|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 24, No 35 (December 10), 2006: pp. 5479-5481 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.09.6602
Advances in Urologic Oncology: Results Progress From Successful Interdisciplinary ResearchDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY INTRODUCTION This is an excellent time to dedicate a Special Series issue of the Journal of Clinical Oncology to the review of germ cell tumors (GCTs), renal cell carcinoma (RCC), and urothelial cancers, and provide the Journal readership with a thorough review of recent gains in both tumor biology and evidence-based clinical treatment. Advances in the standards of cancer care require interdisciplinary collaboration between research scientists who decipher the biology of cancer and clinical scientists who test hypotheses in well-designed clinical trials. Although "bench to bedside" discovery is most commonly discussed, its reciprocal, "bedside to bench" discovery, is equally important. In the case of GCTs, clinical progress was realized decades ago with the introduction of cisplatin-based chemotherapy,1,2 and only more recently were GCT genetic events, such as i(12p), discovered.3 This discovery has since facilitated the identification of GCT among midline tumors of histogenesis and set the stage for a greater understanding of GCT oncogenesis. Conversely, RCC, which was historically characterized by absolute resistance to chemotherapy, now has treatment options based on an enhanced understanding of the Von Hippel-Lindau tumor suppressor gene product and its downstream signaling. As a result, targeted agents are now the standards of care for patients with metastatic RCC. This special issue of the Journal dedicated to these three malignancies will summarize current management strategies based on the conduct of well-designed clinical trials, outline treatment controversies, and review today's understanding of the relevant tumor biology. GCTS Despite its relative rarity, GCT in the adult male serves as a model of curability. The appropriate use of surgery, radiation, chemotherapy, and multimodality approaches has been studied in randomized trials that have successfully established many treatment paradigms. de Wit and Fizazi4 review the controversies and treatment options in the optimal management of clinical stage I seminoma and nonseminomatous GCTs, and provide a detailed overview of the clinical trial results with a discussion of the risks and benefits of surveillance, surgery, radiation therapy (for seminoma), and adjuvant chemotherapy. In the treatment of metastatic disease, the International Germ Cell Cancer Collaborative Group's risk algorithm established international agreement on the clinical features that constitute good, intermediate, and poor prognosis,5 each of which has established standards of care. Kondagunta and Motzer6 update the standards of care for the treatment of patients with both previously untreated and relapsed disease and address controversies such as the use of bleomycin in good-risk disease, the use of high-dose chemotherapy with stem-cell rescue, and postchemotherapy management of advanced seminoma. Oldenberg et al7 review the risk factors associated with, and the clinical management of, late relapse, defined as disease recurrence 2 or more years after primary therapy. Once thought to be an exceedingly rare event, recent reports suggest that late relapses may be more common. An improved understanding of the genetic molecular events that are observed in GCT has emerged in the last two decades, beginning with the observation that an isochromosome of 12p (i[12p]) was frequently observed in GCT. Houldsworth et al provide an overview of the pathobiology of adult GCT, the role of 12p genes implicated in malignant transformation of germ cells, and insights into chemotherapy sensitivity and resistance.8 UROTHELIAL CANCERS Bladder cancer accounts for over 100,000 deaths worldwide annually. In the United States, the incidence of bladder cancer is approximately 50,000 new cases per year, but, more importantly, more than 600,000 patients are currently receiving active care because the majority of tumors are superficial in nature, recur frequently, and have a long natural history. Superficial tumors may progress to a more invasive stage of disease requiring more aggressive treatment to achieve cure, and active and frequent surveillance is mandatory. There is a compelling need for molecular markers to detect recurrent or progressive disease to reduce both the morbidity to the patients and the associated health costs since the gold-standard of cystoscopy and urinary cytology will miss 10% of tumors even in the best care. Black et al9 review the currently available molecular markers, both those approved by the US Food and Drug Administration, as well as those under evaluation. The transurethral resection of the bladder tumor (TURBT) is the mainstay of diagnosis, staging, and stage-directed treatment, and cystectomy is the standard of care for muscle-invasive disease. Bladder cancer is also noteworthy in that it is one of the few malignancies that can be cured with immunotherapy, and the unequivocal benefit of intravesical immunotherapy was established in a randomized trial more than 30 years ago.10 Parekh et al11 comprehensively review intravesical therapy, the role of lymphadenectomy in addition to cystectomy, urinary diversions in the modern surgical era, and the critical role of perioperative chemotherapy. Mitra et al12 review the distinct molecular pathways through which urothelial cancers progress from low-grade tumors (which frequently recur without invasion) to high-grade tumors associated with progression to a higher stage and/or metastatic disease. Although cell cycle regulatory genes such as TP53 and RB have been implicated most frequently, more recent studies show that other molecular alterations, such as p16, p21, and tumor angiogenesis play important roles. Garcia and Dreicer13 review both the state-of-the-art chemotherapy regimens that have evolved since the original study by Sternberg et al, which demonstrated the curability of metastatic transitional cell carcinoma with the M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen,14 and outline the opportunities for novel interventions based on new tumor biology knowledge. Although the historical standard of care for muscle-invasive bladder cancer has been radical cystectomy, major clinical trials have assessed trimodality therapy for bladder preservation—an approach that began as a niche treatment and evolved to an alternative standard of care. Rodel et al15 review the substantial literature on the bladder preservation strategy, summarizing the local control, survival, and quality of urinary function in the preserved bladder, resulting from patient selection, quality of the TURBT, use of chemotherapy, and optimization of external beam radiation therapy. RCC The mainstay of RCC treatment has been surgical management of the primary tumor and metastatic disease, when possible. Randomized trials have addressed the role of cytoreductive nephrectomy, thus providing a framework for state-of-the-art care. Lam et al review these studies and surgical outcomes and address the limitations of the TNM staging system.16 They provide a comprehensive review of integrated staging systems, recently developed prognostic nomograms and predictive prognostic factors, and the potential impact of molecular markers on current staging systems. Immunotherapy has been the mainstay of treatment for RCC, and interleukin-2 (IL-2) is the only treatment that has consistently demonstrated possibly curative benefit in patients with metastatic disease. Yang and Child17 review IL-2 and other immunotherapy approaches, including vaccines, antibodies, and allotransplantation with the induction of graft-versus-tumor response. Parton et al18 review the activity of cytokines and multicytokine combinations and retrospective studies that identify patient populations that are more likely to benefit from immunotherapy intervention. There is every expectation that the treatment of RCC will progress based on our increased understanding of its molecular biology, which has led to the development and US Food and Drug Administration approval of sorafenib and sunitunib in the last year. A third agent, temsorilimus, is pending review based on a randomized trial demonstrating a survival benefit in patients with poor-prognosis RCC. These gains are not restricted to clear-cell carcinoma. Activating mutations in MET are present in hereditary papillary RCC type I, presenting the opportunity for the development of novel agents targeting this alteration. The critical molecular genetic features of RCC are reviewed by Iliopoulos,19 and current and future targeted agents are outlined by Motzer and Bukowski.20 SUMMARY The last two decades in the treatment of these urologic malignancies has been exciting. However, the next decade is expected to be even more exciting due to increasing understanding of the molecular events underlying these malignancies and the development of novel treatments resulting from this understanding. We believe that the contributions of these internationally recognized authors will provide the Journal's readers with both state-of-the-art treatment recommendations for their patients and an understanding of the tumor biology as the era of targeted therapy continues to evolve. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. Author Contributions
REFERENCES
1. Bosl GJ, Motzer RJ: Testicular germ-cell cancer. N Engl J Med 337:242-253, 1997 2. Williams SD, Birch R, Einhorn LH, et al: Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 316:1435-1440, 1987[Abstract] 3. Atkin NB, Baker MC: i(12p): Specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genet Cytogenet 10:199-204, 1983[CrossRef][Medline] 4. de Wit R, Fizazi K: Controversies in the management of clinical stage I testis cancer. J Clin Oncol 24:1-11, 2006 5. IGCCG: International Germ Cell Concensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers—International Germ Cell Cancer Collaborative Group. J Clin Oncol 15:594-603, 1997 6. Kondagunta GV, Motzer RJ: Chemotherapy for advanced germ cell tumors. J Clin Oncol 24:5493-5502, 2006 7. Oldenburg J, Martin JM, Fossa SD: Late relapses of germ cell malignancies: Incidence, management and prognosis. J Clin Oncol 24:5503-5511, 2006 8. Houldsworth J, Korkola JE, Bosl GJ, et al: Biology and genetics of adult male germ cell tumors. J Clin Oncol 24:5512-5518, 2006 9. Black PC, Brown GA, Dinney CP: Molecular markers of urothelial cancer and their use in the monitoring of superficial urothelial cancer. J Clin Oncol 24:5528-5535, 2006 10. Herr HW, Wartinger DD, Fair WR, et al: Bacillus Calmette-Guerin therapy for superficial bladder cancer: A 10-year followup. J Urol 147:1020-1103, 1992[Medline] 11. Parekh DJ, Bochner BH, Dalbagni G: Superficial and muscle-invasive bladder cancer: Principles of management for outcomes assessments. J Clin Oncol 24:5519-5527, 2006 12. Mitra AP, Ram HD, Cote RJ: Molecular pathways in invasive bladder cancer: New insights into mechanisms, progression, and target identification. J Clin Oncol 24:5552-5564, 2006 13. Garcia JA, Dreicer R: Systemic chemotherapy for advanced bladder cancer: Update and controversies. J Clin Oncol 24:5545-5551, 2006 14. Sternberg CN, Yagoda A, Scher H, et al: Preliminary results of MVAC (Methotrexate, vinblastine, doxorubicin, and cisplatin) for advanced transitional cell carcinoma of the urothelium. J Urol 133:403-407, 1985[Medline] 15. Rodel C, Weiss C, Sauer R: Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 24:5536-5544, 2006 16. Lam JS, Breda A, Belldegrun AS, et al: Evolving principles of surgical management and prognostic factors for outcome in renal cell carcinoma. J Clin Oncol 24:5565-5575, 2006 17. Yang JC, Childs R: Immunotherapy for renal cancer. J Clin Oncol 24:5576-5583, 2006 18. Parton M, Gore M, Eisen T: Review article: The role of cytokine therapy in 2006 and beyond for metastatic renal cell cancer. J Clin Oncol 24:5584-5592, 2006 19. Iliopoulos O: Molecular biology of renal cancer and the identification of therapeutic targets. J Clin Oncol 24:5593-5600, 2006 20. Motzer R, Bukowski R: Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol 24:5601-5608, 2006
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
