Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. MethodsAn expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. ResultsConsensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. ConclusionTo our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease. J Clin Oncol 36:414-424. © 2017 by American Society of Clinical Oncology INTRODUCTIONProstate cancer (PCA) is the third leading cause of cancer-related death in US men, accounting for 26,730 deaths in 2017. 1 There is increasing evidence that PCA has substantial inherited predisposition, 2,3 with higher risks conferred by BRCA2 and BRCA1 (associated with hereditary breast and ovarian cancer [HBOC] syndrome), and HOXB13 (associated with hereditary prostate cancer [HPC]). Furthermore, BRCA2 mutations have been associated with poor PCA-specific outcomes. [9][10][11][12][13] There is also emerging evidence of the link between PCA Author affiliations and support information (if applicable) appear at the end of this article.Published at jco.org on December 13, 2017. and DNA mismatch repair (MMR) gene mutations (accounting for Lynch syndrome [LS]). [25][26][27][28][29][30] Furthermore, inherited genetic mutations are being uncovered in up to 12% of men with metastatic PCA, primarily in DNA repair genes such as BRCA1, BRCA2, and ATM, 31,32 with improved clinical outcomes by specific targeted agents. 33,34 Identifying genetic mutations of inherited PCA, therefore, has implications for cancer...

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.

Background Accelerated (also termed dose-dense, DD) chemotherapy regimens such as accelerated methotrexate, vinblastine, doxorubicin, and cisplatin have shown better efficacy and tolerability in the metastatic setting, and shortened the time to surgery in the neoadjuvant setting compared to standard-schedule regimens. We hypothesized that a DD schedule of gemcitabine and cisplatin (GC) would shorten the time to surgery and yield similar pathologic complete response rates (pT0) in patients with muscle-invasive bladder cancer (MIBC) compared with historical controls with standard GC. Objective To determine the safety and efficacy of neoadjuvant DDGC in MIBC. Design, setting, and participants Patients with cT2–4a, N0–1, M0 MIBC were eligible and received three 14-d cycles of DDGC with pegfilgrastim support followed by radical cystectomy with lymph node dissection. The primary end point was the pT0 rate. Molecular subtypes were assigned and correlated with survival. Results and limitations Thirty-one patients were evaluable for toxicity and response, of whom 58% had baseline clinical stage >T2N0M0; the median age was 69 yr. Ten patients (32%, 95% confidence interval [CI] 16–49%) achieved ypT0N0 status at cystectomy. Another four patients (13%, 95% CI 1–25%) were downstaged to non–muscle-invasive (

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