Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer

Abstract

Background: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue.

Methods: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread.

Results: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease.

Conclusions: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease.

Keywords: Anal carcinoma; Genital sparing; Intensity Modulated Radiotherapy (IMRT); Lymphatic spread; Marginal miss; Perigenital spread; Vulvar relapse.

Fig. 1

Direct genital infiltration and perigenital involvement and/or perivulvar relapse in anal carcinoma: PET/CT images and clinical manifestation. Legend: (I) Direct genital infiltration in N0/N3 anal cancer at time of first diagnosis (case 1) with PET/CT images in transversal and sagittal planes (Ia, b) and clinical photo (Ic); (II) Vulvar/perivulvar relapse 9 months after concurrent IMRT and chemotherapy of an inguinally N+ anal cancer (case 2) with the CT-sequence of the development of the relapse from time of first diagnosis until 9 months after radiochemotherapy (IIa), pretherapeutic PET/CT images in transversal and coronal planes (IIb, c), IMRT plans in transversal and coronal planes with isodose details (IId, e, f), CT image of the relapse in coronal plane and clinical photo at 9 months after therapy (IIg, h); (III) and (IV) Perigenital involvement related to lymphatic spread in inguinally N+ anal cancer at time of first diagnosis (case 3 and case 4) with PET/CT images in transversal and coronal planes (IIIa, b and IVa, b, c) and clinical photo (IIIc and IVd)

Fig. 2

Perigenital involvement in anal carcinoma: MR images Legend: Representative MR images of case 3 (left) and case 4 (right) in transversal and sagittal planes showing perigenital involvement in anal carcinoma in a T1 weighted sequence after administration of contrast agent