Ureteroscopic management of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (hereditary nonpolyposis colorectal cancer syndrome)

Abstract

Objectives To report our experience with ureteroscopic laser ablation of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (LS), as defined by a documented germline mutation in the MSH‐2 gene. To increase awareness among urologists about UTUC in this unique patient population and refer to genetic counselling when appropriate. Patients and Methods Demographic, clinical and pathological data on 13 consecutive patients with UTUC and documented MSH‐2 mutation comprising 15 involved renal units were retrospectively collected. Ureteroscopic evaluations involved biopsy and laser treatment with combination holmium/neodymium yttrium aluminum garnet (YAG) lasers. Tumours were graded from 1 to 3 according to the 1973 World Health Organisation classification by a single pathologist evaluating cell block preparations. Results The mean patient age at initial presentation was 56.5 years, with six of 13 patients having metachronous bilateral UT disease. The mean follow‐up was 59 months with a mean number of surveillances of 12. Of 15 affected renal units, 10/15 (67%) of initial tumours involved the ureter with mean lesion size of 17.5 mm, while five of 15 (33%) involved the intrarenal collecting system with mean lesion size of 25 mm. Ureteroscopy cleared 13/15 (87%) lesions and four of those 13 (31%) needed staged procedures. Renal preservation rate was 14/15 (93%) with one nephroureterectomy and one segmental ureterectomy performed. One patient developed metastatic UTUC after 40 months surveillance. No patient presented with bladder tumours but seven of the 13 (54%) developed them within 10 months of the initial ureteroscopy. Conclusions Patients with LS who develop UTUC present at younger ages and appear to be more likely to have bilateral UT disease over their lifetimes vs sporadic UTUC patients. Ureteroscopic laser ablation offers a good renal preservation rate with reasonable cancer control in patients willing to undergo endoscopic surveillance. Development of new bladder tumours is common.

Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening

“…Therefore, low malignant potential might be characteristic of LS‐associated UUTC, as it is of LS‐associated colorectal cancer. Although we experienced no bilateral UUTCs, a recent retrospective study reported a potentially increased risk of bilaterality . It is important to detect LS‐associated UUTC early and to survey the development of metachronous UUTC on the contralateral side.…”

“…As this limitation makes our conclusions weak, thoughtful interpretation and consideration of our data is required. MLH1/PMS2 protein loss is often caused by the hypermethylation of the MLH1 promoter region in elderly patients with colorectal cancer, which was not known in LS‐associated UUTCs . In one case with dual MLH1/PMS2 protein loss, we could not carry out genetic testing or BRAFV600E mutational status testing to examine hypermethylation of the MLH1 promoter region .…”

“…Although we experienced no bilateral UUTCs, a recent retrospective study reported a potentially increased risk of bilaterality. 24 It is important to detect LS-associated UUTC early and to survey the development of metachronous UUTC on the contralateral side. Considering these clinicopathological characteristics of LS-associated UUTC, renal preservation involving ureteroscopic laser ablation might be a better option than nephroureterectomy.…”

Lynch Syndrome: A Primer for Urologists and Panel Recommendations

“…22 They also described the effectiveness of ureteroscopic laser ablative treatment in patients with LS who had UTUC. Although selection bias cannot be ruled out, the potential for bilaterality should be considered, therefore, encouraging kidney preservation when clinically feasible.…”

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“…Yamada et al [1] recently reported a similar case of metachronous upper tract TCC associated with hereditary nonpolyposis cancer (HNPCC) requiring radical surgery. Hubosky et al [2] reported that of 13 HNPCC patients treated for upper tract TCC, 6 had bilateral disease.…”