Editorial Comment from Dr Borkowska to Recurrence and progression in patients with non‐muscle invasive bladder cancer: Prognostic models including multicolor fluorescence in situ hybridization molecular grading

Abstract

In this issue of the journal, Lodde et al. assess the usefulness of “molecular grading fluorescence in situ hybridization (mG-FISH)” in a prognostic model for recurrence and progression using patients with non-muscle invasive bladder cancer.1 These were selected to be tumors of intermediate risk (according to the European Association of Urology definition), and FISH was carried out using multicolor probes to the centromeres of chromosomes 3, 7, 17 and the 9p21 locus. The authors found subclassification by mg-FISH into low risk (a diploid chromosomal pattern or only loss of 9p16 locus or chromosome 3 aneuploidy) and high risk (aneuploidy of chromosomes 7or 17) enabled a slight increase in the accuracy of the prognostic models, when compared with those derived using clinicopathological variables, such as tumor stage, grade, multiplicity and size, the patient's sex and age, and whether the patient received intravesical chemotherapy after resection. The study is notable for several reasons. Although it is retrospective in design, the authors used the UroVysion test as a prognostic tool (rather than diagnostic) to supplement the histopathological details of the tumor. As the authors suggested, patients with low mG-FISH could have less intensive and shorter treatment follow ups, which might reduce treatment costs. The downside to a less intensive surveillance strategy is potential delayed recognition of disease progression (which occurred in 16% of this cohort). This test causes no extra problems to a patient, as it is carried out in the urine sediment cells. Unfortunately, the relatively frequent problem (approximately 20%) is the insufficient number of cells (“no cells”) in the urine sediment specimen, which makes both the UroVysion test and the mG-FISH assessment impossible.2 As the proposed mG-FISH is treated as a supplement to the histopathological assessment of the tumor, perhaps it could be better to use this technique in the same tissue; that is, in the tumor, if, of course, after the initial recognition, this test is not carried out separately in order to monitor the disease. The authors underline that the use of the European Organization for the Research and Treatment of Cancer calculator, recommended by the European Association of Urology, did not allow selecting from the tested group those patients who will have disease recurrence or progression. It is a frequently mentioned imperfection of this calculator.3 Additionally, the introduction of the histopathological subclassifications might not be completely useful, and requires a great deal of experience in assessing specimens under the microscope. Bladder cancer is a heterogeneous disease – both interpatient and intratumor heterogeneity is important here.4 Hence, there are difficulties in finding markers that would be useful in routine practice. It is possible that heterogeneity itself and the variety of genetic changes are the reason for false negative results of the UroVysion test, whereas the histopathological recognition is positive. Therefore, undoubtedly, the proposed study shows an interesting approach, yet it requires analysis on a bigger and, what I find even more important, on a histopathologically homogeneous group of patients, so that clear conclusions can be drawn (patients with grade G3 should not be tested in the intermediate risk group). A similar approach with slightly different criteria for low- and high-risk positive FISH is presented in the work of Matsuyam et al.5 They found that the percentage of 9p21 loss (>12%) was an independent prognostic factor for recurrence, and the sum of the non-modal copy number fraction of chromosomes 3, 7 and 17 (>16%) was a prognostic factor for disease progression. None declared.