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Authors Kollmannsberger C, Tandstad T, Bedard PL, Cohn-Cedermark G, Chung PW, et al.
Review Date September 2014
Citation Journal of Clinical Oncology 2014 Aug 18. pii: JCO.2014.56.2116. [Epub ahead of print]
Clinical Stage 1 testicular cancer (TC) is defined as cancer confined to the testicle and without serologic, radiographic or clinical evidence of metastases. It is the most common presentation of testicular cancer and most patients are cured following orchidectomy. In recent years, active surveillance (AS) rather than adjuvant chemotherapy or radiotherapy following orchidectomy has become more popular given the high cure rates whatever the treatment, and the desire to reduce treatment-related morbidity.
To define the characteristics of recurrence in TC clinical stage 1 patients on AS in a geographically broad population and to inform the development of AS schedules with respect to timing and type of relapse.
This was a retrospective study including existing data from institutions in Sweden/Norway, Canada, and the United Kingdom. The study included data for 2,483 clinical stage I (CSI) patients: 1,139 CSI non-seminoma; 1,344 CSI seminoma, managed with active surveillance.
Different AS schedules were used at each institution, including physical examination, assessment of tumour markers and chest X-ray/CT scan. Clinical outcomes including relapse and death, time distribution, extent of relapse and method of relapse detection observed on active surveillance were recorded.
Disease-specific survival was measured from the date of orchidectomy to date of disease or treatment-related death or date of last contact. Survival data were analysed using the Kaplan-Meier method.
The 2,483 patients were treated between 1983 and 2012 with most between 1998 and 2010. Median follow-up was 62 months (range: 1-277 months) for non-seminoma and 52 months (range: 1-322 months) for seminoma.
Relapse occurred in 221 (19%) of the 1,139 non-seminoma and 173 (13%) of the 1,344 seminoma patients with a median time to relapse of 4 months (range: 2-61 months), 8 months (range: 2-77 months) and 14 months (range: 2-84 months) for lymphovascular invasion–positive non-seminoma, lymphovascular invasion–negative non-seminoma and seminoma, respectively. Most relapses were observed within the first 2 to 3 years after orchidectomy. Relapses were detected by computed tomography scan in 87% of seminoma recurrences, in 48% of lymphovascular invasion–negative and 41% of lymphovascular invasion–positive patients, respectively. Tumour markers detected 3% of seminoma recurrences, 38% of lymphovascular invasion–negative and 61% of lymphovascular invasion–positive recurrences, respectively.
International Germ Cell Collaborative Group good-risk features were exhibited by 90% of non-seminoma and 99% of seminoma relapses. Seven patients developed a second relapse, 6 after primary radiation and 1 after initial chemotherapy. Three patients with non-seminoma died of disease (0.3%). One patient with seminoma and two patients with non-seminoma died because of treatment-related events. Overall, advanced disease was seen in both early- and late-relapse patients. All late recurrences were cured with standard therapy.
Five-year disease-specific survival was 99.7% (95% CI: 99.4% to 99.9%).
The study showed that active surveillance for CSI testicular cancer leads to excellent outcomes with even the late, unexpected relapses mostly cured. The vast majority of relapses occur within 2 years of orchidectomy for CSI non-seminoma and within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen (1% beyond 3 years). AS schedules should cover the time of significant risk of relapse and the findings suggest that benefit of extending CT/MRI scanning after 3 years is minimal. The data also suggest chest X-ray only contributes minimally to identifying recurrence.
Overall the data indicate that concerns about AS being associated with later or more advanced relapses with worse outcomes are unwarranted.
These data may inform further refinement of rationally designed surveillance schedules to minimize the burden of surveillance investigations for clinical stage 1 testicular cancer.
Points to Note
- This study was based on a large series of patients with testicular cancer form Europe and the UK and showed a very high 5-years survival rate (99.7%)
- 19% of the non-seminoma and 13% of the seminoma patients had a relapse and most occurred within 2-3 years.
- The timing and frequency of abdominal imaging in AS protocols are varied and these data may contribute to defining both the interval and type of investigations performed for seminoma and non-seminoma testicular cancer.
- It should be noted that the data were combined from several centres, with varying AS schedules, different pathology and imaging review and different levels of expertise available which may have impacted on the generalizability of the results.
- On the positive side, it was a very large study with population-based sampling and long follow-up time such that most if not all relapses were identified.
- Studies such as this can help to refine active surveillance protocols to minimise burden of surveillance strategies whilst at the same time maximising cure rates and survival from clinical stage 1 testicular cancer.