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Comprehensive, up to date review. Posting the abstract and discussion sections.
J Clin Oncol. 2006 Dec 10;24(35):5482-92.
Controversies in the management of clinical stage I testis cancer.de Wit R, Fizazi K. Department of Medical Oncology of the Erasmus University Medical Center Rotterdam, The Netherlands. [email protected]
During the last two decades, definitive primary treatments and surveillance with definitive treatment deferred until relapse have demonstrated 98% to 99% cure rates in patients with stage I testis cancer, and these options have obtained firm positions in standard management. The development of optimal management strategies in various countries were at least partly guided by available surgical expertise in retroperitoneal lymph node dissection in the United States, and easy access to reference hospitals in densely populated countries in Western Europe that facilitated close surveillance programs; hence, treatment preferences differ on the two sides of the Atlantic. The success of both approaches is highly dependent on the skills of the practitioner, particularly of surgery and of scrutinized surveillance. As a result, local expertise and familiarity with a chosen modality has strengthened over the years, and investigators have been reluctant to embark on randomized trials designed to compare one modality with another. Such expertise with one particular technique, with the other approach being less familiar territory, has created controversy, because both physicians and patients seek evidence-based data coming from randomized clinical trials on which to make management decisions. Moreover, the reduced risk of relapse resulting from the use of radiotherapy or carboplatin in stage I seminoma and of cisplatin-based chemotherapy in stage I nonseminoma must be balanced against the potential long-term adverse effects in this population of patients with a normal life expectancy. The purpose of this review is to present the currently available data and discuss the merits and the disadvantages of the various approaches, yielding to the possible conclusion that all options appear to be equal in terms of efficacy, but that modality-associated adverse effects differ.
DISCUSSION AND CONCLUSIONS
It appears that all options, both for nonseminoma and for seminoma, provide similar survival rates of 98% to 99%. However, the adverse-effect profiles are distinctly different for each approach.
In the setting of stage I seminoma, prophylactic radiotherapy has a long-standing history as an effective treatment modality, causing modest acute toxicity. More recently, surveillance studies have shown that the risk of recurrence in clinical stage I seminoma is approximately 15% to 20%. Currently available factors predicting the risk of recurrence have not enabled a clinically meaningful discrimination between risk groups. Because there is still a small risk of distant recurrence requiring long-term follow-up and some evidence of secondary malignancies after radiotherapy, surveillance is an alternative option. The main disadvantage of surveillance in seminoma is that, in contrast with surveillance in nonseminoma, relapses may occur beyond 3 to 4 years, hence requiring long-term clinical and radiologic follow-up. The recent report of a European study of a single cycle of carboplatin versus standard radiation therapy demonstrated equivalent 3-year freedom-from-progression rates. This study has been criticized for reporting data after a median follow-up of only 4 years, whether the sample size allowed to test for noninferiority, and whether carboplatin is a sufficiently effective drug in micrometastatic seminoma.53,54 In Europe, adjuvant carboplatin is considered an alternative treatment option. In North America, adjuvant carboplatin remains investigational. Ideally, the patient should be involved in the decision making. Ongoing studies are aimed at identifying occult stage II disease, including the potential role of the PET-scan in clinical stage I seminoma.
In nonseminoma, both primary RPLND and the use of adjuvant chemotherapy result in overtreatment in at least 50% of the patients with clinical stage IB (T2-4N0M0S0) disease. After adjuvant chemotherapy, the risks of relapse after two cycles of cisplatin-based chemotherapy and the relapse with teratoma must be considered. Follow-up in several of the reported chemotherapy series is limited. Of particular concern is the accumulating evidence of clinically significant cardiovascular disease and excess mortality and secondary tumors in long-term survivors. Therefore, extended follow-up is still required.
Surveillance has the benefit of treating only those patients who actually need such treatment, but demands a compliant patient and an experienced clinician. Early detection of recurrence is mandatory to limit the extent of the required intervention. Today, in the setting of low risk for recurrence (clinical stage IA; T1N0M0S0), most investigators will opt for surveillance if logistical conditions allow.
For patients at high risk of recurrence (clinical stage IB; T2-4N0M0S0), nonseminoma with a 40% to 50% risk of recurrence based primarily on the presence of LVI primary RPLND in the hands of an experienced surgeon remains an excellent treatment option, and surveillance in the hands of experienced clinicians and a compliant patient can be an excellent alternative. Adjuvant chemotherapy using two cycles of BEP in high-risk patients reduces the risk of recurrence to approximately 2%. However, the accumulating evidence of excess cardiovascular toxicity together with limited very long-term follow-up should raise concern against the general adoption of this strategy because such treatment will be administered to patients who need no therapy in approximately 50% of cases.
J Clin Oncol. 2006 Dec 10;24(35):5482-92.
Controversies in the management of clinical stage I testis cancer.de Wit R, Fizazi K. Department of Medical Oncology of the Erasmus University Medical Center Rotterdam, The Netherlands. [email protected]
During the last two decades, definitive primary treatments and surveillance with definitive treatment deferred until relapse have demonstrated 98% to 99% cure rates in patients with stage I testis cancer, and these options have obtained firm positions in standard management. The development of optimal management strategies in various countries were at least partly guided by available surgical expertise in retroperitoneal lymph node dissection in the United States, and easy access to reference hospitals in densely populated countries in Western Europe that facilitated close surveillance programs; hence, treatment preferences differ on the two sides of the Atlantic. The success of both approaches is highly dependent on the skills of the practitioner, particularly of surgery and of scrutinized surveillance. As a result, local expertise and familiarity with a chosen modality has strengthened over the years, and investigators have been reluctant to embark on randomized trials designed to compare one modality with another. Such expertise with one particular technique, with the other approach being less familiar territory, has created controversy, because both physicians and patients seek evidence-based data coming from randomized clinical trials on which to make management decisions. Moreover, the reduced risk of relapse resulting from the use of radiotherapy or carboplatin in stage I seminoma and of cisplatin-based chemotherapy in stage I nonseminoma must be balanced against the potential long-term adverse effects in this population of patients with a normal life expectancy. The purpose of this review is to present the currently available data and discuss the merits and the disadvantages of the various approaches, yielding to the possible conclusion that all options appear to be equal in terms of efficacy, but that modality-associated adverse effects differ.
DISCUSSION AND CONCLUSIONS
It appears that all options, both for nonseminoma and for seminoma, provide similar survival rates of 98% to 99%. However, the adverse-effect profiles are distinctly different for each approach.
In the setting of stage I seminoma, prophylactic radiotherapy has a long-standing history as an effective treatment modality, causing modest acute toxicity. More recently, surveillance studies have shown that the risk of recurrence in clinical stage I seminoma is approximately 15% to 20%. Currently available factors predicting the risk of recurrence have not enabled a clinically meaningful discrimination between risk groups. Because there is still a small risk of distant recurrence requiring long-term follow-up and some evidence of secondary malignancies after radiotherapy, surveillance is an alternative option. The main disadvantage of surveillance in seminoma is that, in contrast with surveillance in nonseminoma, relapses may occur beyond 3 to 4 years, hence requiring long-term clinical and radiologic follow-up. The recent report of a European study of a single cycle of carboplatin versus standard radiation therapy demonstrated equivalent 3-year freedom-from-progression rates. This study has been criticized for reporting data after a median follow-up of only 4 years, whether the sample size allowed to test for noninferiority, and whether carboplatin is a sufficiently effective drug in micrometastatic seminoma.53,54 In Europe, adjuvant carboplatin is considered an alternative treatment option. In North America, adjuvant carboplatin remains investigational. Ideally, the patient should be involved in the decision making. Ongoing studies are aimed at identifying occult stage II disease, including the potential role of the PET-scan in clinical stage I seminoma.
In nonseminoma, both primary RPLND and the use of adjuvant chemotherapy result in overtreatment in at least 50% of the patients with clinical stage IB (T2-4N0M0S0) disease. After adjuvant chemotherapy, the risks of relapse after two cycles of cisplatin-based chemotherapy and the relapse with teratoma must be considered. Follow-up in several of the reported chemotherapy series is limited. Of particular concern is the accumulating evidence of clinically significant cardiovascular disease and excess mortality and secondary tumors in long-term survivors. Therefore, extended follow-up is still required.
Surveillance has the benefit of treating only those patients who actually need such treatment, but demands a compliant patient and an experienced clinician. Early detection of recurrence is mandatory to limit the extent of the required intervention. Today, in the setting of low risk for recurrence (clinical stage IA; T1N0M0S0), most investigators will opt for surveillance if logistical conditions allow.
For patients at high risk of recurrence (clinical stage IB; T2-4N0M0S0), nonseminoma with a 40% to 50% risk of recurrence based primarily on the presence of LVI primary RPLND in the hands of an experienced surgeon remains an excellent treatment option, and surveillance in the hands of experienced clinicians and a compliant patient can be an excellent alternative. Adjuvant chemotherapy using two cycles of BEP in high-risk patients reduces the risk of recurrence to approximately 2%. However, the accumulating evidence of excess cardiovascular toxicity together with limited very long-term follow-up should raise concern against the general adoption of this strategy because such treatment will be administered to patients who need no therapy in approximately 50% of cases.
