Viewpoint in 2005

Development of therapies directed to specific molecular abnormalities within cancer cells, as exemplified by human epidermal growth factor receptor 2 (HER2), can be a very rewarding strategy in cancer treatment. The integration of genomic and proteomic approaches into the search for therapeutic targets will be more fruitful than either approach alone and allow further individualization of breast cancer therapy.

Substantial progress has been made using aromatase inhibitors in early-stage breast cancer. This article highlights results from recent and ongoing trials of aromatase inhibitors as adjuvant therapy and discusses options for integration of these agents with tamoxifen in various subsets of patients and clinical scenarios.

The evidence for prostate cancer screening using prostate-specific antigen with reference to UK criteria is presented. Such screening might result in considerable over-diagnosis and over-treatment of clinically insignificant prostate cancer. Morbidity associated with treatment of suspected prostate cancer is substantial, so the likelihood of harm may outweigh the prospect of benefit.

This Viewpoint assesses whether prostate cancer screening within the US is justifiable outside clinical trials. Prostate-specific antigen (PSA) values may fluctuate for physiologic reasons and the natural history of the disease varies between individuals. PSA testing increasingly identifies too many cases of indolent disease that would never have threatened patients' lives.

Evaluating the prognostic value of a tumor marker is an important component of oncology research and has an important impact on treatment decisions. The authors discuss whether the usual statistical approach used to assess prognostic markers can enhance predictive accuracy, and they describe the merits of a more direct approach.

The best practice for use of oncology guidelines is discussed in this Viewpoint article. Clinical practice guidelines should not be used as cost-savings devices, but as tools for ensuring the best care of each individual patient. Guidelines should be accessible, flexible and allow participation of those intended to use them.

In this provocative Viewpoint the authors challenge the concept that patients in clinical trials have a better survival and quality of life than those managed routinely. For instance, phase III trials of breast cancer that restrict access to post-study salvage chemotherapy have yielded 'superior' survival data for investigational drug combinations compared with single-agent therapy, despite poor survival in all cohorts. Should such studies set new standards of care for our patients?

Differences in cancer survival rates throughout Europe are difficult to interpret, but declines in cancer mortality rates from breast cancer and colorectal cancer occurring in many developed countries reflect the great advances in cancer control that have been made in recent years.

Asia, Africa and Latin America are at particular risk of marketing efforts by tobacco companies, with children being the most vulnerable. The Framework Convention on Tobacco Control has now become legally binding in the countries that have adopted it. John Seffrin discusses the global measures designed to prevent tobacco companies gaining a stronghold in developing countries, and reiterates why the US needs to be at the forefront in implementing these measures.

Ablative therapies such as cryotherapy, Mohs' micrographic surgery and radiation have long been considered the standard of care for actinic keratoses and superficial basal cell carcinomas, but imiquimod is now approved for these indications in the US and Europe. Daniel Sauder discusses the mechanisms of action and clinical potential of this promising agent.

The standard of adjuvant therapy for colorectal cancer is still evolving. This is because different combinations of cytotoxic therapies, including 5-FU, oxaliplatin and irinotecan, and biologic therapies, such as bevacizumab and cetuximab, are currently being evaluated. This Viewpoint focuses on the use of shorter durations of adjuvant treatment in order to limit toxicity.

Recent scientific advances have provided new insights into why leukemia is such a difficult disease to treat and identified molecular processes activated in leukemia stem cells that may facilitate their drug resistance and quiescent cell-cycle status. Monoclonal antibody therapy may be appropriate for malignant cells, and other approaches involve identification and targeting of specific survival pathways for these biologically distinct cells, which are discussed in this Viewpoint article.

International consensus has not yet been reached for the use of preoperative chemotherapy for localized esophageal cancer. Chong and Cunningham give an overview of the latest trials and meta-analyses, discussing possible reasons for discrepant findings, and giving their interpretation of best clinical practice for this disease.

This Viewpoint advocates a radical rehaul of the system for describing breast pathology, to echo the classification systems used in other organs. Molecular alterations detected by comparative genomic hybridization highlight some of the deficiencies of the current system for differentiation of different types of breast tumors.

Diagnostic improvements and earlier detection of tumors have resulted in the emergence of a shift from Halsted paradigm, which has encouraged the use of systemic adjuvant therapy. With these changes in tumor paradigm, the rationale for local treatment as a curative treatment strategy has been challenged. This Viewpoint emphasizes the importance of local control in this scenario.

Hodgkin's lymphoma has become a curable disease successfully treated using dose-escalated BEACOPP chemotherapy regimens pioneered by the German Hodgkin's Lymphoma Study Group. However, the unacceptable side effects of chemotherapy have propagated new therapeutic concepts based on biological characteristics of the disease to be explored. This viewpoint discusses the promises and pitfalls of targeted therapy.

The combination of transurethral resection of the bladder tumor (TURBT), chemotherapy, and radiotherapy in selected patients with bladder cancer may result in survival rates comparable to the best cystectomy series, while preserving bladder function. This Viewpoint article discusses the role radiotherapy plays in this approach.