8. FOLLOW-UP
The objectives of 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, namely, a cystoscopy at three months postoperatively, a subsequent cystoscopy nine months later and yearly cystoscopies for five years [301]. 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 [302].
When RNU has been performed for high-risk tumours, stringent follow-up is mandatory to detect metachronous bladder tumours (probability increases over time [303]), local recurrence and distant metastases. The risk of bladder recurrence is higher in patients with a previous history of BC compared to those without, indicating the need for more intensive cystoscopy follow-up [304]. 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 may apply [304]. As for other non-urothelial recurrences after RNU, most lung metastases develop within two years of surgery [305], supporting a more intensive use of chest CT during this period.
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 [167], 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 [306,307].
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 upper urinary tract requires careful and long-term follow-up due to the high risk of disease recurrence [171,308,309] and progression following RNU, even beyond five years [310]. The risk of bladder recurrences is likely higher in patients with a previous history of BC prior to segmental ureterectomy [216,305].
Surveillance regimens are based on CT urography, cystoscopy and urinary cytology [303,311]. There are, however, several unanswered questions related to the optimal follow-up of patients treated for both low-risk and high-risk UTUC, some of which are:
- What is the added value of new urinary markers compared to cytology in voided urine samples in high-risk patients [115]?
- What is 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 [312]?
- If adjuvant upper tract instillations have been administered after endourologic kidney-sparing management, will that allow for less vigorous follow-up?
- What is the role of ureteroscopies of the ipsilateral upper urinary tract during follow-up after endourologic kidney-sparing treatment versus CT urography and voided urinary cytology?
Additionally, it is not known how patients with Lynch syndrome, with and without UTUC, should be screened or followed long-term, given the inadequacy of surveillance based on urinalysis for non-visible haematuria [313] and urine cytology [314], particularly in those individuals who are MSH2 mutation carriers [315] and those who have already developed 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 upper urinary tract urothelial carcinoma
| Summary of evidence | LE |
| Follow-up should be based on risk stratification and the type of treatment. | 3 |
| Recommendations | Strength rating |
| After radical nephroureterectomy (RNU) | |
| Low-risk tumours | |
| Perform cystoscopy at three months. If negative, perform subsequent cystoscopy nine months later and then yearly for five years. | Weak |
| High-risk tumours | |
| In patients with a prior history of non-muscle-invasive bladder cancer (NMIBC), perform cystoscopy and voided 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 |
| In patients without a prior history of NMIBC, perform cystoscopy and voided urinary cytology at three months. If negative, repeat subsequent cystoscopy and cytology every six months for a period of two years and every year thereafter until five years. | Weak |
| Perform computed tomography (CT) urography and chest CT every six months for two years, and then yearly. | Weak |
| After kidney-sparing management | |
| Low-risk tumours | |
| For bladder follow-up, perform cystoscopy at three and six months and then yearly for five years. | Weak |
| For upper tract follow-up, after negative second-look ureteroscopy (URS), perform CT urography at three and six months and then yearly for five years with or without URS*. | Weak |
| High-risk tumours | |
| In patients with a prior history of NMIBC, perform cystoscopy and voided urine cytology at three months. If negative, repeat subsequent cystoscopy and cytology every three months for two years, then every six months for five years, and then yearly. | Weak |
| In patients without a prior history of NMIBC, perform cystoscopy and voided urine cytology at three months. If negative, repeat subsequent cystoscopy and cytology every six months for two years, then every year for five years (same follow-up schedule as for high-risk tumours after RNU). | Weak |
| For upper tract follow-up, after negative second-look URS, perform cross-sectional imaging urography and URS at three and six months and then CT urography every six months for two years and then every year for five years, with or without URS*. | Weak |
*The role of URS of the ipsilateral upper urinary tract during follow-up after endourologic kidney-sparing treatment versus CT urography and voided urinary cytology is unknown.