Dynamic prediction of metastases after radical prostatectomy for prostate cancer

Study Type – Prognosis (retrospective cohort) Level of Evidence 2a What’s known on the subject? and What does the study add? One of two problems plagues virtually are existing post‐prostatectomy prediction tools: either (1) they predict PSA recurrences (which are of unclear importance) or (2) the predictions they make are anchored at the date of surgery and are not updated based on how patients evolve over the postoperative years. Our prediction tool is a significant improvement over existing prediction tools in that it predicts the development of metastases which is a very important clinical endpoint that indicates incurable prostate cancer. Additionally, our tool allows for updated predictions at any point following radical prostatectomy by considering commonly available postoperative information (postoperative serum PSA and use of adjuvant therapies) to modify its risk predictions. The net result is a dynamic tool that renders clinically relevant predictions that change as the patient’s clinical status changes throughout the postoperative course.

OBJECTIVE

? To develop a dynamic algorithm that predicts the risk of metastases from any time point after radical prostatectomy (RP).

PATIENTS AND METHODS

? The study cohort consisted of 5741 RP patients who were treated from 1990–99. ? Patients were grouped into one of four clinical states at follow‐up: State₁, prostate‐specific antigen (PSA) undetectable; State₂, PSA 0.15–0.39 ng/mL; State₃, PSA ≥0.4 ng/mL; and State₄, previous androgen deprivation or radiation therapy. ? Follow‐up epochs (alive and at risk of systemic progression) at 0, 2, 4 and 6 years post‐RP, cumulative incidence curves and multistate Cox models were used to assess the risk of metastases over the ensuing 5‐year interval. ? Gleason score, seminal vesicle and surgical margin involvement, and PSA variables were evaluated as predictors.

RESULTS

? Median follow‐up was 11.7 years, with 4411, 4256 and 3983 patients followed with PSA at 2, 4 and 6 years, respectively. ? In total, 287 metastatic events occurred and the 5‐year risk of metastasis was 0.4%, 2.1%, 8.7% and 12.6% for men in States 1, 2, 3 and 4, respectively. ? Independent predictors of metastasis by group included seminal vesicle involvement (all groups), Gleason score (groups 1, 3 and 4), current PSA (groups 3 and 4) and maximum past PSA (group 4).

CONCLUSIONS

? We present a web‐based prognostic tool for patients undergoing RP that is valid at many time points after surgery. ? Our tool predicts the development of metastases.     

Back to the future: proceedings from the 2010 NF Conference

The neurofibromatoses (NF) encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect 100,000 Americans; over 2 million persons worldwide; and are caused by mutation of tumor suppressor genes. Individuals with NF1 in particular may develop tumors anywhere in the nervous system; additional manifestations can include learning disabilities, bone dysplasia, cardiovascular defects, unmanageable pain, and physical disfigurement. Ultimately, the NFs can cause blindness, deafness, severe morbidity, and increased mortality and NF1 includes a risk of malignant cancer. Today there is no treatment for the NFs (other than symptomatic); however, research efforts to understand these genetic conditions have made tremendous strides in the past few years. Progress is being made on all fronts, from discovery studies-understanding the molecular signaling deficits that cause the manifestations of NF-to the growth of preclinical drug screening initiatives and the emergence of a number of clinical trials. An important element in fuelling this progress is the sharing of knowledge, and to this end, for over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share ideas and build collaborations. The 2010 NF Conference held in Baltimore, MD June 5-8, 2010 hosted over 300 NF researchers and clinicians. This paper provides a synthesis of the highlights presented at the Conference and as such, is a "state-of-the-field" for NF research in 2010.     

SCFβ-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination

CYLD negatively regulates the NF-κB signaling pathway and osteoclast differentiation largely through antagonizing TNF receptor-associated factor (TRAF)-mediated K63-linkage polyubiquitination in osteoclast precursor cells. CYLD activity is controlled by IκB kinase (IKK), but the molecular mechanism(s) governing CYLD protein stability remains largely undefined. Here, we report that SCF^β-TRCP regulates the ubiquitination and degradation of CYLD, a process dependent on prior phosphorylation of CYLD at Ser432/Ser436 by IKK. Furthermore, depletion of β-TRCP induced CYLD accumulation and TRAF6 deubiquitination in osteoclast precursor cells, leading to suppression of RANKL-induced osteoclast differentiation. Therefore, these data pinpoint the IKK/β-TRCP/CYLD signaling pathway as an important modulator of osteoclastogenesis.     

Oncology education in Canadian undergraduate and postgraduate medical programs: a survey of educators and learners

Background

The oncology education framework currently in use in Canadian medical training programs is unknown, and the needs of learners have not been fully assessed to determine whether they are adequately prepared to manage patients with cancer.

Methods

To assess the oncology education framework currently in use at Canadian medical schools and residency training programs for family (fm) and internal medicine (im), and to evaluate opinions about the content and utility of standard oncology education objectives, a Web survey was designed and sent to educators and learners. The survey recipients included undergraduate medical education curriculum committee members (umeccms), directors of fm and im programs, oncologists, medical students, and fm and im residents.

Results

Survey responses were received from 677 educators and learners. Oncology education was felt to be inadequate in their respective programs by 58% of umeccms, 57% of fm program directors, and 50% of im program directors. For learners, oncology education was thought to be inadequate by 67% of medical students, 86% of fm residents, and 63% of im residents. When comparing teaching of medical subspecialty–related diseases, all groups agreed that their trainees were least prepared to manage patients with cancer. A standard set of oncology objectives was thought to be possibly or definitely useful for undergraduate learners by 59% of respondents overall and by 61% of postgraduate learners.

Conclusions

Oncology education in Canadian undergraduate and postgraduate fm and im training programs are currently thought to be inadequate by a majority of educators and learners. Developing a standard set of oncology objectives might address the needs of learners.     

Peripheral Nerve Stimulation for the Treatment of Postamputation Pain—A Case Report

Many amputees suffer from postamputation pain, which can be extremely debilitating, decrease quality of life, increase the risk of depression, and negatively affect interpersonal relationships and the ability to work. Present methods of treatment, including medications, are often unsatisfactory in reducing postamputation pain. Electrical stimulation of the nerve innervating the painful area could reduce the pain, but peripheral nerve stimulation is rarely used to treat postamputation pain because present methods require invasive surgical access and precise placement of the leads in close proximity (≤ 2 mm) with the nerve. The present study investigated a novel approach to peripheral nerve stimulation in which a lead was placed percutaneously a remote distance (> 1 cm) away from the femoral nerve in a patient with severe residual limb pain (RLP) 33 years following a below‐knee amputation. Electrical stimulation generated ≥ 75% paresthesia coverage, reduced RLP by > 60%, and improved quality of life outcomes as measured by the pain interference scale of the Brief Pain Inventory‐Short Form (100% reduction in pain interference), Pain Disability Index (74% reduction in disability), and the Patient Global Impression of Change (very much improved) during a 2‐week home trial. There were no adverse events. The ability to generate significant paresthesia coverage and pain relief with a single lead inserted percutaneously and remotely from the target nerve holds promise for providing relief of postamputation pain.     

Poromatosis in pregnancy: a case of 8 eruptive poromas in the third trimester

The poroid family of neoplasms includes hidroacanthoma simplex, eccrine poroma, dermal duct tumor, and poroid hidradenoma. These benign adnexal neoplasms are derived from the eccrine or apocrine sweat ducts or glands. Poroid neoplasms, including poromas, have been reported during pregnancy and have been hypothesized to be hormonally influenced. Poromatosis, the occurrence of multiple poromas, rarely has been reported in association with hidrotic ectodermal dysplasia, prior radiation therapy, and non-Hodgkin lymphoma occurring after chemotherapy. We report a case of eruptive poromatosis in pregnancy with 8 poromas occurring in the third trimester, further supporting the hypothesis of a hormonal association in the etiology of this neoplasm.