Review Articles in 2007

Active surveillance for favorable-risk prostate cancer has become increasingly popular in populations in which prostate cancer screening is widespread because of evidence that screening results in the detection of disease that is not clinically significant in many patients. This Review discusses the results of active surveillance, the criteria for patient selection and the appropriate thresholds for intervention.

Primary tumor removal is usually considered as intrinsically beneficial, but this can perturb metastatic homeostasis and, for some patients, results in the acceleration of metastatic cancer. This Review analyzes the recent evolution of two paradigms related to the development of breast cancer metastases, and discusses the limitations of these paradigms in terms of how they explain breast cancer recurrence dynamics for patients undergoing surgery with or without adjuvant chemotherapy.

The pathogenic relationship between bisphosphonates and osteonecrosis of the jaw is unclear, but there is evidence to indicate an association between high-dose bisphosphonate treatment and exposure to dental infections and oral surgical procedures. The authors of this Review highlight that a better knowledge of the interactions between these agents and of the jaw and maxillary bone biology will improve clinical and therapeutic approaches to osteonecrosis of the jaw.

Techniques that combine the skills of resection with reconstruction have led to a third approach called oncoplastic breast-conserving reconstruction. Emerging data on the oncological and cosmetic outcomes of this technique confi rm the clinical utility of this new approach to the surgical management of patients with breast cancer, as discussed in this Review.

While many studies assessing the cost of cancer care have been conducted in the US, to date, these studies and the underlying methods used to estimate costs have not been reviewed systematically. The authors of this article conducted a descriptive review of the published literature on the cost of cancer care in the US, and discuss the implications of the heterogeneity of their findings.

The current choice for men with localized prostate cancer lies between active surveillance and radical therapy, but overtreatment associated with therapy poses a significant challenge. The authors of this Review propose a new concept whereby only the tumor focus and a margin of normal tissue are treated. The advantages and limitations of active surveillance and of radical therapy are reviewed, with focal therapy presented as a means for bridging these two approaches. With emerging techniques that can treat to millimeter accuracy, focal therapy of prostate cancer is now possible.

There is no standard treatment forBRCA1/2carriers with a new diagnosis of breast cancer. Personal and family-history-based criteria do not accurately predict the probability of a positive test result and thresholds for deciding who should be tested vary considerably among countries. The authors of this Review discuss how preventive and therapeutic approaches can be tailored to individuals by integrating the latest translational and clinical research findings. They also propose an individualized management algorithm on the basis of existing evidence, and discuss the challenges related to genetic testing, prevention and treatment strategies.

Population-based survival data can provide valuable comparative data on outcome but should be interpreted with caution. Ideally, data from the whole population, including clinical-only diagnoses, should be reported and the methods of case identification described. Erridge et al. highlight the need for methods of data collection and comparison to be as similar as possible, and for important factors related to the patient, tumor characteristics and treatment that might impact outcome to be reported.

The insulin-like growth factor 1 (IGF1) signaling pathway is implicated in the development of cancer. IGF1R signaling has been found to correlate with resistance to anti-EGFR and HER2-based therapies in experimental systems. This Review highlights the most relevant studies in this exciting area of research, focusing in particular on the role of the IGF1R in the resistance of other receptor-targeted therapies.

Despite recent advances in the field of medical and radiation oncology, and the introduction of neoadjuvant and adjuvant regimens, surgery remains the single most important modality for the treatment of pancreatic ductal adenocarcinoma. This Review discusses the technical improvements that have made pancreatic surgery safe, with low morbidity and mortality rates in tertiary referral centers, and it highlights the challenges of surgical palliation.

Emerging knowledge of the normal breast cell types has led to the hypothesis that the subtypes of breast cancer might arise from mutations or genetic rearrangements that occur in different populations of stem cells and progenitor cells. The authors of this Review describe the common distinguishing features of these breast cancer subtypes and explain how these relate both to prognosis and to selection of the most appropriate therapy.

The molecular mechanisms that underpin angiogenesis in breast cancer are becoming clearer, particularly in relation to hypoxia. Some established therapies including tamoxifen and trastuzumab might function, in part, by suppressing angiogenesis. The authors of this Review discuss the potential of components of the angiogenic pathway as prognostic and predictive factors in breast cancer, and comment on the challenges facing the clinical development and optimum use of these agents.

Surgery is the most frequently used approach in the treatment of nonmelanoma skin cancer, and Mohs micrographic surgery, conventional excision, cryosurgery, or electrodesiccation and curettage are usually performed. Newer noninvasive options include topical chemotherapeutics, biological immune-response modifiers, retinoids, and photodynamic therapy. Neville et al. propose that treatments should be tailored to the tumor type, location, size, and histological pattern, and suggest that, although surgical methods remain the most frequently used, newer noninvasive treatments can be used in select tumors and may reduce morbidity.

There have been considerable advances in our understanding of renal cell carcinoma, which have been translated into the development of several drugs with proven efficacy, with kinase inhibitors demonstrating significant activity. The authors of this review discuss the targeted agents that have proved efficacious in the difficult-to-treat metastatic setting, and highlight the issues of patient selection, scheduling, dose, duration of treatment, potential combinations and toxicity.

Confocal laser endomicroscopy is a new endoscopic tool that allowsin vivo histology at subcellular resolution during ongoing endoscopy, and permits subsurface imaging of normal and neoplastic human mucosa. The authors of this Review highlight why confocal laser endomicroscopy can no longer be regarded as just another endoscopic technique but emerges as a crucial novel imaging technique for in vivodiagnosis of colorectal cancer.

The goal of allogeneic hematopoietic stem-cell transplantation (alloHSCT) in the treatment of hematological malignancies is to harness the graft-versus-leukemia (GVL) effect, while minimizing the risk of graft-versus-host disease (GVHD). AlloHSCT research has focused on the GVL target antigens and effector mechanisms, and on potential approaches to exploit the GVL effect independently of GVHD. In this review, the authors focus on the currently available approaches to exploit these GVL mechanisms and discuss some of the newer approaches that have been explored in clinical practice.

Breast cancer is a heterogeneous group of diseases and hormone receptor status defines important clinical and etiologic differences between breast cancer subtypes. This article reviews the epidemiologic data on differences in risk factor associations by hormone receptor status, and highlights the limitations of commonly used prediction models. The authors describe how receptor status information can be applied to risk analysis for screening and preventive therapies.

Hepatocellular carcinoma (HCC) generally develops as a consequence of underlying liver disease, most commonly viral hepatitis. Currently, surgery remains the treatment of choice for HCC; however, due to underlying liver disease only a minority of those affected are candidates for resection, and access to transplantation is limited by organ availability. The authors of this review discuss when liver resection, nonsurgical HCC treatment and management before liver transplantation should be considered, and the applications of nonsystemic therapies.

Malignant pleural mesothelioma (MPM) is a common primary tumor of the pleura. Current therapeutic regimens that involve surgery, chemotherapy and radiotherapy have offered marginal clinical benefits. Histological subtype, lymph-node involvement, resection margins and invasion beyond the pleura are significant factors that dictate survival. This review discusses the multimodality approach, which is considered the cornerstone of treatment of MPM, although the authors emphasize that the exact combination of treatment options for this disease have yet to be defined.

Brain tumors are currently diagnosed on the basis of their histology, but recent findings indicate that in some cases response to conventional therapy correlates with genetic characteristics rather than histopathology. An understanding of the molecular mechanisms that underlie the malignant phenotype of gliomas also provides the possibility of rational design of molecular targeted therapies, as discussed in this review.