Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population.
Philip J. Saylor and Matthew R. Smith
Allan Lipton, Robert Uzzo, Robert J. Amato, Georgiana K. Ellis, Behrooz Hakimian, G. David Roodman and Matthew R. Smith
Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.
Julie R. Gralow, J. Sybil Biermann, Azeez Farooki, Monica N. Fornier, Robert F. Gagel, Rashmi N. Kumar, Charles L. Shapiro, Andrew Shields, Matthew R. Smith, Sandy Srinivas and Catherine H. Van Poznak
Bone health and maintenance of bone integrity are important components of comprehensive cancer care in both early and late stages of disease. Risk factors for osteoporosis are increased in patients with cancer, including women with chemotherapy-induced ovarian failure, those treated with aromatase inhibitors for breast cancer, men receiving androgen-deprivation therapy for prostate cancer, and patients undergoing glucocorticoid therapy. The skeleton is a common site of metastatic cancer recurrence, and skeletal-related events are the cause of significant morbidity. The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force on Bone Health in Cancer Care to discuss the progress made in identifying effective screening and therapeutic options for management of treatment-related bone loss; understanding the factors that result in bone metastases; managing skeletal metastases; and evolving strategies to reduce bone recurrences. This report summarizes presentations made at the meeting.
Doreen A. Ezeife, Sunil Parimi, Ellen R. Cusano, Matthew K. Smith, Tony H. Truong, Soundouss Raissouni, Yongtao Lin, Jose G. Monzon, Haocheng Li, Vincent C. Tam and Patricia A. Tang
Background: Phase III trials in metastatic colorectal cancer (mCRC) have collectively led to progressive advancements in patient outcomes over the past decades. This study characterizes the evolution of mCRC phase III trials through assessing the value of cancer therapy, as measured by the ASCO Value Framework. Methods: Phase III trial results of systemic therapy for mCRC published between 1980 and 2015 were identified, and their outcome, statistical significance, journal impact factor, and citation by the 2016 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CRC were recorded. For each trial, the net health benefit (NHB) score was calculated using the June 2015 (original) and May 2016 (revised) ASCO Value Framework: Advanced Disease. Results: There were 114 mCRC phase III trials eligible for calculation of the NHB score. Using the revised framework, the median NHB score was 4.6 (range, −30 to 43.5); 12% of trials received bonus points. Trials with statistically significant results had higher NHB scores compared with nonsignificant trials (median NHB score, 21.6 vs 2.9; P<.0001). Clinical trials cited in the NCCN Guidelines had higher NHB scores than those not cited (median score, 8.0 vs 0.3; P=.02). In multivariate linear regression analysis, the only significant predictor of high NHB score was statistically significant studies. Conclusions: The median NHB score for mCRC phase III trials was 4.6. Higher NHB scores are associated with statistically significant studies and are cited in the NCCN Guidelines, a surrogate for practice-changing trials. The 2016 ASCO Value Framework may not fully capture the benefits on an individual patient level.