It is recognised that patients treated by orchidectomy and anthracycline-based chemotherapy have an appreciable risk of relapse in the contralateral testis [1, 3, 4, 9, 12, 57, 59, 65, 67, 69, 94, 95]. This presumably reflects poor penetration of commonly used chemotherapy agents into the intact testis. There are no randomised trial data regarding the use of prophylactic testicular irradiation, nor regarding the optimal dose or technique. Available data are derived from retrospective studies and a small number of non-randomised prospective trials. Mazloom et al. reported the MD Anderson Cancer Center experience and found that 3/35 (9 %) patients who did not receive testicular irradiation relapsed in the contralateral testis, compared to 4 % in patients who receive a median testicular radiation dose of 30.6 Gy [11]. Individual series have reported rates of contralateral testicular relapse ranging from 0 to 35 % [96]. In the largest retrospective multicentre series, reported by the IELSG, testicular relapse was a component of 43 of 195 treatment failures, with a 15-year actuarial incidence of contralateral testicular relapse of 42 % in the absence of scrotal irradiation [12]. A number of individual studies have reported a low incidence of testicular relapse following prophylactic scrotal irradiation, typically ranging from 0 to 10 %, though reportedly as high as 20 % in one series, which may reflect uncertainty about the quality of radiotherapy delivery in older series [96, 97]. Prophylactic scrotal radiation in the IELSG retrospective study was associated with a statistically significantly lower incidence of testicular relapse from 42 % to fewer than 10 % (p = 0.011). Importantly, this local control advantage was associated with an improvement in both 5-year PFS (70 % v 36 %, p = 0.00001) and OS (66 % v 38 %, p = 0.00001), which remained statistically significant on multivariate analysis [12]. Other studies have also suggested an association between the use of adjuvant RT and improved survival, although it is uncertain to what extent this reflects patient selection for adjuvant irradiation [2, 98].

Prophylactic testicular irradiation was used in three of the four reported prospective studies of PTL. In two phase II studies reported by Aviles et al., all patients received prophylactic testicular irradiation and no testicular relapses were reported [10, 70]. Similarly in the more recently reported IELSG-10 prospective study, adjuvant testicular radiation (median dose 30 Gy, range 24–40 Gy) was used routinely with no testicular relapses observed [59]. Based on the preponderance of data from both retrospective and prospective trials, prophylactic testicular irradiation is considered standard of care for patients with stage I–II PTL.

Adjuvant scrotal radiation may have a greater impact in patients with limited stage disease, as the competing risks of systemic relapse appear to increase with advancing initial stage. In the IELSG retrospective series, contralateral testicular relapse as a component of the first site of failure occurred in 28 %, 14 % and 16 % of patients with stages I, II and III–IV, respectively. Corresponding figures for sole initial site of failure were 10 %, 2 % and 2 %, respectively [12]. Although the absolute benefit from prophylactic testicular irradiation may be smaller for more advanced stage disease, given the relatively low morbidity of this treatment, it is reasonable to consider it for all patients having potentially curative chemotherapy. Despite the demonstrated efficacy of scrotal irradiation, these findings have not yet been fully translated into routine practice, as the SEER data suggest that only 30–40 % of patients appear to receive RT, without an apparent increase in utilisation over time [2].

The entire testis, tunica albuginea, epididymis and spermatic cord are often reported to be involved in pathological studies of PTL and constitute the CTV for testicular irradiation [62, 96]. In rare cases of overt skin involvement, the skin also forms part of the CTV.

Scrotal irradiation doses reported in the literature have ranged from 18 Gy to over 50 Gy, but are most commonly reported in the range of 25–30 Gy [96]. The prospective studies reported by Aviles and the more recent publication of the IELSG prospective intergroup study both used testicular doses in the range of 25–30 with a high degree of efficacy [10, 59, 70]. As there is some evidence from the IELSG retrospective analysis that doses less than 30 Gy were associated with a lower survival rate, 30 Gy may be considered a reasonable standard of care [12]. Radiotherapy should be fully fractionated to minimise acute scrotal skin morbidity.

Several radiotherapy techniques have been described for irradiation of the scrotum, and as with other aspects of radiotherapy for PTL, they have not been compared in prospective clinical trials. In fact, many reported series either do not describe the techniques used or provide inadequate information on techniques used both for testicular and nodal irradiation. Some older series describe techniques that may have provided inadequate or marginal coverage of the testis [96]. A group of Dutch investigators have reported an extensive review of radiotherapy techniques for PTL, including a survey of techniques used in Dutch centres and a phantom study to compare PTV and critical organ dosimetry using various techniques. The three techniques compared were a direct anterior electron beam, a direct anterior photon beam and a wedge pair photon beam [96]. They found that the most commonly used technique in Holland was an anterior electron beam used in 10 of 16 eligible centres surveyed. The most homogeneous dosimetric coverage of the PTV was achieved using either of the photon techniques, but this came at the cost of higher doses to normal tissues such as anus and rectum. Although the doses to normal tissues were within conventional tolerances, it can be argued, particularly in younger patients, that photon techniques are best avoided to minimise exposure of pelvic and perineal structures in order to minimise the risk of second malignancies. A key message is that the method used in any centre needs to be evaluated carefully from a physics and dosimetric perspective to ensure adequate coverage.

The use of bolus over the scrotal surface is not always clearly described in reports of testicular irradiation for PTL. It should certainly be included in rare cases of overt scrotal skin infiltration to avoid underdosing potentially involved skin. It has been reported that invasion of the tunica albuginea is observed in approximately half of cases of PTL at pathological examination [62, 96]. Given that the skin is only a few mm thick, techniques that spare skin may also lead to underdosing of the tunica and potentially increase the risk of in-field failure.

Patient setup will depend on the technique used. Most surveyed Dutch centres used clinical palpation both to define the CTV and for verification during treatment [96]. Given the variation in scrotal anatomy due to fluctuation in temperature or patient anxiety, clinical localisation may in fact be superior to imaging-based localisation, although CT planning and CBCT verification have been used in some centres and potentially offer better documentation of dosimetry and selection of electron energy [96].

For patients with stage I PTL, radiation is generally confined to the scrotum, and there is no clear role for adjuvant irradiation to apparently uninvolved para-aortic-pelvic nodes. In studies in which scrotal RT only was used for stage I disease, the reported incidence of isolated nodal relapse is low [99].

It is not possible to draw firm conclusions regarding the role of RT to involved regional lymph nodes in patients treated with R-CHOP for stage II disease, because of small numbers of patients reported in the literature with stage II disease treated with or without nodal radiation. Even in the IELSG retrospective study with over 300 cases, it was not possible to make meaningful observations on the role of nodal irradiation in stage II disease [12]. In the IELSG-10 study, of 13 stage II patients, nine received nodal RT, and the single relapse occurred in one of these patients, within the radiotherapy field [59]. The four patients not treated with RT were all in remission at the time of reporting.

The broader literature on the role of adjuvant radiotherapy for DLBCL suggests a benefit for patients with localised and/or bulky disease even in the era of R-CHOP [100–103]. It is uncertain whether the principles of consolidative nodal radiotherapy derived from more common presentations of DLBCL can be translated to the setting of testicular lymphoma, as the pattern of recurrence in PTL is unusual and is dominated by widespread extra-nodal relapse. Despite these caveats, for patients with stage II disease who present with involvement of the pelvic and para-aortic lymph nodes, it is common for adjuvant RT to be delivered to initially involved nodes following chemotherapy, and this may be considered a reasonable standard of care [59]. For patients who present with stage III to IV, the benefit of regional nodal irradiation is even less certain, and radiotherapy would not be used routinely. A possible exception would be cases where there is a dominant sight of nodal disease that is bulky (>7 or 10 cm) or responds slowly or incompletely to initial chemotherapy, particularly in the elderly patient who is unsuitable for aggressive salvage therapy.