Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art.

Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal-papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.

Restaging transurethral resection in ta high-grade nonmuscle invasive bladder cancer: a systematic review.

PURPOSE OF REVIEW: The role of a re-transurethral resection (TUR) is clearly demonstrated in T1 high-grade nonmuscle invasive bladder cancer. However, its role remains controversial for Ta high-risk tumors and the recent European guidelines stated that the second look procedure could be avoided for these patients despite harboring a high-risk of both disease recurrence and progression. We aimed to evaluate the added benefit on staging, response to bacillus Calmette-Guérin and oncological outcomes of re-TUR in patients with Ta high-grade nonmuscle invasive bladder cancer. RECENT FINDINGS: Overall, we identified 15 studies, including 3912 patients from which 743 harbored Ta high-grade disease. Delay between first and second TUR was ranging from 2 to 12 weeks (median 5.6 weeks). The rate of residual disease was 52.8% (range 17-67%). The rate of overall upstaging to T1 and muscle-invasive disease were 10.9 and 4.7%, respectively. Although there was a trend toward improvement of recurrence-free survival outcomes, no definitive conclusions can be drawn due to the retrospective design of the studies included. SUMMARY: Residual tumor is common after initial TUR for Ta high-grade. Re-TUR is useful in reducing the rates of residual disease, may improve staging, response to bacillus Calmette-Guérin and oncological outcomes.

Bladder recurrence after radical nephroureterectomy: predictors and impact on oncological outcomes.

OBJECTIVES: To identify predictive factors of bladder recurrence after radical nephroureterectomy and to evaluate the impact of this event on oncological outcomes. METHODS: We carried out a retrospective analysis of 237 patients treated with radical nephroureterectomy for urothelial carcinoma of the upper tract at our institution from 1998 to 2011. Univariable and multivariable models evaluated the prognostic factors of bladder recurrence, and its impact on recurrence-free survival and cancer-specific survival. RESULTS: The median age was 69.3 years (interquartile range 60-76). With a median follow up of 44 months (interquartile range 24-79), bladder recurrence occurred in 85 patients (35.9%). A previous history of bladder cancer (P = 0.01) and the presence of concomitant carcinoma in situ (P = 0.005) remained independent predictors of bladder recurrence. The presence of bladder recurrence was not correlated with worse oncological outcomes in terms of disease recurrence (P = 0.075) and cancer-specific mortality (P = 0.06). However, the patients who experienced muscle-invasive bladder cancer recurrence had worse outcomes in terms of cancer-specific mortality (P = 0.01). Standard pathological features of aggressiveness, such as higher tumor stage (P = 0.05), higher grade (P = 0.01) and carcinoma in situ (P = 0.03), were independent predictors of muscle-invasive bladder cancer recurrence. CONCLUSIONS: Previous history of bladder cancer, tumor location and concomitant carcinoma in situ are independent predictors of bladder recurrence in patients undergoing radical nephroureterectomy. Bladder recurrence overall does not impact the oncological outcomes, but a muscle-invasive bladder recurrence is associated with a worse cancer-specific mortality. Standard pathological features of urothelial carcinoma of the upper tract aggressiveness (pT-stage, grade) are independent predictors of muscle-invasive bladder cancer recurrence.

The high rate of de novo graft carcinomas in renal transplant recipients.

BACKGROUND: To investigate the incidence, the clinical characteristics and outcomes of renal graft carcinomas in the same renal transplant population. METHODS: From April 1989 to April 2012, 1,037 consecutive renal transplantations were performed in our department. Data were collected prospectively in an extensively maintained database. For all recipients, monitoring consisted of clinical examination and an abdominopelvic CT scan or ultrasonography at least once a year. RESULTS: After 1,037 renal transplantations, 48 men and 14 women (sex ratio 3:4) with a mean age of 54 years (25.1-78.9) were included for urological malignancies. Eight graft carcinomas were identified: 7 renal cell carcinomas (5 papillary carcinomas and 2 clear cell carcinomas of the renal graft) and 1 transitional cell carcinoma of the ureteral graft (incidence 0.78%). Nephron-sparing surgery was chosen for 5 patients with good outcomes. All graft renal cell carcinomas were classified as pT1a and the mean size of tumors was 28.4 mm (range 6-45). The 5-year specific survival rate was 100%. No recurrence was observed with a mean follow-up of 36.8 months (4.1-84.3). CONCLUSION: Thus confirming an increased risk of de novo graft cancer, close monitoring of renal transplant recipients should be discussed with at least an abdominopelvic ultrasonography and PSA measurement once a year. Renal cell graft carcinomas seemed to be mostly small and of papillary type and low grade.