Although the successful multidisciplinary management of testicular cancer is the solid tumor treatment paradigm, challenging cases require detailed knowledge of the disease and therapy options to achieve a successful outcome. Examples of these challenges include primary cisplatin resistance, late relapse, and the growing teratoma syndrome (GTS). Primary cisplatin-refractory disease calls for new therapeutic alternatives, while GTS, if unappreciated, may easily lead to excessive treatment and delayed use of curative surgery. Given the rarity of these events, establishing a "standard of care" is a challenge. However, the skilled clinician with knowledge of the underlying disease and the pathology will be able to successfully manage such patients.
Moore et al use clinical examples of these "difficult" germ-cell tumors to review the complexities encountered in the management of select germ-cell tumors. They thus make a case for surgery as salvage in cisplatin-refractory disease as well as "salvage" from excessive unnecessary chemotherapy in GTS and cystic mature teratoma with moderate marker expression.
The first case presentation is an example of primary platinum resistance. The extent of the recurring disease is limited, making the patient a well suited candidate for a surgical approach. However, the consensus is that a rising serum human chorionic gonadotropin (HCG) level predicts for recurrence and has been considered a contraindication to surgery in this setting.
Experience in platinum-resistant and refractory disease following salvage surgery is suggestive of benefit in roughly one of three patients. Complete resection is the most favorable predictive factor. Unfortunately most patients with primary platinum-refractory disease also have unresectable cancer due to the extent of spread.
It would be of value to the practicing physician to be informed about the more recently introduced chemotherapeutic combinations with potential to overcome cisplatin resistance. It appears that these combinations may lead to an increase in the frequency of successful salvage surgery as part of an integrated treatment algorithm. Promising combinations, such as paclitaxel/gemcitabine (Gemzar), gemcitabine/oxaliplatin (Eloxatin), or paclitaxel/gemcitabine/cisplatin, achieved response rates exceeding 30% in these patients.
In the Murphy et al report, reviewed by the authors in support of the role of salvage surgery in properly selected patients, the occurrence of late relapse was identified as a favorable presurgical characteristic. This finding is in keeping with the widely held view that the mainstay of late relapse therapy is complete surgical removal.[4,5] Late relapse has a unique biology that accounts for the clinical observation. These tumors are slow-growing with a low potential for metastasis to additional anatomic sites and do not respond to chemotherapy with cytoreduction.
The second and third case presentations are ideal tests for the level of diagnostic awareness required by the practicing physician. The implementation of guidelines in disease management is driven by the need to establish a minimum standard of care, and is not meant to establish a strict medical manual. Admittedly, a growing mass in the case of an underlying malignancy should be first considered cancer until proven otherwise. This increased sensitivity, however, should not come at the cost of specificity, leading to subsequent overtreatment and toxicity.
1. Schmoll HJ, Souchon R, Krege S, et al: European consensus on diagnosis and treatment of germ cell cancer: A report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol 15:1377-1399, 2004.
2. Farmakis D, Pectasides M, Pectasides D: Recent advances in conventional-dose salvage chemotherapy in patients with cisplatin-resistant or refractory testicular germ cell tumors. Eur Urol 48:400-407, 2005.
3. Murphy BR, Breeden ES, Donohue JP, et al: Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol 11:324-329, 1993.
4. Shahidi M, Norman AR, Dearnaley DP, et al: Late recurrence in 1263 men with testicular germ cell tumors. Multivariate analysis of risk factors and implications for management. Cancer 95:520-530, 2002.
5. Oldenburg J, Alfsen GC, Waehre H, et al: Late recurrences of germ cell malignancies: A population-based experience over three decades. Br J Cancer 94:820-827, 2006.
6. Beck SD, Foster RS, Bihrle R, et al: Outcome analysis for patients with elevated serum tumor markers at postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol 23:6149-6156, 2005.
7. Stenman UH, Alfthan H, Hotakainen K: Human chorionic gonadotropin in cancer. Clin Biochem 37:549-561, 2004.