Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Survival Impact of Variant Histology Diagnosis in Upper Tract Urothelial Carcinoma.

PURPOSE: Little is known regarding the prognostic implications of variant histology in upper tract urothelial carcinoma (UTUC). We sought to evaluate the impact of variant histology UTUC on patient survival outcomes at our institution. MATERIALS AND METHODS: We identified 705 patients who underwent nephroureterectomy for UTUC at our institution between January 1995 and December 2018. We tested the association between variant histology and cancer-specific survival (CSS) and overall survival (OS) using separate multivariable Cox models after adjusting for pathological stage. RESULTS: Forty-seven patients (6.7%) had variant histology, with prevalence increasing over time (p=0.003). Other demographic and surgical characteristics were similar between variant histology and pure urothelial carcinoma groups. While patients with variant histology were more likely to receive neoadjuvant chemotherapy (38% vs 15%, p <0.001), they were also more likely to have a higher pathological T stage (p <0.001). Variant histology was associated with significantly worse CSS (HR: 2.14; 95% CI 1.33, 3.44; p=0.002) and OS (HR: 1.74; 95% CI 1.15, 2.63; p=0.008). After adjusting for pathological T stage, variant histology was not significantly associated with CSS (HR: 1.17; 95% CI 0.72, 1.89; p=0.5) or OS (HR: 1.20; 95% CI 0.79, 1.84; p=0.4). CONCLUSIONS: Variant histology UTUC is associated with advanced stage and poor survival, and could serve as a useful biomarker for high-risk disease when pathological stage is unknown. However, the inferior CSS and OS with variant histology can be explained by the higher tumor stage on nephroureterectomy. Thus, finding variant histology on surgical pathology does not provide additional prognostic information beyond stage.

Management of giant osteoma in the mandible associated with minor trauma: a case report.

BACKGROUND: Osteoma is a benign tumor of the bones, which can be classified as central or peripheral. The occurrence in the jawbones is uncommon, but when it occurs, there is a greater prevalence of the mandible. The etiology is still unknown, and the hypothesis of its development is debated. CASE PRESENTATION: A 35-year-old Caucasian man presenting a tumor lesion in the right jawbone that had been growing for 8 years sought medical service complaining of speaking impairment. According to the patient, the tumor appeared shortly after a minor trauma caused by tooth extraction. The diagnosis of the lesion was made through clinical, radiographic, and histological methods, and the surgical treatment was successful and satisfactory for the patient as well as the surgical team, despite a short follow-up. CONCLUSION: Etiopathogenesis of osteoma is not determined in the majority of cases. In the present report, it was possible to hypothesize the association between a minor trauma and the development of the tumor, reinforcing the reactive theory of tumor development. The uncommon location of the osteoma, as well the possibility of identifying the possible cause of the lesion, makes this case particularly interesting.

Focal therapy for primary and salvage prostate cancer treatment: a narrative review.

Despite innovations in surgical technology and advancements in radiation therapy, radical treatments for clinically localized prostate cancer are associated with significant patient morbidity, including both urinary and sexual dysfunction. This has created a vital need for therapies and management strategies that provide an acceptable degree of oncologic efficacy while mitigating these undesirable side effects. Successful developments in screening approaches and advances in prostate imaging have allowed clinicians to identify, localize, and more precisely target early cancers. This has afforded urologists with an important opportunity to develop and employ focal ablation techniques that selectively destroy tumors while preserving the remainder of the gland, thus avoiding detrimental treatment effects to surrounding sensitive structures. A lack of high-level evidence supporting such an approach had previously hindered widespread adoption of focal treatments, but there are now numerous published clinical trials which have sought to establish benchmarks for safety and efficacy. As the clinical evidence supporting a potential role in prostate cancer treatment begins to accumulate, there has been a growing acceptance of focal therapy in the urologic oncology community. In this narrative review article, we describe the techniques, advantages, and side effect profiles of the most commonly utilized focal ablative techniques and analyze published clinical trial data supporting their evolving role in the prostate cancer treatment paradigm.