Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma

Abstract

Purpose: Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.

Patients and methods: Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.

Results: Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.

Conclusion: Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).

FIG 1.

Patient flow diagram. (*) One patient of the cohort received chemotherapy with temozolomide and a combination of procarbazine, lomustine, and vincristine (PCV) for progressing oligodendroglioma 5 years and 10 months after his NS relapse; because his first relapse was pure teratoma and was treated with surgery alone, because of the long GCC-free interval until initiation of chemotherapy for his second malignancy, and because none of the other patients with pure teratoma relapses experienced a subsequent relapse, it was decided not to exclude this patient from data analysis. (†) Death from oligodendroglioma. (‡) Patient died of sepsis, bleeding, and respiratory insufficiency during high-dose chemotherapy with carboplatin/etoposide.

FIG 2.

Treatment modalities used for treatment of first relapse. RT, radiotherapy; (*) 67% of these patients had teratoma-only relapses.

FIG 3.

Survival of patients. (A) Progression-free (PFS) and overall survival (OS) for all patients. (B) PFS in relation to number of adjuvant treatment cycles. (C) OS in relation to number of adjuvant treatment cycles.

FIG 4.

Outcome in relation to pattern of relapse. (A) Subsequent relapses and outcomes according to the three groups: teratoma-only relapse, early nonseminoma relapse < 2 years after adjuvant treatment, and late nonseminoma relapse > 2 years after adjuvant treatment; (*) oligodendroglioma; one teratoma relapse also occurred > 2 years after adjuvant treatment. NS, nonseminoma; PD, progressive disease; w/o, without. (B) Progression-free survival (PFS) probability in relation to group; (†) PFS event allocated to death from oligodendroglioma. (C) Overall survival (OS) in relation to group; (‡) death from oligodendroglioma.