Version of Record online: 13 APR 2007
Volume 99, Issue 5b, page 1201, May 2007
How to Cite
Sternberg, C. N., Vaughan, E. D. and Fitzpatrick, J. M. (2007), Introduction. BJU International, 99: 1201. doi: 10.1111/j.1464-410X.2007.06830.x
- Issue online: 13 APR 2007
- Version of Record online: 13 APR 2007
The special issue of the BJU International is dedicated to RCC, a field in which there has been incredible recent success in the treatment of advanced disease. In addition to the new targeted therapies, the genetic status of several RCC syndromes, current antibody and vaccine approaches, and managing quality of life issues are reviewed in depth.
Validation of therapeutic targets has facilitated new drug discovery, and molecular profiling has paved the way towards progress in better understanding the prognosis, staging and treatment. There is a strong biological rationale for targeting angiogenesis in patients with clear cell RCC via vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and many other signalling pathways, such as platelet-derived growth factor and mammalian target of rapamycin (mTOR).
Targeted therapies provide hope and have proven to have robust activity in several different settings. The results of well-designed randomized phase III landmark trials have shown increases in progression-free survival in the first- and second-line setting, and improved survival in poor-risk patients. The results of two large phase III trials of monoclonal antibody therapy directed against VEGF, combined with interferon are eagerly awaited.
There are no direct comparisons of these agents and all have emerged as promising and viable options in the management of patients with metastatic RCC. It is unknown whether these agents are cross-resistant and whether combined therapies can improve prognosis. It will be important to evaluate how signal-transduction inhibitors and monoclonal antibodies work, through analysis of patients with both responsive and resistant tumours. Identifying drug targets could be improved if specific mutations were found to correlate with drug resistance.
There are many unanswered questions. What is the effect of the novel targets on the primary tumour? Is nephrectomy required in the metastatic setting? Can angiogenesis inhibitors be discontinued after documentation of progressive disease, or is there a ‘rebound’ phenomenon? What is the role of these agents in the adjuvant setting, and in pathologies other than clear cell RCC? Clinical trials of these agents are ongoing in the adjuvant setting to optimize timing, and in the advanced scenario to evaluate sequencing and combinations of therapies.
Immunotherapy with cytokines has been the backbone of treatment for RCC, and can still lead to excellent responses in selected good-risk patients. The advent of newer targeted agents does not eliminate the potential utility of cytokine therapy in RCC, but the role of immunotherapy must be revisited through further investigation into the proper selection of patients and combined therapy to optimize the benefits of cytokine therapy.
It is clear that further exploration of many biological targets continues to provide new insight. Meanwhile, staging and prognostic models have significantly improved the prognostic accuracy. The future portends better molecular characterization of tumours and new rational treatment strategies based on inhibition of specific biological pathways.
The surgical advances have also been numerous. Radical ablative surgery is still the recognised way of removing large renal cancers, but increasingly the less-invasive and nephron-sparing open procedures are being seen as having a significant role in the management of this disease. Partial nephrectomy for small renal cancers, even in the presence of a normal contralateral kidney, have become the norm, and of course the use of laparoscopic procedures, as a method for both radical and partial nephrectomy, have been acclaimed by many as bringing a significant advantage to patients with this disease. Finally, the less-invasive techniques of radiofrequency ablation and cryotherapy are receiving a considerable amount of attention, and are being subjected to stringent clinical review.
We are delighted to bring you this special issue of the BJU International, with all of the above options being discussed in detail, by many of the world experts in this field.