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BACKGROUND: Patients with Bacillus Calmette–Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell–activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan–Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan–Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer–specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Purpose of Review: The identification of cell surface antigens is critical to the development of future prognostic and therapeutic modalities for the treatment of prostate cancer. Several prostate-specific proteins have been identified and are under investigation. This review reports on prostate stem cell antigen (PSCA), a protein with restricted expression that may have prognostic and therapeutic utility., Recent Findings: PSCA is a glycosylphosphatidylinositol-anchored cell-surface protein belonging to the Ly-6/Thy-1 family of cell surface antigens, and a murine homologue has been described. It is expressed in the normal human prostate and overexpressed in human prostate cancers. Its overexpression has been correlated with increased Gleason score, advanced stage and bone metastasis. PSCA is co-amplified with MYC, an independent predictor of progression and death. PSCA may therefore be a useful predictor of tumor biology and a useful target of immunotherapy against prostate cancer. Evidence suggests a potential role in strategies employing cytotoxic T cell lymphocytes. Anti-tumor activity has been demonstrated with monoclonal antibodies in tumor take and established tumor xenograft models. Conjugated antibody has recently been reported to have anti-tumor activity in preclinical models., Summary: PSCA may serve as a tool in refining the prognosis of an individual cancer and may be a useful therapeutic target for immunotherapy. Future studies will be required to confirm its clinical utility as a prognostic factor. Future animal and clinical studies will be required to test various immunotherapy strategies for safety and efficacy. The study of PSCA regulation and expression may provide information on normal prostate development and prostate carcinogenesis.

The authors do not have all of the data about enuresis, and many children are subject to relapses or failure of treatment. There is no cause for despondency, however. Enuresis is no longer a mystery. Good data exist about the natural history, epidemiology, and etiology of enuresis. In addition, multiple treatment modalities are available to practitioners. This article has sought to review the scientific literature and to relate the authors' experience with enuresis. The authors recommend a treatment program for children with monosymptomatic nocturnal enuresis that includes removal of caffeine from the diet. Enuretic children do not consume enough fluid, and the authors recommend that the daily fluid requirement be divided during the day: 40% in the morning, 40% in the afternoon, and 20% in the evening, with no restriction of fluid. Normalization of small functional bladder capacities may help to cure enuresis and has an effect on the efficacy of other therapies. Treatment of enuretics with antibiotics is effective in children with UTI, bacteriuria, or cystitis cystica. DDAVP has been shown to be effective in the treatment of enuresis, especially in children who have achieved a normal functional bladder capacity. Bladder alarm systems also offer a potential cure of enuresis, are inexpensive, and show a low relapse rate.