Bisphosphonates in oncology: evidence for the prevention of skeletal events in patients with bone metastases

Bone metastases frequently occur in patients with advanced solid tumors, particularly breast and prostate cancers, and nearly all patients with multiple myeloma have some degree of skeletal involvement. The strides made in treating these primary tumors have extended median survival times and thereby increased patient risk for skeletal-related events (SREs), including pathologic fractures, spinal cord compression, need for palliative radiation therapy or surgery to bone, and hypercalcemia. Bisphosphonates, inhibitors of osteoclastic bone resorption that were first established as treatment of osteoporosis, have been shown to prevent and/or delay SREs related to malignancy. The results of a large, randomized phase 3 study comparing zoledronic acid and pamidronate in breast cancer or multiple myeloma patients with osteolytic lesions showed that the incidence of SREs, time to first SRE, and risk of developing a SRE were similar between treatment groups. However, in patients with solid tumors (excluding breast or prostate cancer) metastatic to the bone, only zoledronic acid has demonstrated clinical efficacy. Although bone turnover marker levels, such as N-telopeptide of type I collagen, have been shown to correlate with clinical response, additional studies are needed to validate their ability to predict response to bisphosphonate therapy

Recent advances in focal therapy of prostate and kidney cancer

The concept of focal therapy in oncologic surgery refers to maximizing healthy tissue preservation while maintaining excellent cancer control outcomes. Herein, we address the recent advantages in the field of focal therapy for both kidney and prostate cancer, focusing on technological achievements and future perspectives

Defining the Incremental Utility of Prostate Multiparametric Magnetic Resonance Imaging at Standard and Specialized Read in Predicting Extracapsular Extension of Prostate Cancer

AbstractMultiparametric magnetic resonance imaging (mpMRI) is increasingly used in staging early prostate cancer (PCa) but remains heavily reader-dependent. We aim to define the incremental utility of mpMRI over clinical parameters in determining the pathologic extracapsular extension (pECE) of PCa interpreted in a standard radiologic setting and when further over-read by a specialized reader. We retrospectively reviewed 120 men with clinically localized PCa undergoing mpMRI and radical prostatectomy. We obtained radiologic prediction of pECE from standard radiologic reports (standard read) and by a specialized reader blinded to clinical and pathologic findings (specialized read). We determined the incremental benefit of standard read and specialized read by sequential addition to a baseline clinical parameters-only logistic regression model predicting pECE. The sensitivity and specificity of standard read were 77% and 44%, respectively, whereas those of specialized read were 86% and 81%. The positive likelihood ratio was 1.7 at baseline, 1.7 adding standard read, and 6.5 adding specialized read. The negative likelihood ratio was 0.6 at baseline, 0.5 adding standard read, and 0.1 adding specialized read. Standard read modestly improved prediction of pECE, whereas specialized read improved it moderately.Patient summaryThe incremental benefit of mpMRI over clinical information is small but increases to moderate with a specialized second opinion. This second opinion may be useful when considering active surveillance, nerve-sparing surgery, or focal therapy

Focal therapy for prostate cancer: Evolutionary parallels to breast cancer treatment. Letter.

To the Editor:We read with great interest the recentmanuscript by Labbate et al reviewing the develop-ment of focal therapy in breast and prostate cancer(PCa).1Breast focal therapy (bFT) represents a suc-cessful model for organ-sparing cancer treatment, soas urologists sensible to prostate focal therapy (pFT)we can learn much about the complex process of bFTrecognition by the scientific community

Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer

Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NF?B) and vascular endothelial growth factor (VEGF). We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NF?B, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30?g/day) for ?30 days. Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively. After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (?=0.677, P<.0001), enterolactone (?=0.676, P<.0001), and enterodiol (?=0.628, P<.0001). Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (?=?0.217, P=.011, and ?=?0.230, P=.007, respectively), and a near-significant inverse association was observed for enterodiol (?=?0.159, P=.064). An inverse association was observed between enterolactone and VEGF (?=?0.143, P=.141), although this did not reach statistical significance. We did not observe an association between enterolignans and NF?B. In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140111/1/jmf.2012.0159.pd

Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer

BackgroundThe time between the diagnosis of cancer and a planned definitive surgical procedure offers a strong and direct approach for assessing the impact of interventions (including lifestyle interventions) on the biology of the target tissue and the tumor. Despite the many strengths of presurgical models, there are practical issues and challenges that arise when using this approach.Purpose/MethodsWe recently completed an NIH-funded phase II trial that utilized a presurgical model in testing the comparative effects of flaxseed supplementation and/or dietary fat restriction on the biology and biomarkers associated with prostatic carcinoma. Herein, we report the rationale for our original design, discuss modifications in strategy, and relay experiences in implementing this trial related to the following topics: (1) subject accrual; (2) subject retention; (3) intervention delivery; and (4) retrieval and completion rates regarding the collection of paraffin-embedded and fresh frozen prostate tissue, blood, urine, ejaculate, anthropometric measures and survey data.ResultsThis trial achieved its accrual target, i.e., a racially-representative (70% white, 30% minority) sample of 161 participants, low rates of attrition (7%); and collection rates that exceeded 90% for almost all biospecimens and survey data. While the experience gained from pilot studies was invaluable in designing this trial, the complexity introduced by the collection of several biospecimens, inclusion of a team of pathologists (to provide validated readings), and shifts in practice patterns related to prostatectomy, made it necessary to revise our protocol; lessons from our experiences are offered within this article.ConclusionsWhile our experience specifically relates to the implementation of a presurgical model-based trial in prostate cancer aimed at testing flaxseed-supplemented and fat-restricted diets, many of the lessons learned have broad application to trials that utilize a presurgical model or dietary modification within various cancer populations

Clinical, Pathologic, and Functional Outcomes After Nephron-Sparing Surgery in Patients with a Solitary Kidney: A Multicenter Experience

Abstract Background and Purpose: Surgical management of a renal neoplasm in a solitary kidney is a balance between oncologic control and preservation of renal function. We analyzed patients with a renal mass in a solitary kidney undergoing nephron-sparing procedures to determine perioperative, oncologic, and renal functional outcomes. Patients and Methods: A multicenter study was performed from 12 institutions. All patients with a functional or anatomic solitary kidney who underwent nephron-sparing surgery for one or more renal masses were included. Tumor size, complications, and recurrence rates were recorded. Renal function was assessed with serum creatinine level and estimated glomerular filtration rate. Results: Ninety-eight patients underwent 105 ablations, and 100 patients underwent partial nephrectomy (PN). Preoperative estimated glomerular filtration rate (eGFR) was similar between the groups. Tumors managed with PN were significantly larger than those managed with ablation (P<0.001). Ablations were associated with a lower overall complication rate (9.5% vs 24%, P=0.01) and higher local recurrence rate (6.7% vs 3%, P=0.04). Eighty-four patients had a preoperative eGFR ≥60?mL/min/1.73?m2. Among these patients, 19 (23%) fell below this threshold after 3 months and 15 (18%) at 12 months. Postoperatively, there was no significant difference in eGFR between the groups. Conclusions: Extirpation and ablation are both reasonable options for treatment. Ablation is more minimally invasive, albeit with higher recurrence rates compared with PN. Postoperative renal function is similar in both groups and is not affected by surgical approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98449/1/end%2E2012%2E0114.pd

The role of focal therapy in the management of localised prostate cancer: a systematic review

CONTEXT: The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy. OBJECTIVE: To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy. EVIDENCE ACQUISITION: Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included. EVIDENCE SYNTHESIS: A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2-100%, 29-40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting. CONCLUSIONS: Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required