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INTRODUCTION

The use of chemotherapy, targeted therapeutics, and more recently immunotherapy (see Chapter 25) in the treatment of malignant tumors of the genitourinary system serves as a paradigm for a multidisciplinary approach to cancer. The careful integration of surgical and systemic treatments has resulted in impressive advances in the management of urologic cancers. By definition, surgical interventions are directed at local management of urologic tumors, whereas chemotherapy and biologic therapy are systemic in nature. Although there is no question that there are times in the natural history of a genitourinary tumor when only one therapeutic method is required, a multidisciplinary approach is usually beneficial. This chapter details the importance of a joint surgical–medical approach to patients with urologic malignancies. A practicing urologist should collaborate closely with a medical oncologist and should feel comfortable speaking with patients about the uses, risks, and benefits of chemotherapy, and other forms of systemic therapy such as tyrosine kinase inhibitors (TKIs) or immunotherapy. The role of immunotherapy in the management of genitourinary tumors is covered in Chapter 25.

PRINCIPLES OF SYSTEMIC THERAPY

Clinical Uses

Systemic therapy is indicated in the treatment of disseminated cancer when either cure or palliation is the goal. In addition, systemic therapy may be used as part of a multimodality treatment plan in order to improve both local and distant control of the tumor. An understanding of the goals and limitations of systemic therapy in each of these settings is important for its effective use.

A. Curative Intent for Metastatic Disease

Regarding the role of potentially curative systemic therapy in patients with metastatic disease, several factors must be considered. The first is the responsiveness of the tumor. Responsiveness is generally defined by the observed partial or complete responses that together constitute the overall objective response rate. The assessment of neoplasms with frequent bony metastases such as prostate cancer, renal cell carcinoma, and transitional cell carcinoma (TCC) is difficult, as a persistently abnormal bone scan does not necessarily imply residual cancer. Patients in whom the only site of disease is bone generally must be considered nonassessable by conventional measures, and if available, intermediate markers of response (eg, prostate-specific antigen [PSA]) are required. The transient worsening appearance of a bone scan with therapy but that represents healing bone is termed “bone scan flare,” and can be indistinguishable from true disease progression. For this reason, assessment of all parameters including symptomatology, PSA in prostate cancer patients, CT, and MRI is essential. For patients with metastatic prostate cancer in whom bone scan flare is suspected or possible, repeating scans several months later is essential. Increasingly, the ability of an agent to delay objective progression, typically measured as progression-free survival (PFS), has been used as an intermediate marker of responsiveness, although there has not always been an association of PFS with overall survival (OS). If cure is the intent ...

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