4. Discussion

It has been estimated that 10% of perianal abscesses are associated with sexually transmitted infections, tuberculosis, radiotherapy, Crohn′s disease (CD), inflammation, and other conditions [10]. However, 90% of perianal abscesses are caused by cryptoglandular infections [6, 10]. The most widespread etiology of fistula‐in‐ano is that the perianal infection progresses downward to the wall of the anal canal, penetrating any opening or wound in the anal area [8, 11]. Once the infected tract forms, it is sustained by fecal contamination [8, 11].

4.1. Genetic Considerations

Although genetic predisposition is not directly relevant to this patient′s presentation, we briefly reviewed known genetic associations as some reports suggest overlap between inflammatory pathways involved in fistula formation and pathways implicated in prostate carcinogenesis. We found no other reports in the literature that comment on the management or genetic predisposition of concurrent treatment of perianal fistula and prostate cancer without the presence of inflammatory bowel disease [12–16]. Existing literature describes genetic risk factors for prostate cancer and genetic associations with perianal fistula primarily in the setting of Crohn′s disease. NOD2 variants have been associated with Crohn′s disease and perianal fistulizing disease, whereas BRCA1/2, HOXB13, and other inherited variants have been associated with prostate cancer susceptibility [15–20]. However, these associations appear to represent distinct disease pathways rather than an established biologic link between cryptoglandular perianal fistula and localized prostate cancer.

4.2. Radiation and Perianal Fistula

In patients with perianal fistula, pelvic radiotherapy may raise clinical concern as tissue injury, inflammation, fibrosis, and impaired healing could worsen the fistula‐related morbidity or complicate later surgical repair [21]. These concerns are particularly relevant when the fistula tract lies near the anticipated treatment field. For this reason, careful treatment selection, drainage of active fistula disease, radiotherapy planning, and coordination with colorectal surgery are central to management.

For the patient described in this report, the field of radiation had minimal overlap with the field of the perianal fistula, allowing the perianal area to be designated as an avoidance structure during treatment planning. Dose–volume histogram analysis of the contoured fistula/seton region demonstrated a minimum dose of 244.4 cGy, maximum dose of 2644.3 cGy, and mean dose of 697.9 cGy; therefore, the maximum dose to this region was approximately 26.4 Gy (Figure 2B). IMRT was employed to enhance dose conformality and minimize dose to the fistula while maintaining adequate coverage of the prostate target. IGRT using gold coils fiducials further supported target localization and limited unnecessary expansion of treatment margins.

4.3. RA and Radiation Therapy

This patient′s course was complicated by their pre‐existing RA. RA can complicate the administration of radiation therapy due to several reasons. Studies have shown that lymphocytes from RA patients demonstrate increased radiosensitivity and slower DNA damage repair responses compared to those from healthy individuals [22]. Whereas the vast majority of RA patients do not show increased radiation toxicity, a few cases have been reported where RA patients demonstrated significant radiation‐induced toxicity [23].

Moreover, the autoimmune nature of RA meant that the patient′s immune system was compromised, increasing their risk of infections and delayed healing. The chronic inflammatory nature of RA, coupled with the immune system dysregulation it triggers, also increases the risk of scarring and fibrosis following radiation exposure [21].

The pathophysiology of this process involves persistent activation of inflammatory pathways, which leads to the release of profibrotic cytokines such as transforming growth factor‐beta (TGF‐β) [21]. This cytokine promotes the proliferation and activation of fibroblasts into myofibroblasts, which then secrete excessive extracellular matrix components, leading to fibrosis [21]. Additionally, the chronic inflammation associated with RA leads to the accumulation of immune cells, such as macrophages and T cells, which further contribute to tissue damage and fibrosis [21]. Oxidative stress and cellular senescence induced by ionizing radiation exacerbate these effects, making tissues more prone to scarring and fibrotic changes when exposed to radiation [21].

Given these complexities, special adaptations were necessary to ensure the patient′s safety and efficacy of the treatment. To reduce immunosuppression and enhance the patient′s treatment outcome, one of their immunosuppressive medications (abatacept) was discontinued until after their radiation treatment.

Abatacept is an immunosuppressive medication commonly used to treat autoimmune conditions like RA. As T cells are crucial for the maintenance and onset of RA, abatacept functions by inhibiting T‐cell activation, thus managing RA [24]. Radiation therapy on the other hand is used to target and destroy cancer cells. The immune‐suppressing functionality of abatacept risks interfering with the body′s ability to mount an effective immune response against the cancer cells targeted by radiation. To reduce interference, abatacept was discontinued to enhance the effectiveness of radiation therapy for our patient′s prostate cancer.