Prognostic Factors for Renal Cell Carcinoma: Integrating Laboratory and Molecular Factors

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T he study of renal cell carcinoma (RCC), previously viewed as a dormant field due to a paucity of major advances, is no longer your mentor's renal cell carci- noma. It is now center stage in modern oncology due to major advances in molecular genetics and targeted thera- peutic approaches. It has been a preferred cancer for the introduction of innovative minimally invasive approaches, and for attempts to integrate surgery and systemic thera- pies. And yet it is still the urological cancer with the highest cancer related mortality rates, with 40% of patients eventu- ally dying of disease progression. Who is at the highest risk of recurrence or death from this cancer? Until recently this critical question could only be answered in a simplistic man- ner, based primarily upon tumor stage and obvious consti- tutional symptoms such as weight loss or a major decline in performance status. 1 The last 5 years have witnessed a major advance in our ability to prognosticate for patients with renal cell carci- noma, localized or metastatic. Sophisticated statistical anal- yses of large datasets containing clinical, pathological and, in many cases, laboratory factors have now yielded a variety of algorithms that integrate these factors, thereby substan- tially improving prognostic power. 2-4 For patients with met- astatic RCC, these algorithms allow division into groups with low, intermediate and high rates of progression, allow- ing management to be tailored appropriately. Initial obser- vation, active therapy and palliative approaches may apply to each of these groups, respectively. For patients with lo- calized RCC, the ability to segregate based upon risk of recurrence has proven useful for counseling about adjuvant protocols and intensity of surveillance. Such algorithms are now being incorporated into clinical trial design, and are commonly referenced when interpreting or comparing vari- ous conventional and historical studies. In addition to the usual litany of clinical (ie symptomatic presentation) and pathological (stage, grade, presence of histological necrosis, etc) factors, several laboratory factors have also withstood multivariate analyses to qualify as po- tential independent prognostic factors for renal cell carci- noma. These include increased serum levels of lactate dehydrogenase, anemia, increased sedimentation rates and hypercalcemia. In this issue of The Journal Bensalah et al (page 859) add to a growing literature demonstrating a similar status for thrombocystosis. In this study patients with any platelet count greater than 450,000 were approxi- mately twice as likely to die of renal cell carcinoma. This held true for patients with localized disease as well as those with metastases, and thrombocytosis proved to be indepen- dent of stage, grade and performance status on multivariate analysis. One distinct advantage of such laboratory tests is that they are routinely obtained during the evaluation of virtually all patients with this cancer and, thus, add little if