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No Survival Advantage for Palliative Gastrectomy
For some patients with advanced gastric cancer, palliative gastrectomy has been used to provide rapid symptomatic relief of pain, nausea, bleeding, obstruction, and perforation, as well as a possible survival benefit; studies involving palliative gastrectomy have not controlled for other factors that could influence survival such as systemic chemotherapy. The survival benefit of gastrectomy in patients treated with modern systemic chemotherapy was directly tested in the phase III REGATTA trial, in which 175 patients with advanced gastric cancer and a single non-curable factor confined to the liver, peritoneum, or paraaortic lymph nodes were randomly assigned to chemotherapy alone or chemotherapy preceded by gastrectomy. The trial was closed prematurely after an interim analysis suggested that the primary endpoint, overall survival, was not significantly improved by gastrectomy, and that patients undergoing gastrectomy had a significantly higher incidence of several serious adverse events related to chemotherapy. Routine palliative gastrectomy cannot be justified in these patients.
Hypofractionated Radiation Therapy for Localized Prostate Cancer
Conventional schedules for radiation therapy for localized prostate cancer use highly conformal techniques with a daily dose of 1.8 to 2.0 Gy for 38 to 45 fractions given over seven to eight weeks. Theoretical considerations based upon the biology of prostate cancer have suggested that higher dose fractions given over a shorter period of time might be equally effective. Preliminary results from three large randomized trials, two of which have only been presented as abstracts, provide data supporting the use of hypofractionated schedules with the potential to provide greater patient convenience. Final analysis of these trials will be required to support a definitive recommendation for hypofractionation.
Atezolizumab Immunotherapy for Platinum-Resistant Metastatic Urothelial Carcinoma
Platinum-based chemotherapy is the standard treatment for patients with metastatic urothelial carcinoma, but there is no standard approach once progressive disease has developed. In an expanded phase II study, atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody, demonstrated a 15 percent objective response rate in patients who had previously been treated with platinum-based chemotherapy; over 80 percent of responses were ongoing at 12 months. A phase III trial versus chemotherapy is ongoing to confirm these findings.
Atypical Glandular Cells on Cervical Cytology Associated With Immediate and Long-Term Risks of Cervical Cancer
Women with atypical glandular cells (AGC) on cervical cytology appear to be at increased risk for cervical cancer in both the short and long term. A recent study used data from Swedish national registries to analyze outcomes of over 14,000 women with AGC on their first recorded cervical cancer screening test. Immediately following an AGC result, adenocarcinoma was identified in 0.99 percent of women and squamous carcinoma in 0.30 percent. Compared with women with normal cytology at their first recorded cervical cancer screening test, women with AGC continued to be at higher risk of cervical cancer for up to 15.5 years. The highest risk of cervical cancer was in the first 3.5 years, and then decreased over time.
Immune-Related Responses With Checkpoint Inhibitors in Advanced Melanoma
The pattern of response to treatment with checkpoint inhibitors often differs from those with molecularly targeted agents or cytotoxic chemotherapy; patients may have a transient worsening of disease, manifested either by progression of known lesions or the appearance of new lesions, before disease stabilizes or tumor regresses. In a series of 592 patients with metastatic melanoma who were treated with pembrolizumab and had RECIST-defined progressive disease by 12 weeks, 14 percent eventually had disease stabilization or responded without a change to alternative therapy. Thus, patients who do not have symptoms should continue on therapy and have a confirmatory scan documenting progressive disease before being switched to an alternative treatment.