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Introduction: A considerable number of individuals with prostate cancer (PCa) still harbor locally-advanced and metastatic disease. Although such men were initially not considered eligible for local treatment, the role of radical prostatectomy (RP) has been recently reassessed. Areas covered: This review analyses currently published evidences regarding new surgical approaches for clinically high-risk PCa individuals, as well as the role of cytoreductive surgery in the metastatic setting. The role of robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection will be evaluated with regards to perioperative, oncologic, as well as functional outcomes. Expert commentary: RARP is a feasible approach in PCa patients regardless of the presence of high-risk disease features and can achieve optimal short-term oncologic outcomes and acceptable short/intermediate-term functional outcomes, that are comparable to those reported for open RP. Extended pelvic lymph node dissection can be performed in this setting and should be recommended for all high-risk PCa patients. The overall rate of complications in contemporary men treated with RARP for high-risk disease is not negligible. Cytoreduction in the oligo-metastatic setting is feasible and relatively safe, although evidence is scarce to recommend its widespread adoption. In consequence, longer follow-up data and, ideally, randomized controlled trials are needed.

The identification of activating mutations in the tyrosine kinase domain of the EGF receptor (EGFR) predictive of response to tyrosine kinase inhibitors (TKIs) led to a therapeutic revolution in the treatment of patients with metastatic non-small-cell lung cancer (NSCLC). To date, eight randomized clinical trials have demonstrated that first-line treatment with TKIs in advanced NSCLC patients harboring activating EGFR mutations is associated with significant improvement in response rate, progression-free survival, quality of life and tolerability, compared with platinum-based chemotherapy. These results prompted the EGFR TKIs as the current standard first-line treatment of patients with advanced NSCLC harboring activating EGFR mutations. However, there are several questions that need to be addressed, including the best choice among different EGFR TKIs, the treatment of resistant disease and of patients with specific clinical conditions. Ongoing and future, well-designed trials should answer all these questions.

The skin is the largest nonreproductive target tissue on which estrogen plays many beneficial and protective roles. Although neither exogenous hormones nor pregnancy represent significant risk factors for melanoma, epidemiological data suggest a higher survival rate in women with metastatic disease versus men and in premenopausal versus postmenopausal patients. Despite the fact that hyperestrogenic signaling has long been implicated in the initiation and progression of several tumors, the role of estrogens in malignant melanoma is still unclear. The cellular effects of estrogens are mediated by two subtypes of estrogen receptors (ERs). Estrogen receptor β (ERβ), the predominant ER in the skin, antagonizes the proliferative action mediated by estrogen receptor αα. According to recent immunohistochemical studies, ERβ protein expression decreases progressively with increased Breslow thickness and results in more invasive melanomas; thus, ERβ immunophenotype may distinguish melanomas linked to poor prognosis from those with a favorable course and lead to melanoma unresponsiveness to both estrogen and anti-estrogen treatment. Therefore, if future large-scale immunohistochemical and molecular studies point towards ERβ as an important factor in malignant melanoma progression, they will open up novel and targeted prognostic and therapeutic perspectives. © 2011 Expert Reviews Ltd.