Upper Urinary Tract Urothelial Cell Carcinoma

8. FOLLOW UP

The aims for follow-up after treatment for UTUC are to comply with patient rehabilitation needs, to detect recurrent or new primary tumours within the urothelium, and to detect regional and/or distant metastases. Bladder recurrence is not considered a distant recurrence. Unfortunately, the heterogeneity of available studies on disease-recurrence in UTUC is significant, and recommendations on follow-up have a low level of evidence at best.

After previous RNU for low-risk tumours, bladder follow-up should adopt the NMIBC follow-up protocol for low-risk disease, a cystoscopy at three months post-operatively, a subsequent cystoscopy nine months later and yearly cystoscopies for five years [288]. Screening for metastases during follow-up is not mandatory. Due to the low risk of contralateral upper tract recurrence, routine imaging should be discussed on an individual basis [289].

When RNU has been performed for high-risk tumours, stringent follow-up is mandatory to detect metachronous bladder tumours (probability increases over time [290]), local recurrence, and distant metastases. The risk of bladder recurrence is higher in patients with previous history of bladder cancer compared to those without, indicating the need for more intensive cystoscopy follow-up [291]. The risk of bladder recurrences and other-site recurrences decreases significantly four years after RNU, suggesting that less vigorous annual cystoscopies and cross-sectional imaging including CT urographies thereafter may apply [291].

After kidney-sparing management for low-risk UTUC, and where no subsequent upstaging or upgrading occurred after the early second-look ureteroscopy after six to eight weeks [154] or was found in the resection specimen after segmental ureteric resection, cystoscopy and CT-urography should be carried out at three and six months, and then yearly for five years. The risk for bladder recurrences beyond five years is low after endoscopic treatment and segmental ureterectomy [292,293].

In patients treated with kidney-sparing for high-risk tumours, the indication (imperative vs. non-imperative) affects the surveillance regimen by the consequences of recurrent disease. Still, the ipsilateral UUT requires careful and long-term follow-up due to the high risk of disease recurrence [153,294,295] and progression following RNU, even beyond five years [296].

Surveillance regimens are based on CT urography, cystoscopy and urinary cytology [290,297]. There are, however, several unanswered questions related to the optimal follow-up of patients treated for both low-risk and high-risk UTUC, of which some are:

• The added value of new urinary markers compared to cytology in voided urine samples in high-risk patients [298].
• The effect of the Paris System on sensitivity and specificity of voided and selective urinary cytology during follow-up of UTUC in high-risk tumours [299].
• If adjuvant upper tract instillations have been administered after endourologic kidney-sparing management, will that allow for less vigorous follow-up?
• The role of ureteroscopies of the ipsilateral upper urinary tract during follow-up after endourologic kidney-sparing treatment vs. CT urography and voided urinary cytology.

Additionally, it is not known how patients with Lynch syndrome, without and with UTUC, should be screened or followed long-term given the inadequacy of surveillance based on urinalysis for nonvisible haematuria [300] and urine cytology [301], particularly in those individuals who are MSH2 mutation carriers [53] and those who already have developed a UTUC. Section 8.1 presents the summary of evidence and recommendations for follow-up of UTUC.

8.1. Summary of evidence and recommendations for the follow-up of UTUC

*The role of ureteroscopies of the ipsilateral upper urinary tract during follow-up after endourologic kidney-sparing treatment vs. CT urography and voided urinary cytology is unknown.