1. Goodwin, Peter M.

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TURIN, Italy-All patients with stage IIA testicular seminoma should be treated with radiotherapy rather than multi-agent chemotherapy according to conclusions from a study reported at the 2016 Annual Meeting of the European Society for Radiotherapy and Oncology (ESTRO) (Abstract OC-0539).

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"The bottom line results were that in IIA patients radiotherapy did seem to be a better treatment option as far as overall survival was concerned," said Scott M. Glaser, MD, Radiation Oncology Resident at the University of Pittsburgh Cancer Institute, who reported his group's findings-with a median follow-up of just over 5 years-from the National Cancer Database that includes records of 70 percent of all newly diagnosed cancers in the U.S.


He told Oncology Times that the reason his team wanted to look at patients with stage II seminoma was because of the varying treatment options-and heterogeneous practice pattern-in the U.S. in the absence of randomized trial of chemotherapy versus radiotherapy. This had left clinicians with the choice of whether to go for multi-agent chemotherapy or radiotherapy without much hard evidence to go on. "So we wanted to compare those two approaches in a large data set," he said.


While chemotherapy was guideline-based for patients with stage IIC disease (tumors more than 5 cm), the lack of a clear evidence base had led to practice variations for stage IIB disease and even for stage IIA disease (tumors in the lymph nodes less than 2 cm) where U.S. guidelines recommend radiation, Glaser said.


Radiotherapy vs. Chemotherapy

The new study looked at patients with stage IIA and IIB disease separately. It compared survival outcomes among those treated with radiotherapy with those receiving multi-agent chemotherapy using a multivariable propensity-adjusted model that effectively adjusted for confounding factors-such as patient age, insurance status, and comorbidity.


In patients with stage IIA testicular seminoma, radiation therapy clearly gave a better overall survival at five years than chemotherapy (99% versus 93%).


In stage IIB, however, the overall survival was the same with either multi-agent chemotherapy or radiotherapy. "We hypothesized that's due to the competing risk of distant failure in those patients as the tumors in the lymph nodes become bulkier," Glaser said, adding that patients with IIB disease could be subdivided further-with those having smaller tumors responding better to radiation and those with larger tumors benefiting more from systemic treatment-just as in stage IIC disease.


Because the main concerns about using radiotherapy had been about long-term toxicities including second malignancies-well beyond 5 years-Glaser was asked how his recommendation from the study data stacked up against the potential risks ahead for each patient.


"The fact of the matter is [that] when you look at the long-term effects of multi-agent chemotherapy these patients are at risk of long-term side effects of chemotherapy as well," he said, pointing out that, although in patients with stage I testicular seminoma the recommended single-agent single-dose carboplatin chemotherapy was probably less toxic than radiotherapy; in stage II disease-where chemotherapy needs to be multi-agent-the long-term risk was similar to radiotherapy.


Glaser said there had been declining use of radiotherapy for stage II seminoma overall. "However, it appears that there's a survival advantage associated with receiving radiotherapy in the IIA subset. And he added that because of these new findings patients with IIA disease should be preferentially treated with radiotherapy with individual specific decisions taken for those with IIB disease "based on bulk and extent of disease."


Is One Better Than the Other?

Olav Dahl, MD, PhD, Professor of Oncology at the University of Bergen in Norway, who did not work on the study, told Oncology Times he had some reservations about Glaser's conclusions. While the survival data on patients with stage IIA testicular seminoma treated with radiation were similar to historical Scandinavian data, he was not convinced by the findings on chemotherapy. "Ninety-three percent, I think, is too low," he said.


Dahl believed survival with chemotherapy can-and should-be better. "In the results we have presented from Norway and Sweden, we have 99.6 percent survival for all-every stage included," he said.


He agreed long-term effects of radiotherapy should be considered. "We have looked at our data and seen-especially for seminoma-[that] if you go 25-30 years ahead [patients] will have more secondary cancer and more cardiovascular disease. And that is an argument in favor of chemotherapy," he said. This was because the same long-term trend is not seen with chemotherapy. "So, as long as the results in the primary situation is about the same, I will prefer chemo," he said.


Nevertheless, Dahl thought the new analysis confirmed guideline recommendations for patients with IIA disease. "You must expect almost 100 percent survival because if [patients] get recurrence they are treated by chemotherapy and the data here is given by survival and not by control of disease by radiation alone," he said.


Philip Poortmans, MD, PhD, Professor of Radiation Oncology at Radboud University, Nijmegen in the Netherlands and outgoing President of ESTRO, confirmed the use of radiation therapy. "This study clearly shows that in patients with stage IIA [seminoma] radiation at long follow-up offers much better results compared to chemotherapy," he said.


While he acknowledged the standard recommendation in Europe remained a choice of radiation therapy or chemotherapy, he said the new study provided strong support for preferring radiation therapy above chemotherapy. "Of course, this has to be individually evaluated with the patient depending on comorbidity, for example, depending on age," he said.


Peter M. Goodwin is a contributing writer.