2015 European guidelines for the diagnosis and treatment of upper urinary tract uroepithelial carcinoma Abstract Jiwei Huang, Department of Urology, Shanghai Renji Hospital
INTRODUCTION: Based on a systematic literature search, the EAU upper urinary tract uroepithelial carcinoma guideline working group has prepared a new version of the 2015 guideline; the guideline discusses the etiology and prognostic factors based on a systematic search of relevant literature in Medline, and gives the latest and standardized procedures for diagnosis, radical treatment and conservative treatment.
I. TMN staging
TMN staging remains an important consideration in the selection of treatment options and prediction of prognosis for UTUC.
The current guidelines still recommend using the 2009 TMN staging of the International Union Against Cancer
Primary tumor(T)
Tx
Primary tumor cannot be determined
T0
No evidence of primary tumor
Ta
Non-invasive papillary carcinoma
Tis
Carcinoma in situ
T1
Tumor infiltrates into subepithelial connective tissue
T2
Tumor invades the muscle layer
*T3
(renal pelvis) tumor infiltration beyond the muscular layer and infiltration of peripelvic fat or renal parenchyma
(Ureter) Tumor infiltrates beyond the muscular layer and infiltrates the fatty tissue around the ureter
T4
Tumor infiltrates adjacent organs or penetrates the kidney to infiltrate the perinephric fat
Regional lymph nodes(N)
Nx
Local lymph nodes cannot be identified
N0
No local lymph node metastasis
N1
Single lymph node metastasis, maximum diameter ≤ 50px
N2
Single lymph node metastasis with a maximum diameter of 2-125px, or multiple lymph node metastasis but with a maximum diameter of ≤125px
N3
Lymph node metastasis with maximum diameter >125px
Distant metastasis (M)
Mx
Distant metastasis cannot be determined
M0
No distant metastasis
M1
Distant metastasis
* It has been proposed to subdivide T3 (renal pelvis) into pT3a (microscopic renal parenchymal invasion) and pT3b (largely seen as renal parenchymal or perirenal fat invasion). pT3b patients have more aggressive tumors and are more prone to recurrence.
II. Diagnosis
Diagnostic methods recommended by the guidelines
Recommended grade
Urine cytology
A
Cystoscopy: exclude concomitant bladder cancer
A
Spiral CT urogram
A
Diagnostic ureteroscopy with biopsy C
Retrograde pyelogram C
* FISH (fluorescence in situ hybridization technique) has a limited role in the diagnosis of UTUC.
III. Prognostic influencing factors
1) Preoperative influencing factors.
Age, gender, race, smoking, tumor location (ureteral and multiple tumors have a worse prognosis than pelvic tumors), surgical preparation time (delay in surgical timing may increase the chance of disease progression), other (ASA classification, ECOG score, obesity, etc.)
2) Postoperative influencing factors.
TMN staging.
Lymph node involvement and choroidal lymphatic invasion.
Surgical margins.
Histopathology: extensive tumor necrosis (>10%); tumor morphology (non-tipped tumors have the worst prognosis); recurrence and mortality are higher in those with a history of organ-confined UTUC combined with carcinoma in situ or carcinoma in situ of the bladder.
3) Molecular markers
Studies have found that some cell adhesion molecules (E calcineurin and CD24), differentiation factors, etc. can be used as independent predictors of prognosis; however, there is no molecular marker whose effective performance has been widely proven to support its use as a reference standard for clinical decision-making.
IV. Treatment
1. Limited disease
1) Radical nephroureteral resection remains the gold standard for the treatment of high-risk UTUC; the area of lymph node dissection (LND) at the time of radical surgery has not been precisely defined anatomically; the area of lymph node dissection may have a greater impact on patient prognosis relative to the number, and regional lymph node dissection is currently recommended for patients with T2 and higher stages, and is not recommended for patients with UTUC at TaT1 stage LND is routinely performed; however, appropriate dissection can be performed according to the lymphatic return pathway: pelvic end: dissection of medial ureteral lymph nodes; dissection of retroperitoneal lymph nodes (right side: paraventricular, left side: parietal abdominal aorta) for high ureteral tumors/renal pelvis tumors
2) Conservative treatment.
2.1 Kidney-conserving surgery: For low-risk patients, conservative treatment can preserve renal function and avoid complications associated with open radical surgery. Conservative treatment is also recommended for some patients (renal insufficiency, isolated kidney), and can be selectively performed for low-stage, low-grade cases (normal contralateral renal function).
2.2 Ureteroscopy : Endoscopic laser ablation may be considered in some patients with high selectivity, but the patient should be informed of the close postoperative follow-up and that radical resection is still recommended.
2.3 Percutaneous treatment: The percutaneous route can be considered for low-risk patients located in the renal pelvis, mainly for low-grade tumors in the inferior calyces of the kidney that cannot be treated by ureteroscopy.
2.4 Partial ureterectomy: It is suitable for low-grade ureteral tumors in the middle and lower end or high-risk tumors that require protection of renal function.
2.5 Local adjuvant therapy: After conservative treatment of UTUC or in situ cancer surgery, local adjuvant therapy can be performed by special nephrostomy tube infusion of BCG or mitomycin C
Treatment of progressive tumors.
For progressive tumors, the clinical significance of performing radical surgery is still worth exploring. Systemic chemotherapy and radiotherapy can be applied in the clinic.
V. Follow-up program
Strict postoperative follow-up includes checking for the presence of bladder cancer, local recurrence or distant metastases.
The follow-up schedule is recommended.
At least 5 years of follow-up after radical total nephroureterectomy
Non-invasive tumors
Cystoscopy/urine cytology: at 3 months postoperatively and annually thereafter
CT urogram: once a year
Infiltrative tumors
Cystoscopy/urine cytology: 3 months post-operative and annually thereafter
CT uroscopy: 6 months for 2 years and annually thereafter
After conservative treatment surgery, at least 5 years of follow up
Urine cytology and spiral CT urography: at 3 months, 6 months and annually thereafter
Cystoscopy, ureteroscopy, cytology at the lesion: at 3 and 6 months postoperatively, once every 6 months for 2 years thereafter, and annually thereafter