MRI-guided focal laser ablation of prostate cancer: a prospective single-arm, single-center trial with 3 years of follow-up

PURPOSEWe aimed to assess post-interventional and 36-month follow-up results of a single-center, single-arm, in-bore phase I trial of focal laser ablation (FLA) guided by multiparametric magnetic resonance imaging (mpMRI).METHODSFLA procedures were done in-bore MRI using a transperineal approach. Primary endpoints were feasibility and safety expressed as lack of grade 3 complications. Secondary endpoints were changes in international prostate symptom score (IPSS), sexual health inventory for men (SHIM), quality of life (QoL) scores, and serum prostate specific antigen (PSA) levels. Treatment outcomes were assessed by combined mpMRI-ultrasound fusion-guided and extended sextant systematic biopsy after 12, 24, and optionally after 36 months.RESULTSFifteen participants were included. Seven patients (46.67%) had Gleason 3+3 and 8 patients (53.33%) had Gleason 3+4 cancer. All patients tolerated the procedure well, and no grade 3/4 complications occurred. All grade 1 and 2 complications were transient and resolved completely. There was no significant change in mean IPSS from baseline (-1, p = 0.460) and QoL (0, p = 0.441) scores following FLA but there was a significant drop in mean SHIM scores (-2, p = 0.010) compared to pretreatment baselines. Mean PSA significantly decreased after FLA (-2.5, p < 0.001). Seven out of 15 patients (46.67%) had residual cancer in, adjacent, or in close proximity to the treatment area (1 × 4+3=7, 1 × 3+4=7, and 5 × 3+3=6). Four out of 15 patients (26.67%) underwent salvage therapy (2 repeat FLA, 2 radical prostatectomy).CONCLUSIONAfter 3 years of follow-up we conclude focal laser ablation is safe and feasible without significant complications

Molecular biomarkers in the context of focal therapy for prostate cancer: Recommendations of a delphi consensus from the focal therapy society

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject

The role of multiparametric MRI in biopsy-naive prostate cancer

© 2019, US Government. Results of recent trials have shown the superiority of mpMRI to TRUS-guided systematic biopsy for detecting clinically significant prostate cancer. However, only performing an mpMRI risks missing MRI-invisible lesions and, therefore, there might be added value in performing both targeted and systematic biopsies in biopsy-naive patients

Adrenocortical Carcinoma: Current Therapeutic State-of-the-Art

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally conveys a poor prognosis. Currently, surgical resection is considered the lone curative treatment modality. In addition, the low prevalence of ACC has limited effective clinical trial design to develop evidence-based approaches to ACC therapy. The proper role of radio- and chemotherapy treatment for ACC is still being defined. Similarly, the molecular pathogenesis of ACC remains to be fully characterized. Despite these challenges, progress has been made in several areas. After years of refinement, an internationally accepted staging system has been defined. International collaborations have facilitated increasingly robust clinical trials, especially regarding agent choice and patient selection for chemotherapeutics. Genetic array data and molecular profiling have identified new potential targets for rational drug design as well as potential tumor markers and predictors of therapeutic response. However, these advances have not yet been translated into a large outcomes benefit for ACC patients. In this paper, we summarize established therapy for ACC and highlight recent findings in the field that are impacting clinical practice

Contemporary treatments in prostate cancer focal therapy

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose of reviewRadical treatments for prostate cancer are associated with significant morbidity, including incontinence and erectile dysfunction. Advances in the field of prostate MRI and desire to reduce treatment morbidities have led to a rapid growth in focal treatments for prostate cancer. Here, we review novel focal prostate cancer treatments and their associated recent clinical data, with a particular focus on data reported within the last 24 months.Recent findingsHigh-intensity focal ultrasound, focal laser ablation, irreversible electroporation, focal cryotherapy, and photodynamic therapy have been used as treatment modalities for localized prostate cancer treatment. Despite the great variety of treatment techniques, each of these modalities is characterized by a significant rate of prostate cancer persistence within treatment zones (6-50%) and the presence of residual cancer within the prostate on rebiopsy (24-49%). These treatments, however, are associated with very low rates of high-grade complications, rare incontinence, and only mild or transient reductions in erectile function. The most common adverse events are urinary tract infections, hematuria, and urinary retention.SummaryProstate cancer focal therapy is an attractive option for well-selected patients because of its low complication profile; however, long-term oncologic outcome is still lacking and early recurrence rates are high, limiting the ability of most urologic associations from endorsing its routine use

Immune therapy and β-cell death in type 1 diabetes.

Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing β-cells. The killing of β-cells is not currently measurable; β-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it is not known whether immune therapies affect killing. We developed an assay to identify β-cell death by measuring relative levels of unmethylated INS DNA in serum and used it to measure β-cell death in a clinical trial of teplizumab. We studied 43 patients with recent-onset T1D, 13 nondiabetic subjects, and 37 patients with T1D treated with FcR nonbinding anti-CD3 monoclonal antibody (teplizumab) or placebo. Patients with recent-onset T1D had higher rates of β-cell death versus nondiabetic control subjects, but patients with long-standing T1D had lower levels. When patients with recent-onset T1D were treated with teplizumab, β-cell function was preserved (P &lt; 0.05) and the rates of β-cell were reduced significantly (P &lt; 0.05). We conclude that there are higher rates of β-cell death in patients with recent-onset T1D compared with nondiabetic subjects. Improvement in C-peptide responses with immune intervention is associated with decreased β-cell death

Immune therapy and β-cell death in type 1 diabetes.

Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing β-cells. The killing of β-cells is not currently measurable; β-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it is not known whether immune therapies affect killing. We developed an assay to identify β-cell death by measuring relative levels of unmethylated INS DNA in serum and used it to measure β-cell death in a clinical trial of teplizumab. We studied 43 patients with recent-onset T1D, 13 nondiabetic subjects, and 37 patients with T1D treated with FcR nonbinding anti-CD3 monoclonal antibody (teplizumab) or placebo. Patients with recent-onset T1D had higher rates of β-cell death versus nondiabetic control subjects, but patients with long-standing T1D had lower levels. When patients with recent-onset T1D were treated with teplizumab, β-cell function was preserved (P &lt; 0.05) and the rates of β-cell were reduced significantly (P &lt; 0.05). We conclude that there are higher rates of β-cell death in patients with recent-onset T1D compared with nondiabetic subjects. Improvement in C-peptide responses with immune intervention is associated with decreased β-cell death