[NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY - MIGHT IT BE OFFERED SELECTIVELY?]

INTRODUCTION: Neoadjuvant cisplatin-based chemotherapy prior radical cystectomy is the standard of care in patients with a muscle invasive bladder cancer. It is intended to treat micro-metastases. However, most patients do not develop metastases even without chemotherapy and are receiving this treatment in vain. In this study, we looked for pre-operative risk factors for developing metastases that can triage the patients that really need neoadjuvant therapy. METHODS: From 1998 to 2018, 285 patients underwent radical cystectomy without neoadjuvant chemotherapy. During a median follow-up of 42.5 months, 99 patients (34%) developed recurrent disease after a median duration of 12 months. The study compared 10 different preoperative parameters of patients who developed or did not develop recurrence. RESULTS: An increased risk of metastases was found in older patients (39.8% in older than 69 years vs. 33.3% in younger patients, p=0.045), in patients with a high Charlson Comorbidity index (46.2% in 5 and above vs. 28.2% when lower than 4, p=0.003), and in patients with large tumor diameter (p=0.01). No difference was found in the other variables examined including: gender, primary versus secondary tumor, tumor stage, presence of histological variant, hydronephrosis, carcinoma in situ (CIS) or sarcomatoid differentiation. CONCLUSIONS: Older age, comorbidity, and large tumor diameter predict the risk of recurrence after radical cystectomy. However, overlap between the groups precludes the use of these parameters for clinical decisions. Therefore, neoadjuvant chemotherapy treatment should currently be offered to all candidates for radical cystectomy. Hopefully, future molecular markers will be able to predict the risk of metastases.

High frequency of bladder cancer after nephroureterectomy: justification for adjuvant intravesical treatment?

BACKGROUND: Bladder recurrence after nephroureterectomy (NU) is common. However, there is no acceptable policy of adjuvant intravesical treatment after NU. OBJECTIVE: To assess the rate of bladder recurrence following NU and to identify the high-risk subgroups that may become candidates for adjuvant intravesical therapy after NU. PATIENTS AND METHODS: Ninety-one patients (mean age 66.4 years) underwent NU. High-grade (HG) tumors were found in 63 patients and low-grade (LG) tumors in 28. Median follow-up was 72 months. The risk of bladder recurrence was assessed by uni- and multivariate analyses of patient and tumor characteristics. RESULTS: Bladder recurrence developed in 38 patients (41.8%) after a median period of 11 months. Among these, 25 patients with HG upper tract urothelial carcinoma (39.7%) and 13 patients with LG upper tract urothelial carcinoma (46.4%) developed recurrence. HG bladder recurrence developed in 24 patients (63.2%) and LG recurrence developed in 14 patients (36.8%). Stages pTa, pT1, pT2, or higher bladder recurrence developed in 26 (68.4%), 7 (18.4%), and 4 patients (10.5%), respectively, and pure pTis developed in 1 patient. On uni- and multivariate analyses, the risk of bladder recurrence was independent of any clinicopathologic characteristics. CONCLUSION: High rate and short time interval of bladder recurrence after NU were found, with no specific subgroup of patients with increased risk. These findings support prescribing adjuvant intravesical therapy to all patients after NU.

Novel insights on human NK cells' immunological modalities revealed by gene expression profiling.

As part of the innate immune system, human NK cells play a critical role early in the systemic host defense against pathogens and tumor cells. Recent studies suggest a more complex view of NK cell behavior, as different functions and tissue localizing capabilities seem to be preferentially assigned to distinct subpopulations of NK cells, CD56(dim)CD16(+) or CD56(bright)CD16(-). In this study, we used oligonucleotide microarrays to compare the expression profile of approximately 20,000 genes in three NK cell subpopulations: peripheral blood-derived CD56(dim)CD16(+), CD56(bright)CD16(-), and in vitro-activated CD16(+) NK cells. The differential expression of selected genes was verified by flow cytometry and functional assays. When comparing CD56(dim)CD16(+) and CD56(bright)CD16(-) subsets, a new heterogeneous molecular basis for the functional and developmental differences between these two subsets was revealed. Furthermore, systematic analysis of transcriptional changes in activated CD16(+) NK cells provided us with a better understanding of NK function in inflamed tissues. We highlight a number of genes that were overexpressed upon activation (e.g., OX40 ligand, CD86, Tim3, galectins, etc.), that enable these cells to directly cross-talk with other innate and adaptive immune effectors. The overexpressed genes assign novel intriguing immunomodulatory functions to activated NK cells, in addition to their potent cytotoxic abilities.