, São Paulo, Brazil

13. Hospital Português da Bahia, Salvador, Bahia, Brazil

14. Hospital São Rafael, Salvador, Bahia, Brazil

15. Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

TREATMENT SELECTION

1. Glomerular filtration rate limit to consider the patient eligible to receive cisplatin-based chemotherapy is:

a. 60 mL/min: 58.3%

b. 50 mL/min: 37.5%

c. 40 mL/min: 4.2%

d. Abstention

1bis. Glomerular filtration rate limit to consider the patient eligible to receive cisplatin-based chemotherapy is:

a. 60 mL/min: 38.5%

b. 50 mL/min: 61.5%

c. 40 mL/min:0%

d. Abstention

2. Is PS2 or higher a criterion of ineligibility for cisplatin?

a. Yes: 65.2%

b. No: 34.8%

c. Abstention

2bis. Is PS2 or higher a criterion of ineligibility for cisplatin?

a. Yes: 80%

b. No: 20%

c. Abstention

3. Is significant hearing loss (Grade II or higher) a criterion of cisplatin ineligibility?

a. Yes: 84.6%

b. No: 15.4%

c. Abstention

4. Is peripheral neuropathy clinically significant (Grade II or higher) a criterion of cisplatin ineligibility?

a. Yes: 88%

b. No: 12%

c. Abstention

5. Congestive heart failure (CHF) class III or worse is a criterion for cisplatin ineligibility?

a. Yes: 100%

b. No: 0%

c. Abstention

6. The evaluation of PD-L1 expression is indicated:

a. In the diagnosis of muscle-invasive disease in all cases: 0%

b. In the diagnosis of metastatic disease before first-line treatment in all patients: 0%

c. In the diagnosis of metastatic disease before first-line treatment only in patients ineligible for cisplatin: 63.6%

d. After progression with first-line chemotherapy for all patients: 4.5%

e. After progression with first-line chemotherapy only in patients ineligible for cisplatin: 0%

f. I do not routinely request expression analysis of PD-L1: 31.8%

g. Abstention

6bis. Evaluation of PD-L1 expression is indicated:

a. In the diagnosis of muscle-invasive disease in all cases: 0%

b. In the diagnosis of metastatic disease before first-line treatment in all patients: 0%

c. In the diagnosis of metastatic disease before first-line treatment only in patients ineligible for cisplatin: 92%

d. After progression with first-line chemotherapy for all patients: 4%

e. After progression with first-line chemotherapy only in patients ineligible for cisplatin: 0%

f. I do not routinely request expression analysis of PD-L1: 4%

g. Abstention

7. The evaluation of FGFR mutations is indicated:

a. In the diagnosis of muscle-invasive disease in all cases: 0%

b. In the diagnosis of muscle-invasive disease before first-line treatment in all patients: 15.8%

c. After progression with first-line chemotherapy for all patients: 84.2%

d. The search for FGFR mutations should not be routinelyperformed : 0%

e. Abstention

8. The material for analysis of PD-L1 and FGFR can be made:

a. In the material of the first sampling (either of the initial disease or of the metastatic disease): 8.7%

b. Always prior to the use of immunotherapy: 4.3%

c. Preferably the most recent possible, however, there is no formal recommendation for a new biopsy: 87%

d. Abstention

NEOADJUVANT AND ADJUVANT TREATMENT -MUSCLE INVASIVE

UROTHELIAL CARCINOMA

9. In patients with localized bladder urothelial carcinoma (T2-T4a, N0) their preferred treatment is? a. Radical cystectomy followed by adjuvant chemotherapy if stage > T2N0: 11.1%

b. Multimodal therapy (maximum TUR, followed by RT + QT): 11.1%

c. Neoadjuvant chemotherapy followed by radical cystectomy: 77.8%

d. Abstention

10. In patients with locally advanced bladder urothelial carcinoma (Tx, N+) their preferably treatment is? a. Surgery followed by adjuvant chemotherapy: 0%

b. Isolated chemotherapy: 8.1%

c. Chemotherapy followed by radical cystectomy and lymphadenectomy: 86.5%

d. Multimodal therapy (maximum TUR, followed by RT + QT): 5.4%

e. Abstention

11. Regarding the use of neoadjuvant chemotherapy in the treatment of muscle-invasive urothelial carcinoma: a. I indicate in all patients regardless of eligibility for cisplatin: 9.1%

b. I indicate in all non-metastatic patients which are candidates for cisplatin: 48.5%

c. I indicate only in selected cases (≥T3 or T2 with vascular invasion) and candidates for cisplatin: 36.4%

d. I do not routinely indicate and I refer for adjuvant chemotherapy after surgery: 6.1%

e. Abstention

11bis. Regarding the use of neoadjuvant chemotherapy in the treatment of muscle-invasive urothelial carcinoma: a. I indicate in all patients regardless of eligibility for cisplatin: 2.9%

b. I indicate in all non-metastatic patients which are candidates for cisplatin: 67.6%

c. I indicate only in selected cases (≥T3 or T2 with vascular invasion) and candidates for cisplatin: 29.4%

d. I do not routinely indicate and I refer for adjuvant chemotherapy after surgery: 0%

e. Abstention

12. Regarding the use of adjuvant chemotherapy in the treatment of muscle-invasive urothelial carcinoma: a. I indicate in all patients with staging> pT2N0, independent of cisplatin eligibility: 5.9%

b. I indicate in all patients with staging> pT2N0 that are eligible for cisplatin: 70.6%

c. I indicate only in cases pN+, regardless of cisplatin eligibility: 5.9%

d. I indicate only in cases pN+ and candidates for cisplatin: 14.7%

e. I do not indicate because there is no significant benefit: 2.9%

f. Abstention

12bis. Regarding the use of adjuvant chemotherapy in the treatment of muscle-invasive urothelial carcinoma: a. I indicate in all patients with staging> pT2N0, independent of cisplatin eligibility: 3.1%

b. I indicate in all patients with staging> pT2N0 that are eligible for cisplatin: 90.6%

c. I indicate only in cases pN+, regardless of cisplatin eligibility: 0%

d. I indicate only in cases pN+ and candidates for cisplatin: 3.1%

e. I do not indicate because there is no significant benefit: 3.1%

f. Abstention

13. Do you recommend neoadjuvant chemotherapy in patients who will undergo bladder preservation therapy? a. Yes: 29.4%

b. No: 47.1%

c. In selected cases: 23.5%

d. Abstention

13bis. Do you recommend neoadjuvant chemotherapy in patients who will undergo bladder preservation therapy? a. Yes: 0%

b. No: 97.3%

c. In selected cases: 2.7%

d. Abstention

14. Do you recommend neoadjuvant chemotherapy in patients who are not candidates for cisplatin? a. Yes: 8.8%

b. No: 64.7%

c. In selected cases: 26.5%

d. Abstention

14bis. Do you recommend neoadjuvant chemotherapy in patients who are not candidates for cisplatin? a. Yes: 6.5%

b. No: 90.3%

c. In selected cases: 3.2%

d. Abstention

15. When you recommend neoadjuvant chemotherapy in patients who are candidates for cisplatin, you recommend:

a. M-VAC: 11.1%

b. Dose dense M-VAC: 55.6%

c. Gemcitabine and cisplatin: 29.6%

d. Paclitaxel, gemcitabine and cisplatin: 3.7%

e. Other: 0%

f. I do not recommend chemotherapy in this scenario: 0%

g. Abstention

15bis. When you recommend neoadjuvant chemotherapy in patients who are candidates for cisplatin, you recommend:

a. M-VAC: 0%

b. Dose dense M-VAC: 62.5%

c. Gemcitabine and cisplatin: 33.3%

d. Paclitaxel, gemcitabine and cisplatin: 4.2%

e. Other: 0%

f. I do not recommend chemotherapy in this scenario: 0%

g. Abstention

16. Which chemotherapy regimen do you recommend in preservation therapy in patients candidates for cisplatin?

a. Cisplatin: 79.2%

b. 5FU + Mitomycin C: 16.7%

c. Gemcitabine in low dose: 0%

d. Carboplatin: 0%

e. Carboplatin and Paclitaxel: 4.2%

f. Others: 0%

g. Abstention

17. Which chemotherapy regimen do you recommend in preservation therapy in patients who are not candidates for cisplatin? a. 5FU + Mitomycin C: 37.5%

b. Gemcitabine in low dose: 41.7%

c. Carboplatin: 12.5%

d. Carboplatin and Paclitaxel: 4.2%

e. Others: 4.2%

f. Abstention

17bis. Which chemotherapy regimen do you recommend in preservation therapy in patients who are not candidates for cisplatin? a. 5FU + Mitomycin C: 4.8%

b. Gemcitabine in low dose: 85.7%

c. Carboplatin: 9.5%

d. Carboplatin and Paclitaxel: 0%

e. Others: 0%

f. Abstention

18. In patients with localized / locally advanced urothelial bladder carcinoma, who received neoadjuvant chemotherapy with a cisplatin-based regimen and presented unsatisfactory pathologic response, I recommend: a. Follow-up: 91.7%

b. Adjuvant chemotherapy with the same regimen used in neoadjuvant: 0%

c. Adjuvant chemotherapy with a different regimen from neoadjuvant, based on cisplatin: 4.2%

d. Adjuvant chemotherapy with different scheme from neoadjuvant, without platinum: 4.2%

e. Abstention

19. In patients with localized / locally advanced bladder urothelial carcinoma (pT3-4, pN+), eligible for cisplatin who did not receive neoadjuvant chemotherapy, I recommend adjuvant chemotherapy with: a. M-VAC: 0%

b. Dose dense M-VAC: 32%

c. Gemcitabine and cisplatin: 56%

d. Gemcitabine and cisplatin dose dense: 0%

e. Paclitaxel, gemcitabine and cisplatin: 12%

f. Other: 0%

g. Abstention

19bis. In patients with localized / locally advanced bladder urothelial carcinoma (pT3-4, pN+), eligible for cisplatin who did not receive neoadjuvant chemotherapy, I recommend adjuvant chemotherapy with: a. M-VAC: 0%

b. Dose dense M-VAC: 28%

c. Gemcitabine and cisplatin: 60%

d. Gemcitabine and cisplatin dose dense: 4.0%

e. Paclitaxel, gemcitabine and cisplatin: 8.0%

f. Other: 0%

g. Abstention

20. In patients with localized / locally advanced urothelial bladder carcinoma (pT3-4, pN+) ineligible for cisplatin who have not received neoadjuvant chemotherapy, I recommend adjuvant chemotherapy with: a. Carboplatin and Gemcitabine: 85.7%

b. Carboplatin, Paclitaxel, Gemcitabine: 7.1%

c. Carboplatin, Methotrexate and Vinblastine: 0%

d. Immunotherapy with Pembrolizumab or Atezolizumab: 7.1%

e. Gemcitabine, Paclitaxel and Adriamycin: 0%

f. Other: 0%

g. Abstention

21. In patients with locally advanced urothelial upper tract carcinoma, when I recommend perioperative treatment, I indicate: a. Neoadjuvant chemotherapy: 45.2%

b. Adjuvant chemotherapy: 51.6%

c. Adjuvant radiotherapy: 0%

d. I never indicate peri-operative therapy in upper tract tumors: 3.2%

e. Abstention

21bis. In patients with locally advanced urothelial upper tract carcinoma, when I recommend perioperative treatment, I indicate: a. Neoadjuvant chemotherapy: 32.1%

b. Adjuvant chemotherapy: 67.9%

c. Adjuvant radiotherapy: 0%

d. I never indicate peri-operative therapy in upper tract tumors: 0%

e. Abstention

22. Do you recommend neoadjuvant chemotherapy in patients with upper tract tumors not candidate for cisplatin? a. Yes: 8.8%

b. No: 64.7%

c. In selected cases: 26.5%

d. Abstention

22bis. Do you recommend neoadjuvant chemotherapy in patients with upper tract tumors not candidate for cisplatin? a. Yes: 7.1%

b. No: 89.3%

c. In selected cases: 3.6%

d. Abstention

23. In patients with urothelial upper tract carcinoma, eligible for cisplatin that I indicate neoadjuvant chemotherapy, I recommend: a. M-VAC: 4.3%

b. Dose dense M-VAC: 39.1%

c. Gemcitabine and cisplatin: 47.8%

d. Gemcitabine and cisplatin dose dense: 4.3%

e. Paclitaxel, gemcitabine and cisplatin: 4.3%

f. Other: 0%

g. Abstention

23bis. In patients with urothelial upper tract carcinoma, eligible for cisplatin that I indicate neoadjuvant chemotherapy, I recommend: a. M-VAC: 5.9%

b. M-VAC dose dense: 41.2%

c. Gemcitabine and cisplatin: 52.9%

d. Gemcitabine and cisplatin dose dense: 0%

e. Paclitaxel, gemcitabine and cisplatin: 0%

f. Other: 0%

g. Abstention

24. Do you recommend adjuvant chemotherapy in patients with upper tract tumors not eligible for cisplatin?

a. Yes: 69.6%

b. No: 21.7%

c. In selected cases: 8.7%

d. Abstention

24bis. Do you recommend adjuvant chemotherapy in patients with upper tract tumors not eligible for cisplatin?

a. Yes: 78.9%

b. No: 21.1%

c. In selected cases: 0%

d. Abstention

25. In patients with upper tract urothelial carcinoma eligible for cisplatin, who I indicate adjuvant chemotherapy, I recommend: a. M-VAC: 4.0%

b. Dose dense M-VAC: 16%

c. Gemcitabine and cisplatin: 76%

d. Gemcitabine and cisplatin dose dense: 4.0%

e. Paclitaxel, gemcitabine and cisplatin: 0%

f. Other: 0%

g. Abstention

26. In patients with upper tract urothelial carcinoma, who I indicate adjuvant chemotherapy and are not candidates for cisplatin, I recommend:

a. Carboplatin and Gemcitabine: 100%

b. Carboplatin, Paclitaxel, Gemcitabine: 0%

c. Carboplatin, Methotrexate and Vinblastine: 0%

d. Gemcitabine, Paclitaxel and Adriamycin: 0%

e. Immunotherapy with Pembrolizumab or Atezolizumab; 0%

f. Gemcitabine, Paclitaxel and Adriamycin: 0%

g. Other: 0%

h. Abstention

TREATMENT OF METASTATIC DISEASE

First-line treatment

27. Which treatment option is the most recommended for patients with metastatic urothelial carcinoma in first-line, fit for cisplatin? a. Cisplatin + Gemcitabine: 64%

b. Cisplatin + Gemcitabine + Paclitaxel: 4%

c. DD M-VAC: 24%

d. M-VAC: 4%

e. Cisplatin: 4%

f. Abstention

27bis. Which treatment option is most recommended for patients with metastatic urothelial carcinoma in first-line, fit for cisplatin? a. Cisplatin + Gemcitabine: 87.5%

b. Cisplatin + Gemcitabine + Paclitaxel: 0%

c. DD M-VAC: 12.5%

d. M-VAC: 0%

e. Cisplatin: 0%

f. Abstention

28. Which is the most recommended treatment option for patients with metastatic urothelial carcinoma in first-line, unfit for cisplatin, without FGFR mutations and no PD-L1 analysis? a. Carboplatin + Gemcitabine: 85%

b. M-CAVI: 0%

c. Gemcitabine + Paclitaxel: 0%

d. Paclitaxel + Gemcitabine + Carboplatin: 0%

e. Gemcitabine + Oxaliplatin: 0%

f. Gemcitabine + paclitaxel + adriamycin: 0%

g. Immunotherapy: 15%

h. Other: 0%

i. Abstention

29. Immunotherapy may be indicated in first-line in patients unfit for cisplatin: a. For all patients: 7.4%

b. Only when PD-L1 expression > 5% (Ventana-sp142) or greater than 10% (Dako-22C3), depending on the kit used: 44.4%

c. Patients not candidates for chemotherapy: 3.7%

d. Answers B and C: 40.7%

e. Never: 3.7%

f. Abstention

29bis. Immunotherapy may be indicated in first line in patients unfit for cisplatin: a. For all patients: 4.5%

b. Only when PD-L1 expression > 5% (Ventana-sp142) or greater than 10% (Dako-22C3), depending on the kit used: 13.6%

c. Patients not candidates for chemotherapy: 4.5%

d. Answers B and C: 77.3%

e. Never: 0%

f. Abstention

30. Which is the most recommended treatment option for patients with metastatic urothelial carcinoma in first-line, unfit for cisplatin, without FGFR mutations and PD-L1 negative (less than 5% or 10% in the recommended tests): a. Carboplatin + Gemcitabine: 87%

b. M-CAVI: 0%

c. Gemcitabine + Paclitaxel: 0%

d. Paclitaxel + Gemcitabine + Carboplatin: 0%

e. Gemcitabine + Oxaliplatin: 0%

f. Gemcitabine + paclitaxel + adriamycin: 0%

g. Immunotherapy: 4.3%

h. Other: 8.7%

i. Abstention

31. Which is the most recommended treatment option for patients with metastatic urothelial carcinoma in first-line, unfit for cisplatin, without FGFR mutations and PD-L1 positive (greater than 5% or 10% in the recommended tests): a. Carboplatin + Gemcitabine: 19%

b. M-CAVI: 0%

c. Gemcitabine + Paclitaxel: 0%

d. Paclitaxel + Gemcitabine + Carboplatin: 0%

e. Gemcitabine + Oxaliplatin: 0%

f. Gemcitabine + paclitaxel + adriamycin: 0%

g. Immunotherapy: 81%

h. Other: 0%

i. Abstention

32. When immunotherapy is recommended in first-line for unfit patients for cisplatin, which one do you prefer? a. Pembrolizumab: 28.6%

b. Atezolizumab: 0%

c. Pembrolizumab or Atezolizumab: 61.9%

d. Any anti-PD1 / PD-L1 agent: 9.5%

e. Abstention

32bis. When immunotherapy is recommended in first line for unfit patients for cisplatin, which one do you prefer? a. Pembrolizumab: 31.6%

b. Atezolizumab: 5.3%

c. Pembrolizumab or Atezolizumab: 63.2%

d. Any anti-PD1 / PD-L1 agent: 0%

e. Abstention

33. Which is the most recommended treatment option for patients with metastatic urothelial carcinoma in first-line, unfit for cisplatin, with FGFR mutations and PD-L1 negative (less than 5% or 10% in the recommended tests): a. Carboplatin + Gemcitabine: 81%

b. M-CAVI: 0%

c. Gemcitabine + Paclitaxel: 0%

d. Paclitaxel + Gemcitabine + Carboplatin: 0%

e. Gemcitabine + Oxaliplatin: 0%

f. Gemcitabine + paclitaxel + adriamycin: 0%

g. Immunotherapy: 19%

h. Other: 0%

i. Abstention

34. Which is the most recommended treatment option for patients with metastatic urothelial carcinoma in first line, unfit for cisplatin, with FGFR mutations and PD-L1 positive (greater than 5% or 10% in the recommended tests):

a. Carboplatin + Gemcitabine: 42.9%

b. M-CAVI: 0%

c. Gemcitabine + Paclitaxel: 0%

d. Paclitaxel + Gemcitabine + Carboplatin: 0%

e. Gemcitabine + Oxaliplatin: 0%

f. Gemcitabine + paclitaxel + adriamycin: 0%

g. Immunotherapy: 57.1%

h. Other: 0%

i. Abstention

34bis. Which is the most recommended treatment option for patients with metastatic urothelial carcinoma in first line, unfit for cisplatin, with FGFR mutations and PD-L1 positive (greater than 5% or 10% in the recommended tests):

a. Carboplatin + Gemcitabine: 87.5%

b. M-CAVI: 0%

c. Gemcitabine + Paclitaxel: 0%

d. Paclitaxel + Gemcitabine + Carboplatin: 0%

e. Gemcitabine + Oxaliplatin: 0%

f. Gemcitabine + paclitaxel + adriamycin: 0%

g. Immunotherapy: 12.5%

h. Other: 0%

i. Abstention

TREATMENT OF METASTATIC DISEASE Second-line treatment

35. The preferential treatment indicated for patients with disease progression following platinum-based chemotherapy, without FGFR mutation is:

a. Vinflunine: 4.8%

b. Gemcitabine: 4.8%

c. Docetaxel / Paclitaxel: 4.8%

d. Immunotherapy: 85.7%

e. Erdafitinib: 0%

f. Abstention

36. The preferential treatment indicated for patients with disease progression following platinum-based chemotherapy, with FGFR mutation is: a. Vinflunine: 0%

b. Gemcitabine: 0%

c. Docetaxel / Paclitaxel: 0%

d. Immunotherapy: 36.8%

e. Erdafitinib: 63.2%

f. Abstention

36bis. The preferential treatment indicated for patients with disease progression following platinum-based chemotherapy, with FGFR mutation is: a. Vinflunine: 0%

b. Gemcitabine: 5.3%

c. Docetaxel / Paclitaxel: 0%

d. Immunotherapy: 63.2%

e. Erdafitinib: 31.6%

f. Abstention

37. Immunotherapy may be indicated for patients with disease progression following platinum-based chemotherapy: a. For all patients: 81.8%

b. Only when there is expression of PD-L1> 5% or greater than 10%, depending on the kit used: 18.2%

c. Never: 0%

d. Abstention

38. Preferred immunotherapy for patients with disease progression following platinum-based chemotherapy: a. Pembrolizumab: 72.7%

b. Nivolumabe: 4.5%

c. Atezolizumab: 0%

d. Durvalumab: 0%

e. Any anti-PD1 / PD-L1 agent: 22.7%

f. Abstention

38bis. Preferred immunotherapy for patients with disease progression following platinum-based chemotherapy: a. Pembrolizumab: 95.5%

b. Nivolumabe: 0%

c. Atezolizumab: 0%

d. Durvalumab: 0%

e. Any anti-PD1 / PD-L1 agent: 4.5%

f. Abstention

39. The preferred treatment indicated for patients with disease progression following platinum-based chemotherapy and immunotherapy, without FGFR mutation is: a. Vinflunine: 45%

b. Gemcitabine: 5%

c. Docetaxel / Paclitaxel: 35%

d. Ifosfamide: 5%

e. Pemetrexate: 5%

f. Erdafitinib: 0%

g. Other 5%

h. Clinical Support Therapy: 0%

i. Abstention

39bis. The preferred treatment indicated for patients with disease progression following platinum-based chemotherapy and immunotherapy, without FGFR mutation is: a. Vinflunine: 66.7%

b. Gemcitabine: 0%

c. Docetaxel / Paclitaxel: 26.7%

d. Ifosfamide: 0%

e. Pemetrexate: 0%

f. Edarfitinib: 0%

g. Other: 0%

h. Clinical Support Therapy: 6.7%

i. Abstention

40. The preferred treatment indicated for patients with disease progression following platinum-based chemotherapy and immunotherapy, with FGFR mutation is: a. Vinflunine: 0%

b. Gemcitabine: 0%

c. Docetaxel / Paclitaxel: 0%

d. Ifosfamide: 0%

e. Pemetrexate: 0%

f. Erdafitinib: 95.8%

g. Other: 0%

h. Clinical Support Therapy: 4.2%

i. Abstention

BONE THERAPY

41. For urothelial carcinoma patients with bone metastases, you recommend therapy with bone modifying

agents (zoledronic acid, denosumab): a. For all patients: 54.5%

b. For most patients: 36.4%

c. Only in selected cases: 9.1%

d. There is no indication: 0%

e. Abstention

41bis. For urothelial carcinoma patients with bone metastases, you recommend therapy with bone modifying

agents (zoledronic acid, denosumab): a. For all patients: 63.2%

b. For most patients: 36.8%

c. Only in selected cases: 0%

d. There is no indication: 0%

e. Abstention

42. Among the bone modifying agents available, you have a preference for:

a. Zoledronic acid: 19.2%

b. Denosumab: 69.2%

c. No preference: 11.5%

d. Abstention

42bis. Among the bone modifying agents available, you have a preference for:

a. Zoledronic acid: 10.5%

b. Denosumab: 89.5%

c. No preference: 0%

d. Abstention

43. For patients taking zoledronic acid, the dose and frequency that you recommend are: a. 4mg IV every 4 weeks: 50%

b. 4mg IV every 12 weeks: 50%

c. Abstention

43bis. For patients taking zoledronic acid, the dose and frequency that you recommend are: a. 4mg IV every 4 weeks: 95%

b. 4mg IV every 12 weeks: 5%

c. Abstention

44. For patients taking desonumab, the dose and frequency you recommend are:

a. 120mg SC every 4 weeks: 82.6%

b. 120mg SC every 12 weeks: 17.4%

c. Abstention

45. For urothelial carcinoma patients with bone metastases, which duration of therapy do you recommend with bone modifying agents? a. No duration predeterminate or until a significant /intolerable adverse

event: 66.7%

b. Until 24 months: 20.8%

c. Until a new bone event: 12.5%

d. Abstention

45bis. For urothelial carcinoma patients with bone metastases, which duration of therapy do you recommend with bone modifying agents? a. No duration predeterminate or until a significant /intolerable adverse event:

42.1%

b. Until 24 months: 57.9%

c. Until a new bone event: 0%

d. Abstention

46. For urothelial carcinoma patients with bone metastases and under therapy with bone modifying agents that have a bone event, you recommend: a. Suspend the bone modifying agent indefinitely: 4.5%

b. Treat the bony event and proceed with the bone modifying agent: 95.5%

c. Abstention

47. For patients on treatment with bone modifying agents, you recommend calcium / vitamin D supplementation: a. For all patients: 75%

b. For most patients: 16.7%

c. Only in selected cases: 8.3%

d. There is no indication: 0%

e. Abstention

48. For patients who have a history of dental disturbance (tooth extraction, periodontal disease or extraction, dental implants), you recommend the use of bone modifying agents:

a. For all patients: 0%

b. Only after dental evaluation/treatment: 100%

c. We do not recommend: 0%

d. Abstention

49. For patients who, during therapy with bone modifying agents, presented osteonecrosis of the jaw, and in which this picture is solved, you recommend: a. Continue with the treatment at the usual dose: 12%

b. Continue with the treatment with lower dose: 12%

c. Continue with the treatment with less frequency: 16%

d. I do not recommend to continue treatment: 60%

e. Abstention

49bis. For patients who, during therapy with bone modifying agents, presented osteonecrosis of the jaw, and in which this picture is solved, you recommend: a. Continue with the treatment at the usual dose 5.0%

b. Continue with the treatment with lower dose: 0%

c. Continue with the treatment with less frequency: 0%

d. I do not recommend to continue treatment 95%

e. Abstention

50. For urothelial carcinoma patients with bone metastases that have decreased renal function, you recommend: a. Zoledronic acid (with corrected dose): 4.8%

b. Denosumab: 95.2%

c. No preference: 0%

d. I do not recommend in these cases: 0%

e. Abstention

GENETIC COUNSELING

51. For urothelial carcinoma patients with no risk factors history and less than 50 years of age, genetic counseling is recommended: a. For all patients: 14.3%

b. For most patients: 14.3%

c. Only in selected cases: 50%

d. We do not recommended: 21.4%

e. Abstention

51bis. For urothelial carcinoma patients with no risk factors history and less than 50 years of age, genetic counseling is recommended: a. For all patients: 0%

b. For most patients: 8.3%

c. Only in selected cases: 87.5%

d. We do not recommended: 4.2%

e. Abstention

52. For patients with urothelial carcinoma and personal or family history of endometrial and/or gastrointestinal tract polyps, genetic counseling is recommended: a. For all patients: 69.7%

b. For most patients: 24.2%

c. Only in selected cases: 6.1%

d. We do not recommended: 0%

e. Abstention

52bis. For patients with urothelial carcinoma and personal or family history of endometrial and/or gastrointestinal tract polyps, genetic counseling is recommended: a. For all patients: 0%

b. For most patients: 71.4%

c. Only in selected cases: 23.8%

d. We do not recommended: 4.8%

e. Abstention

53. For patients with urothelial carcinoma and personal or family history of endometrial cancer (especially endometrioid subtype) and/or colorectal cancer (especially mucinous subtype), genetic counseling is recommended: a. For all patients: 91.2%

b. For most patients: 5.9%

c. Only in selected cases: 2.9%

d. We do not recommended: 0%

e. Abstention

54. For patients with urothelial carcinoma and diagnosis of Lynch Syndrome, genetic counseling is recommended for patients and their families: a. For all patients: 97.1%

b. For most patients: 2.9%

c. Only in selected cases: 0%

d. We do not recommended: 0%

e. Abstention