Upper Urinary Tract Urothelial Cell Carcinoma

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2020

Upper urinary tract urothelial carcinoma 2020

 

Summary of changes

The literature for the complete document has been assessed and updated, whenever relevant. Conclusions and recommendations have been rephrased and added to throughout the current document.

Key changes for the 2020 print:

  • Section 3.1 – Epidemiology – has been expanded, resulting changes in Figure 3.1 and the addition of two new recommendations

 

3.4 Summary of evidence and recommendations for epidemiology, aetiology and pathology

 

Summary of evidence LE
Aristolochic acid and smoking exposure increases the risk for UTUC. 2
Patients with Lynch syndrome are at risk for UTUC. 3

 

Recommendations Strength rating
Evaluate patient and family history based on the Amsterdam criteria to identify patients with upper tract urothelial carcinoma. Weak
Evaluate patient exposure to smoking and aristolochic acid. Weak

 

  • Chapter 6 – Prognosis – additional information has been added, resulting in changes to Figure 6.1 and an additional recommendation.

 

6.7 Summary of evidence and guidelines for prognosis

 

Summary of evidence LE
Chronological age should not preclude radical nephroureterectomy with curative intent, where indicated. 3
Important prognostic factors include hydronephrosis, tumour multifocality, size, stage, grade, lymph node metastasis, lymphovascular invasion and variant histology. 3

 

Recommendations Strength rating
Use pre-operative factors to risk-stratify patients for therapeutic guidance. Weak

 

  • Chapter 7 – Disease management, has been restructured, including new information on adjuvant and neoadjuvant therapies. Both Figures 7.1 and 7.2 have been adapted and a number of new recommendations have been added.

 

7.1.6 Summary of evidence and guidelines for management of high-risk non-metastatic UTUC

 

Summary of evidence LE
Failure to completely remove the bladder cuff increases the risk of bladder cancer recurrence. 3
Lymphadenectomy improves survival in muscle-invasive UTUC. 3
Peri-operative chemotherapy may improve survival. 3
Single post-operative intravesical instillation of chemotherapy lowers the bladder cancer recurrence rate. 1

 

Recommendations Strength rating
Perform radical nephroureterectomy (RNU) in patients with high-risk non-metastatic upper tract urothelial carcinoma (UTUC). Strong
Perform open RNU in non-organ-confined UTUC. Weak
Remove the bladder cuff in its entirety. Strong
Perform a template-based lymphadenectomy in patients with muscle-invasive UTUC. Strong
Offer peri-operative chemotherapy to patients with muscle-invasive UTUC. Weak
Deliver a post-operative bladder instillation of chemotherapy to lower the intravesical recurrence rate. Strong

 

  • Section 7.2 – Metastatic disease has been expanded to include the latest information on immunotherapy, both in a first- and second-line setting, resulting in a new summary table.

 

7.2.4 Summary of evidence and guidelines for the treatment of metastatic UTUC

 

Summary of evidence LE
Radical nephroureterectomy may improve quality of life and oncologic outcomes in select metastatic patients. 3
Cisplatin-based combination chemotherapy can improve median survival. 2
Single-agent and carboplatin-based combination chemotherapy are less effective than cisplatin-based combination chemotherapy in terms of complete response and survival. 3
Non-platinum combination chemotherapy has not been tested against standard chemotherapy in patients who are fit or unfit for cisplatin combination chemotherapy. 4
PD-1 inhibitor pembrolizumab has been approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase III trial. 1b
PD-L1 inhibitor atezolizumab has been FDA approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase II trial. 2a
PD-1 inhibitor nivolumab has been approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase II trial. 2a
PD-1 inhibitor pembrolizumab has been approved for patients with advanced or metastatic UC ineligible for cisplatin-based first-line chemotherapy based on the results of a phase II trial but use of pembrolizumab is restricted to PD-L1 positive patients. 2a
PD-L1 inhibitor atezolizumab has been approved for patients with advanced or metastatic UC ineligible for cisplatin-based first-line chemotherapy based on the results of a phase II trial but use of atezolizumab is restricted to PD-L1 positive patients. 2a

 

Recommendations Strength rating
Offer radical nephroureterectomy as a palliative treatment to symptomatic patients with resectable locally advanced tumours. Weak
First-line treatment for cisplatin-eligible patients
Use cisplatin-containing combination chemotherapy with GC, MVAC, preferably with G-CSF, HD-MVAC with G-CSF or PCG. Strong
Do not offer carboplatin and non-platinum combination chemotherapy. Strong
First-line treatment in patients unfit for cisplatin
Offer checkpoint inhibitors pembrolizumab or atezolizumab depending on PDL-1 status. Weak
Offer carboplatin combination chemotherapy if PD-L1 is negative. Strong
Second-line treatment
Offer checkpoint inhibitor (pembrolizumab) to patients with disease progression during or after platinum-based combination chemotherapy for metastatic disease. Strong
Offer checkpoint inhibitor (atezolizumab) to patients with disease progression during or after platinum-based combination chemotherapy for metastatic disease. Weak
Only offer vinflunine to patients for metastatic disease as second-line treatment if immunotherapy or combination chemotherapy is not feasible. Alternatively, offer vinflunine as third- or subsequent-treatment line. Weak

GC = gemcitabine plus cisplatin; G-CSF = granulocyte colony-stimulating factor; HD-MVAC = high-dose methotrexate, vinblastine, adriamycin plus cisplatin; PD-L1 = programmed death ligand 1; PCG = paclitaxel, cisplatin, gemcitabine.

 

2019

The literature for the complete document has been assessed and updated, whenever relevant. Conclusions and recommendations have been rephrased and added to throughout the current document.

Key changes for the 2019 print:

  • Section 3.2 – Risk factors, has been expanded
  • Section 4.4 – Future developments, was added
  • Section 5.6 – Summary of evidence and guidelines for the diagnosis of urothelial carcinoma of the upper urinary tract – two  recommendations were added.

 5.6 Summary of evidence and guidelines for the diagnosis of urothelial carcinoma of the upper urinary tract

 

Recommendations Strength rating
Use CT for staging the chest. Strong
If CT is contra-indicated, magnetic resonance imaging may be used for imaging the abdomen and pelvis. Strong

 

  •  
    • Section 7.2.2 – Metastasectomy, has been added
    • Section 7.2.3 – Systemic treatments, has been expanded to include immune checkpoint inhibitors.

     

 

2018

Key changes for the 2018 print:

  • Figure 6.2 – Risk stratification of upper urinary tract urothelial carcinoma, tumour size cut off for high-risk UTUC has been changed to > 2 cm;
  • Section 6.6 – Summary of evidence and guidelines for prognosis – recommendation ‘Use the America Society of Anesthesiologists score to assess cancer-specific survival’ – was taken out;
  • Section 7.1.4.3 – Summary of evidence and recommendations for radical nephroureterectomy.
Recommendations Strength rating
Perform radical nephroureterectomy in patients with high-risk tumours. Strong
Technical steps of radical nephroureterectomy:
Offer a post-operative bladder instillation of chemotherapy to lower the intravesical

recurrence rate.

Strong

 

 

  • Section 8.1: Summary of evidence and follow-up of UTUC

 

Recommendations Strength rating
After radical nephroureterectomy:
Low-risk tumours
Perform cystoscopy at three months. If negative, perform subsequent cystoscopy nine months later and then yearly, for five years. Weak

 

Perform computed tomography urography every year for five years. Weak
High-risk tumours
Perform cystoscopy and urinary cytology at three months. If negative, repeat subsequent cystoscopy and cytology every three months for a period of two years, and every six months thereafter until five years, and then yearly. Weak

 

Perform computed tomography urography every six months for two years, and then yearly. Weak

 

After kidney-sparing management:
Low-risk tumours
Perform cystoscopy and computed tomography urography at three and six months, and then yearly for five years. Weak

 

Perform ureteroscopy at three months. Weak
High-risk tumours
Perform cystoscopy, urinary cytology and computed tomography urography at three and six months, and then yearly. Weak

 

Perform ureteroscopy and urinary cytology in situ at three and six months. Weak

 

2017

New relevant references have been identified through a structured assessment of the literature and

incorporated in the various chapters of the 2017 Urothelial Carcinoma of the Upper Urinary Tract Guidelines.

 Key changes for the 2017 print:

New section 3.3.1.1 – Summary of evidence for Chapter 3 (Epidemiology, aetiology and pathology) has been added.

 3.3.1.1     Summary of evidence for histology and classification

Summary of evidence LE
A small proportion of upper tract urothelial carcinoma belong to the tumour spectrum of the hereditary non-polyposis colorectal cancer. 3

New section 5.3 – Summary of evidence section has been added to the Guidelines for the diagnosis of upper tract urothelial carcinoma.

 5.3           Summary of evidence and guidelines for the diagnosis of upper tract urothelial carcinoma

Summary of evidence LE
The diagnosis of urothelial carcinoma of the upper urinary depends on computed tomography urography. 2
Selective urinary cytology has high sensitivity in high-grade tumours including carcinoma in situ. 3

New section 7.1.2.4 – Summary of evidence section has been added to the Guidelines for radical nephroureterectomy. 

7.1.2.4     Summary of evidence and guidelines for radical nephroureterectomy

Summary of evidence LE
Radical nephroureterectomy is the standard in high-risk upper tract urothelial carcinoma, regardless of tumour location. 2
Open and laparoscopic approaches have equivalent efficacy and safety in T1–2/N0 upper tract urothelial carcinoma. 2

 

2016

All chapters of the 2016 Urothelial Carcinomas of the Upper Urinary Tract Guidelines have been updated, based on the 2015 version of the guideline.Conclusions and recommendations have been rephrased and added to, throughout the current document.

Key changes for the 2016 print:

Changed or new conclusions and recommendations can be found in sections:

  • Section 6.2 Molecular markers has been added as a new topic.
  • Section 6.4 Bladder recurrence has been added as a new topic.

New recommendations have been included in Chapter 6 – Prognosis

6.6 Summary of evidence and guidelines for prognosis

Summary of evidence LE
Age, sex and ethnicity are no longer considered as independent prognostic factors. 3
The primary recognised post-operative prognostic factors are tumour stage and grade, extranodal extension and lymphocascular invasion. 3 

 

Recommendation LE GR
Use MSI as an independent molecular prognostic marker to help detect germline mutations and hereditary cancers. 3  C
Use the American Society of Anesthesiologists (ASA) score to assess cancer-specific survival following surgery. 3 C

MSI = Microsatellite instability. 

  • In section 7.1.2.1 Laparoscopic radical nephrectomy, the findings of a systematic review (Oncological outcomes of laparoscopic/robotic radical nephroureterectomy versus open radical nephroureterectomy for UTUC) have been included.
  • Section 7.2.2 Systemic chemotherapy has been expanded.
  • A new algorithm – Figure 7.2 Surgical treatment according to location and risk status – has been included.

2015

The literature for the complete document has been assessed and updated, whenever relevant.

  • Key changes for the 2015 print:
    New algorithms have been included:
    Fig. 3.1: Selection of patients with UTUC for hereditary screening from first medical interview.
    Fig. 6.1: UTUC prognostic factors;
    Fig. 6.2: Risk stratification of UTUC (table presentation in the 2014 print version);
    Fig. 7.1: Proposed flowchart for the management of UTUC was amended.

In Table 7.1. Guidelines for kidney sparing management of low-risk UTUC, the open surgical approach options have been expanded, not resulting in a change in the grade of recommendation (GR).

Surgical open approach
Renal pelvis or calyces:
Partial pyelectomy or partial nephrectomy is seldom indicated.
C
Ureter – Mid & proximal:
Ureteroureterostomy is indicated for tumours that cannot be removed completely endoscopically.
C
Ureter – Distal:
Complete distal ureterectomy and neocystostomy are indicated for tumours in the distal ureter that cannot be removed completely endoscopically.
C

2013

Limited update to include the most recent data.

 

2011

– New topic