Radiotherapy with 16 Gy may fail to eradicate testicular intraepithelial neoplasia: preliminary communication of a dose-reduction trial of the German Testicular Cancer Study Group

Abstract

Low-dose radiotherapy to the testis is effective in eradicating testicular intraepithelial neoplasia (TIN, carcinoma in situ of the testis) at the risk of androgenic deficiency. The present trial was designed to define the lowest dose effective to control TIN assuming a doseresponse relation of radiation-induced endocrinological damage. Patients with TIN in a solitary testicle or with bilateral TIN were treated with 18 Gy (14 patients) and 16 Gy (26 patients) (5 Â 2 Gy per week). Biopsies to ascertain clearance of TIN were performed after 6 and 24 months. The median time of follow-up is 20.5 months. There were three adverse events. In one patient, relapse of TIN along with microinvasive seminoma was observed 2 years after 16 Gy irradiation. In two other patients, persistent spermatogonia were observed with the 16 and 18 Gy regimen after 6 and 24 months, respectively. All other post-treatment biopsies showed the Sertoli cell-only pattern. These results confirm that TIN is a radiosensitive lesion efficiently controlled in most cases with doses below 20 Gy. However, sporadic failures may occur. A dose of 16 Gy is probably unsafe and should no longer be used. Future investigations should not only focus on total dosage of irradiation but also on fractionation schedules.

Management and outcome of bilateral testicular germ cell tumors: Twenty-five year experience in Munich

“…However, infertility is an inevitable consequence of low-dose radiotherapy to the testis with Leydig cell function being affected at doses of 14 Á/20 Gy [15]. Recent data indicate that a dose of 16 Gy is probably insufficient in eradicating all malignant cells [16]. Furthermore, there are reports on the development of TGCT despite previous local radiotherapy to the testis [17,18].…”

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: A survey of the German Testicular Cancer Study Group

“…Two major studies yielded conflicting results [14,31]. Possibly, hyperfragmentation of irradiated dosage may afford both an efficacious and less toxic treatment of TIN [49].…”

“…The rationale of radiotherapy is, first, to eradicate TIN cells and second, to preserve the Leydig cells for hormone production ( Figure 1) as well as to preserve the external shape of the scrotum for the preservation of the masculine body image [13]. Irradiation with [16][17][18][19][20] Gy is effective in almost all of the cases [14]. However, impairment of testosterone production is an untoward effect in approximately one-quarter of these patients [15,16].…”

Is a contralateral testicular biopsy in patients with unilateral germ cell testicular cancer indicated as a routine procedure?

“…In our follow-up publication in 2002, all patients treated at dose levels from 20 Gy to 16 Gy obtained complete remission without signs of recurrence after an observation period of more than 5 years, whereas 1 of 14 patients receiving 14 Gy had a relapse of CIS 20 months after irradiation [5]. Other groups have confirmed the efficacy of low dose localized irradiation to eradicate CIS of the testis [6,7], although relapses have also been observed with the use of 16 Gy dose level [8]. Thus, a safe radiation dose is probably 18 Á/20 Gy in 9Á/10 fractions with 5 fractions per week.…”