Isolated testicular relapse

The results of treatment of isolated testicular relapse depend on the timing of the relapse. The 3-year EFS rate of boys with overt testicular relapse during therapy is approximately 40%; it is approximately 85% for boys with late testicular relapse.[225]

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Standard treatment options in North America for childhood ALL that has recurred in the testes include the following:

Chemotherapy.

Radiation therapy.

Standard approaches for treating isolated testicular relapse in North America include local radiation therapy along with intensive chemotherapy. In some European clinical trial groups, orchiectomy of the involved testicle is performed instead of radiation. Biopsy of the other testicle is performed at the time of relapse to determine if additional local control (surgical removal or radiation) is to be performed. A study that looked at testicular biopsy at the end of frontline therapy failed to demonstrate a survival benefit for patients with early detection of occult disease.[226]

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There are limited clinical data concerning outcome without the use of radiation therapy or orchiectomy. Treatment protocols that have tested this approach have incorporated intensified dosing of chemotherapy agents (e.g., high-dose methotrexate) that may be able to achieve antileukemic levels in the testes.

Evidence (treatment of testicular relapse):

The COG AALL02P2 (NCT00096135) trial tested whether radiation therapy could be eliminated for patients with late isolated testicular relapse (occurring more than 18 months from diagnosis).[227] On this trial, testicular size was reassessed after the initial month of reinduction chemotherapy, which included high-dose methotrexate. If the testicle remained enlarged, biopsy was performed, and if positive, patients were to be treated with local radiation therapy. Those with testes that normalized in size or who had negative biopsies were to be treated without radiation therapy. Postinduction chemotherapy for all patients (whether or not they were irradiated) included multiple courses of high-dose methotrexate.[228]

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The COG AALL02P2 (NCT00096135) trial tested whether radiation therapy could be eliminated for patients with late isolated testicular relapse (occurring more than 18 months from diagnosis).[227] On this trial, testicular size was reassessed after the initial month of reinduction chemotherapy, which included high-dose methotrexate. If the testicle remained enlarged, biopsy was performed, and if positive, patients were to be treated with local radiation therapy. Those with testes that normalized in size or who had negative biopsies were to be treated without radiation therapy. Postinduction chemotherapy for all patients (whether or not they were irradiated) included multiple courses of high-dose methotrexate.[228]

Of 40 patients enrolled, 26 had persistent testicular enlargement after reinduction. Testicular biopsy was positive in 12 of these 26 patients, 11 of whom received testicular radiation therapy; all other patients on the trial were treated without radiation.

The COG AALL02P2 (NCT00096135) trial tested whether radiation therapy could be eliminated for patients with late isolated testicular relapse (occurring more than 18 months from diagnosis).[227] On this trial, testicular size was reassessed after the initial month of reinduction chemotherapy, which included high-dose methotrexate. If the testicle remained enlarged, biopsy was performed, and if positive, patients were to be treated with local radiation therapy. Those with testes that normalized in size or who had negative biopsies were to be treated without radiation therapy. Postinduction chemotherapy for all patients (whether or not they were irradiated) included multiple courses of high-dose methotrexate.[228]

Participants who received testicular radiation therapy achieved a 5-year EFS rate of 73% versus 61% for those who did not receive radiation (P = .6); the 5-year OS rate was 73% for those who received testicular radiation versus 71% (P = .9) for those who did not receive testicular radiation.

The COG AALL02P2 (NCT00096135) trial tested whether radiation therapy could be eliminated for patients with late isolated testicular relapse (occurring more than 18 months from diagnosis).[227] On this trial, testicular size was reassessed after the initial month of reinduction chemotherapy, which included high-dose methotrexate. If the testicle remained enlarged, biopsy was performed, and if positive, patients were to be treated with local radiation therapy. Those with testes that normalized in size or who had negative biopsies were to be treated without radiation therapy. Postinduction chemotherapy for all patients (whether or not they were irradiated) included multiple courses of high-dose methotrexate.[228]

Thus, for patients with isolated testicular relapse achieving a favorable response after initial induction (documented by size reduction and/or biopsy), omission of testicular radiation therapy may be a feasible option.

Dutch investigators treated five boys with a late testicular relapse with high-dose methotrexate during induction (12 g/m2) and at regular intervals during the remainder of therapy (6 g/m2) without testicular radiation.[227]

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Dutch investigators treated five boys with a late testicular relapse with high-dose methotrexate during induction (12 g/m2) and at regular intervals during the remainder of therapy (6 g/m2) without testicular radiation.[227]

All five boys were long-term survivors.

In a small series of boys who had an isolated testicular relapse after an HSCT for a prior systemic relapse of ALL, five of seven boys had extended EFS without a second HSCT.[161][Level of evidence C1]

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Isolated testicular relapse

Studies cited in this source section

Publication references