Year : 2021 | Volume
: 37 | Issue : 2 | Page : 197--198
Approach to chemotherapy for high-risk, stage 1, non-seminomatous, germ cell testicular tumors
Department of Urology and Renal Transplant, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Department of Urology and Renal Transplant, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
|How to cite this article:|
Anand M. Approach to chemotherapy for high-risk, stage 1, non-seminomatous, germ cell testicular tumors.Indian J Urol 2021;37:197-198
|How to cite this URL:|
Anand M. Approach to chemotherapy for high-risk, stage 1, non-seminomatous, germ cell testicular tumors. Indian J Urol [serial online] 2021 [cited 2021 May 16 ];37:197-198
Available from: https://www.indianjurol.com/text.asp?2021/37/2/197/312930
The 111 trial published in European Urology this year examines whether single-cycle Bleomycin, etoposide, platinum (BEP) with etoposide 500 mg/m2 is comparable to two cycles of BEP with etoposide 360 mg/m2, with better toxicity profile; and whether it should be preferred over surveillance for T1 high risk testicular nonseminomatous germ cell testiculars (NSGCTs) and Stage IB nonmetastatic tumors to avoid recurrence. It was a single-arm trial using historical data as control. Patients >16 years age and fit for chemotherapy were included in the study. Patients with previous malignancy, previous chemotherapy, serious comorbidity, neuropathy, pulmonary fibrosis, and impaired liver functions were excluded. Single-cycle chemotherapy with neutropenic sepsis prophylaxis (fluoroquinolones + granulocyte colony-stimulating factors[G-CSF] was administered 6-8 weeks after radical inguinal orchiectomy and followed up with clinical examination, tumor markers, imaging, and toxicity assessment for up to 2 years. A total of 246 patients were accrued, and 228 patients completed the follow-up of 2 years. The trial was powered to exclude a 2-year malignant recurrence rate of 5% with 80% power and 5% alpha. At each recurrence, statistical analysis was performed to keep a check on whether this <5% recurrence target will be achieved with respect to historical controls while preserving the final alpha of 5% and power of 80%. An interim analysis was performed at the completion of 2 years follow-up for 157 patients. Any histological, multiple-site or biochemical recurrence of NSGCT was labeled as malignant recurrence. Single-site recurrence, differentiated teratoma, and non-malignant recurrence were labeled as benign recurrence.
There were a total of four malignant (NSGCT) and three benign (Teratoma) recurrences. Whereas three malignant recurrences were successfully treated with retroperitoneal lymph node dissection and chemotherapy, one patient succumbed to fulminant disease, 9 months after accrual. The long-term toxicity of chemotherapy was low making it an acceptable option. No patient needed to discontinue the chemotherapy due to neutropenia or other serious side effects. The total (benign + malignant) recurrences were <5%. It was concluded that single-cycle high-dose etoposide was as good as two-cycles of low-dose etoposide in preventing recurrence after Stage I high-risk NSGCT and associated with acceptable toxicity, thus making it a viable option in the treatment of such patients outside a clinical trial setting.
Standard treatment for Stage I NSGCT post radical inguinal orchiectomy is surveillance with one or two cycles of chemotherapy as a shared decision-making process as per the latest AUA guidelines, whereas EAU 2020 recognizes the potential of single cycle in reducing the duration of treatment while maintaining its efficacy.,
Chemotherapy duration and the number of cycles advocated in the current guidelines seem to be adequate in advanced cancers but for a subset of patients with Stage I high-risk tumors, two cycles of BEP may be “overkill.” Several small-scale studies have tried shortening the duration of chemotherapy to single cycle., Active surveillance maybe “underkill” with a 50% recurrence rate requiring three cycles of chemotherapy with BEP with significant toxicity. Smaller sample sizes and heterogeneous protocols of these studies prevented single cycle chemotherapy from being considered a standard treatment.
This study provided us with evidence that single-cycle chemotherapy in selected patients may be comparable to two-cycle chemotherapy. The study design could have been better had it included a control group of surveillance only and the third arm of standard two-cycle chemotherapy. Furthermore, neutropenic sepsis prophylaxis with G-CSF and antibiotic as a routine appears to be against the rational use of antibiotics and probably will increase the cost of treatment if compared to selective treatment. A 32% rate of neutropenia and 40% rate of leukopenia with 6.8% severe febrile neutropenia in acute settings also raise questions on the efficacy of this prophylaxis. The effects on fertility and long-term follow-up of this study remain to be seen. It is important to know that a noninferiority trial would have required accrual of 1110 patients, which is difficult to achieve for a subset this specific.
Due to poor adherence and follow-up in India, this regimen may be a useful option to ensure compliance and give comparable long-term outcomes with less toxicity. Some of the questions that may intrigue a researcher are, whether the duration of chemotherapy for non-Stage I NSGCT may also be shortened by increasing the dose of a single agent, or whether this regimen will work on extragonadal NSGCTs. In the current scenario of COVID-19, larger studies will be difficult to perform and probably we will have to wait to see newer studies that address these issues.
Financial support and sponsorship: Nil.
Conflicts of interest: There are no conflicts of interest.
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