Control computerized tomography in neoadjuvant chemotherapy for muscle invasive urinary bladder cancer has no value for treatment decisions and low correlation with nodal status.

BACKGROUND: Control computerized tomography (cCT) is routinely used in many cystectomy centres before the final treatment cycle in patients with muscle-invasive urinary bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC). This is for evaluating response or nonresponse to NAC treatment. In a real-world retrospective cohort, we intended to evaluate the frequency of changed individual treatment strategies following cCT and to investigate any discrepancies between cCT-results on nodal staging and final pN-stages. METHODS: We performed a retrospective data-based, multicenter study of 242 MIBC-patients, staged cT2N0M0-cT4aN0M0, having undergone NAC and radical cystectomy (RC) between 2008 and 2019 at four Swedish cystectomy centres. Statistical analysis was performed using IBM SPSS statistics 26. RESULTS: Overall, 139/242 patients were examined with cCT. Six patients were staged as progressive at cCT and 5/139 (3.6%) underwent a change of previously planned treatment strategy. 2/6 patients with suspected progression (33%) did not change strategy and underwent all preplanned NAC-cycles plus RC. Only 1/6 patients assigned as progressive at the cCT, showed progression in the postoperative pathology specimen. In total 133/139 patients were considered being without progress on cCT, yet 28/133 (21%) presented with nodal progression at postoperative pathology examinations. Only 1/29 patients with histopathologically verified nodal dissemination were detected with cCT, thus 28/29 (96.6%) with pN + were undetected. The sensitivity for cCT to predict pTNM was 17% CI [0%-64%] and the specificity was 78% CI [71%-86%]. CONCLUSIONS: CCT prior to the final treatment cycle of NAC in MIBC, leads to a low percentage of treatment strategy changes and cCT cannot accurately predict pN-status.

Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer.

Tissue-resident memory T (TRM ) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate TRM cell phenotypes. We discovered that tumour TRM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin-expressing TRM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour TRM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that TRM cells from tumours are not terminally exhausted. Moreover, a high number of TRM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, TRM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies TRM cells as potential new targets for cancer immunotherapy.