Table 3.
Select studies evaluating adjuvant EBRT ± chemotherapy to the groin or pelvis.
| Study | Treatment years | Patient, n | LND, n | EBRT, n | Age, median (IQR), year | Median follow-up, month | Chemotherapy, n or % | Adjuvant EBRT target |
|---|---|---|---|---|---|---|---|---|
| Demkow, 1999 [75] | 1989–1994 | 64 | 35 | 12 | 64 (21–86) | 33.0 | NACT: 2; CCRT: 3 |
NR |
| Zouhair et al., 2001 [27] | 1962–1994 | 41 | 5 | 14 | 59 (35–75) | 70.0 | No | ILN |
| Chen et al., 2004 [108] | 1989–2000 | 45 | 19 | 9 | 64 (29–87) | 37.0 | CT: 1 | Primary/bilateral ILN and lower iliac LN |
| Langsenlehner et al., 2008 [52] | 1987–2006 | 24 | 8 | Penis/surgical stump (n=14); ILN (n=8) | 62.7 (35.5–90.4) | 58.4 | No | Penis/stump/ILN & iliac nodes |
| Franks et al., 2011 [77] | 2002–2008 | 23 | 14 | 14 | 58 (40–81) | 27.0 | No | Bilateral ILN and PLN |
| Graafland et al., 2011 [73] | 1988–2007 | 161 | 161 | 67 | 64 (33–91) | 60.0 | NACT: 4 | Ipsilateral ILN ± PLN |
| Tang et al., 2017 [84] | 1980–2013 | 92 | 92 | 40 | 65.3 (53–70) | 9.3 | Perioperative CT: 27 | Bilateral PLN |
| Winters et al., 2018 [68] | 1998–2012 | 589 | 589 | 136 | 61.8 (NR) | NR | Perioperative CT: 169 | ILN + PLN |
| Johnstone et al., 2019 [85] | Multi-institutional (NR) | 93 | 93 | 58 | 65.3 (36–90) | 9.4 | Perioperative CT: 46 | ILN ± PLN (ipsilateral if involved) |
| Ager et al., 2021 [87] | 2002–2017 | 146 | 146 | 121 | 59 (54–70) | 10.6 | CCRT: 41% | Ipsilateral ILN ± pelvic LN |
| Choo et al., 2020 [89] | 1995–2015 | 23 | 23 | 11 | 57 (43–68) | 15.8 | CCRT: 11 | Bilateral ILN & PLN |
| Li et al., 2021 [91] | 2003–2015 | 93 | 93 | 32 | 49 (NR) | 8.8 | CCRT: 34% | NR |
| Jaipuria et al., 2020 [90] | 2011–2017 | 45 | 45 | 31 | 56 (45–67) | 12.5 | CCRT: 6 | Bilateral ILN and PLN + suprapubic region |
| Yuan et al., 2020 [123] | 1999–2016 | 51 | 47 | 19 | 61 (37–91) | 36.6 | CCRT: 17; CT alone: 20 |
PLN (n=15); ILN (n=13) |
| Mittal et al., 2021 [78] | 2014–2017 | 14 | 14 | 14 | NR | 24.0 | CT: 14 | Bilateral ILN ± PLN |
| Khurud et al., 2022 [88] | 2010–2018 | 128 | 128 | 78 | 57 (50–65) | 22.0 | CT alone: 19%; CCRT: 13%; CT into EBRT: 24%; CT into CCRT: 12% |
Variable: involved ILN and PLN (68%); involved & uninvolved ILN + PLN (32%) |
| Study | EBRT indication | EBRT technique | EBRT dose to LN | 5-yr CSS | 5-yr OS | 5-yr LRC | EBRT-related toxicity | Misc data |
|---|---|---|---|---|---|---|---|---|
| Demkow, 1999 [75] | ≥2 ILNs or ENE | NR | NR | NR | NR (3-yr: 76%) | NR | NR | LR: 11% (entire cohort) |
| Zouhair et al. , 2001 [27] | (+) surgical margins or lymph node involvement | Parallel opposed AP/PA fields (18 MV); e-field boost for positive nodes | 36–66 Gy/20–36 fx | NR | 57% | 48% | NR | pN2: 7%; pN3: 1% |
| Chen et al. , 2004 [108] | pN+ | Parallel opposed AP/PA field | 40–70 Gy/20–35 fx | NR | 54.30% | NR (3-yr: 89% [AIRT group]) | Grade 3 lymphedema: 22% (AIRT); radionecrosis of inguinal region: 11% (AIRT group) | pN+ (n=17) |
| Langsenlehner et al., 2008 [52] | (+) surgical margins and pN+ | Parallel opposed AP/PA fields; e-field boost for positive nodes | 45–60 Gy/25–60 fx | 84.30% | 56.60% | 100% with AIRT | 10% with persistent lymphedema | Of 12 patients with cN+, definitive EBRT to ILN resulted in 5-yr regional control of 92% |
| Franks et al., 2011 [77] | pN2/3 or ENE | Parallel opposed AP/PA fields; e-field boost for positive nodes | Phase I: 45 Gy/20 fx;Phase II: 12 Gy/5 fx (boost if needed) | NR | NR (3-yr: 66%) | NR (3-yr: 56%) | Scrotal/penile/lower leg lymphedema: 6 | Locoregional relapse-free survival: 56% |
| Graafland et al., 2011 [73] | ≥2 ILNs or ENE | NR | 50 Gy/25 fx | NR | NR | NR | NR | 5-yr ILN recurrence: 16% |
| Tang et al., 2017 [84] | pN3 | NR | 50 Gy/25 fx (n=27);<40 Gy (n=4);>50 Gy (n=5) | 14.4 months | 12.2 months | Adjuvant EBRT with better median time to recurrence (7.7 vs. 5.3 months) | NR | Median PLN+ (n=2);ENE+ in PLN (n=39) |
| Winters et al., 2018 [68] | NR | NR | 75% received ≥45 Gy | NR | 64% | NR | NR | pN2 (n=433) |
| Johnstone et al., 2019 [85] | ≥2 ILNs or ENE | NR | 50 Gy in 25 fx | NR | Median OS: 10.6 months | NR | NR | Median ILN+ (n=4), 72% ENE; median PLN+ (n=2), 49% ENE; median DSS: 11 months |
| Ager et al., 2021 [87] | pN3 | NR | Variable: 45 Gy/20 fx; 54 Gy/27 fx; 50–54 Gy/25–27 fx |
51% | 44% | 56% | NR | ENE: 99% (ILN: 74%; PLN: 25%); 5-yr RFS: 51%; in-field recurrence: 47% |
| Choo et al., 2020 [89] | Regional LN+ | NR | 45 Gy/25 fx (uninvolved LN); 56 Gy/28 fx (involved LN) |
NR (2-yr: 49.3%) | NR (2-yr: 25%) | NR (2-yr: 27%) | Lymphedema: 46%; necrosis: 9% | pN3: 43% |
| Li et al., 2021 [91] | pN3 | Parallel opposed AP/PA fields (equally weighted) | 30–68 Gy/15–34 fx | NR (3-yr CSS: 28.5% [CCRT] vs. 16.2% [CT]) | NR | NR | NR | 21% CCRT underwent salvage surgery |
| Jaipuria et al., 2020 [90] | ≥2 ILNs ± PLN ± ENE | IMRT/VMAT | 45 Gy/25 fx (pelvis); 54 Gy (ENE+ region); 57–60 Gy (gross residual) |
NR | Mean OS: 3.9 yr (RT); mean OS: 2.8 yr (Chemo); median OS not met in PLN-cohort |
NR | 39% of RT group with persistent lymphedema; no RT-related necrosis | Pelvic LN+ (n=13); ENE: 78% |
| Yuan et al., 2020 [123] | NR | NR | 39.6–54 Gy/22–30 fx (PLN); 42.5–64.8 Gy (ILN) |
NR | NR | 2-yr: 54% | G2 skin: 18% (acute); G2 GI; 12% (acute); G1 lymphedema: 18% (late) |
N2/3 (n=23); ENE+: 12% |
| Mittal et al., 2021 [78] | pN3 | IMRT | 50 Gy/25 fx | NR | NR (2-yr: 79%) | NR (2-yr: 79%) | G2 lymphedema: 29%; G3 lymphedema: 0% |
93% received adjuvant and CCRT |
| Khurud et al., 2022 [88] | pN3 | Conventional (54%); 3DCRT (26%); IMRT (20%); |
45 Gy/25 fx; 50.4 Gy/28 fx; 50 Gy/25 fx |
NR | NR (2-yr: 62%) | NR (2-yr: 83% [multi-modal]) | 45% of AIRT group with lymphedema | 2-yr DFS: 55% |
EBRT, external beam radiotherapy; NR, not reported; IMRT, intensity-modulated radiation therapy; CSS, cancer-specific survival; OS, overall survival; Misc, miscellaneous; ILN, inguinal lymph nodes; ENE, extranodal extension; PLN, pelvic lymph node; NACT, neoadjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; CT, chemotherapy; LND, lymph node dissection; LN, lymph node; LRC, local regional control; AP, anterior posterior; PA, posterior anterior; DSS, disease specific survival; DFS, disease free survival; RFS, relapse free survival; VMAT, volumetric modulated arc therapy; RT, radiotherapy; DCRT, definitive chemoradiotherapy; yr, year; Chemo, chemotherapy; AIRT, adjuvant inguinal lymph node EBRT; IQR, interquartile range; fx, fractions.