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Importance of local control in an era of systemic therapy

Nature Clinical Practice Oncology volume 2, pages 60–61 (2005)Cite this article

Abundant laboratory and clinical research suggests that carcinogenesis is a multi-step genetic process resulting from mutations, which produce the malignant phenotype. The capacities for unlimited proliferation either from loss of senescence or apoptotic potential, and increased angiogenesis, invasion, and distant seeding and growth, are components of tumor progression. Clinical data support the concept that many steps characteristic of malignancy occur during the clinically apparent phase of tumor development.1 Examples of such steps include: in situ tumors becoming invasive; the occurrence of micrometastases without angiogenesis; increases in tumor size, recurrence or progression correlated with an increase in histologic grade; increases in tumor size or progression related to increased metastatic likelihood; and mutations in the genes expressing p53,2 E-cadherin,3 nm234 and loss of function of other genes associated with a poor prognosis. Clinically apparent cancer is best described as a spectrum or continuum of malignant capacities that result from tumor progression by evolutionary means.5,6

Currently cancer is being diagnosed earlier, when there is relatively less malignant potential. This is exemplified by the increase in the diagnosis of in situ and early-stage cancers as a result of improved screening methods and increased public awareness. The current presentation of breast cancer in the US is unlike that seen by Halsted when he described the centrifugal orderly spread of cancer and the resultant therapeutic strategy of en bloc resection. The series described by Halsted comprised patients with locally advanced primary breast cancers, the majority of whom had clinically involved axillary lymph nodes. In contrast, currently more than half of the breast cancer cases seen in the US are either intraductal or stage I tumors. There is also a revolution in tumor imaging that has resulted in better delineation of the primary lesion and earlier detection of metastases. Improved tumor diagnosis has caused significant stage migration with more homogeneous stages and has identified metastases that were previously undetected or had a questionable diagnosis. This is an evolving process, and with PET scanning and molecular imaging just beginning to be utilized in the clinic, even earlier detection and further stage migration can be expected.

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Authors and Affiliations

  1. A.N. Pritzker Distinguished Service Professor in the Department of Radiation at the University of Chicago, IL, USA

    Samuel Hellman

  2. Daniel K Ludwig Professor and Chairman of Radiation Oncology and Head of Molecular Oncology, University of Chicago, IL, USA

    Ralph R Weichselbaum

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  1. Samuel Hellman
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  2. Ralph R Weichselbaum
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Correspondence to Samuel Hellman.

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Hellman, S., Weichselbaum, R. Importance of local control in an era of systemic therapy. Nat Rev Clin Oncol 2, 60–61 (2005). https://doi.org/10.1038/ncponc0075

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