A novel tool to predict functional outcomes after robot-assisted radical prostatectomy and the value of additional surgery for incontinence.

OBJECTIVES: To develop and validate a model to predict 12-month continence status after robot-assisted radical prostatectomy (RARP) from preoperative and 3-month postoperative data; this model could help in informing patients on their individualised risk of urinary incontinence (UI) after RP in order to choose the best treatment option. PATIENTS AND METHODS: Data on 9421 patients in 25 Belgian centres were prospectively collected (2009-2016) in a compulsory regional database. The primary outcome was the prediction of continence status, using the International Consultation on Incontinence Urinary Incontinence Short Form (ICIQ-UI-SF) at 12-months after RARP. Linear regression shrinkage was used to assess the association between preoperative 3-month postoperative characteristics and 12-month continence status. This association was visualised using nomograms and an online tool. RESULTS: At 12 months, the mean (sd) score of the ICIQ-UI-SF questionnaire was 4.3 (4.7), threefold higher than the mean preoperative score of 1.4. For the preoperative model, high European Association of Urology risk classification for biochemical recurrence (estimate [Est.] 0.606, se 0.165), postoperative radiotherapy (Est. 1.563, se 0.641), lower preoperative European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core (EORCT QLQ-C30)/quality of life (QoL) score (Est. -0.011, se 0.003), higher preoperative ICIQ-UI-SF score (Est 0.214, se 0.018), and older age (Est. 0.058, se 0.009), were associated with a higher 12-month ICIQ-UI-SF score. For the 3-month model, higher preoperative ICIQ-UI-SF score (Est. 0.083, se 0.014), older age (Est. 0.024, se 0.007), lower 3-month EORCT QLQ-C30/QoL score (Est. -0.010, se 0.002) and higher 3-month ICIQ-UI-SF score (Est. 0.562, se 0.009) were associated with a higher 12-month ICIQ-UI-SF score. CONCLUSIONS: Our models set the stage for a more accurate counselling of patients. In particular, our preoperative model assesses the risk of UI according to preoperative and early postoperative variables. Our postoperative model can identify patients who most likely would not benefit from conservative treatment and should be counselled on continence surgery.

Penile cancer: potential target for immunotherapy?

PURPOSE: Penile cancer (PeCa) is a rare malignancy with a poor prognosis in advanced disease. There is still a limited understanding of the biological mediators that are important in the prognosis and therapy of the disease. This review aims to provide a summary of the immune micro-environment, molecular oncogenesis and the role of HPV in the disease applying to the potential of the use of immunotherapy. METHODS: Narrative, non-systematic review based on publications retrieved by PubMed and EMBASE search. RESULTS: The molecular mechanisms underlying penile carcinogenesis are complex, and human papillomavirus (HPV) infection is a well-characterized driver of penile cancer. Up to 50% of the penile carcinomas are HPV related. There is potential to improve prevention, treatment and follow-up strategies pertaining to the role of HPV in penile cancer. Immune response modifiers such as toll-like receptor agonists are being used in a topical fashion for penile intraepithelial neoplasia while immune checkpoint inhibitors are currently under clinical investigation for its application in penile cancer. CONCLUSIONS: The knowledge of prognosis-relevant biological pathways in penile cancer is expanding. HPV plays an important role in the carcinogenesis. This can lead to the identification of therapeutic targets which could significantly influence the prognosis of advanced penile cancer. Clinical trials are being conducted to pave the way for immune-modifying treatment modalities.

Risk factors and molecular characterization of penile cancer: impact on prognosis and potential targets for systemic therapy.

PURPOSE OF REVIEW: To provide a comprehensive summary of risk factors, molecular machinery as well as potential therapeutic targets with a particular focus on literature published in the last 2 years on prognosis and treatment of penile cancer (PeCa). RECENT FINDINGS: E2F, LAMC2, MAML2, ID1 and IGFBP2 proteins were demonstrated to play a critical role for aggressive tumor behavior and might predict poor survival in PeCa. PD-L1 axis was confirmed as a promising pathway to serve as a therapeutic target. A number of genetic alterations were illuminated. In clinical testing, pan-HER tyrosine kinase inhibitor dacomitinib provided promising results in chemo-naïve and EGFR monoantibody nimotuzumab in chemotherapy-failed PeCa patients. SUMMARY: Knowledge of prognosis-relevant altered molecular pathways in PeCa is expanding paving the way for identification of potential therapeutic targets. Multicenter clinical trials in the setting of centralized PeCa care are warranted to foster effective marker-based individualized treatment strategies.