Is colorectal resection necessary to improve pain and fertility outcomes in patients with deep endometriosis?

Is colorectal resection necessary to improve pain and fertility outcomes in patients with deep endometriosis? Abstract Bowel endometriosis is often considered an indication for extensive surgical management, including colorectal resection, in women undergoing surgery for concomitant endometriosis at other sites. However, several contemporary studies show little or no correlation between the anatomical extent of bowel endometriosis and symptom severity, and current data do not support a direct relationship between bowel disease extent and fertility impairment. Furthermore, the evidence supporting an additional benefit of colorectal resection with respect to pain relief and fertility outcomes remains limited in patients undergoing surgery for deep endometriosis and/or peritoneal and ovarian endometriosis. Notably, when applying strict methodological criteria, only a single comparative cohort evaluated outcomes in women with colorectal endometriosis undergoing surgery with versus without colorectal resection. This cohort did not demonstrate superior pain or fertility outcomes associated with bowel resection. Considering the well-known potential of severe complications of colorectal surgery, these findings challenge the assumption that anatomical completeness equates to clinical benefit. Given the sparse evidence demonstrating a clear proven clinical benefit of adding bowel surgery to surgical removal of endometriosis at other sites, a critical re-evaluation of surgical proportionality is warranted. Robust comparative studies are urgently needed to justify systematic colorectal resection in bowel endometriosis. Key message Despite widespread use, there is minimal comparative evidence that additional colorectal resection improves pain or fertility outcomes in women undergoing surgery for endometriosis at other sites. More high-quality comparative studies are required to justify such interventions, given the well-documented morbidity associated with colorectal surgery. 1 INTRODUCTION Endometriosis prevalence rates range between 1% and 19% in the premenopausal population depending on the study population investigated1, 2 with lower rates of patients finally undergoing surgery for deep endometriosis. The disease is found in over 40% of patients with chronic pelvic pain (CPP)3 with its deep infiltrating variant being present in up to 17% of patients scheduled for assisted reproductive treatment.4 Within this, colorectal deep endometriosis (DE) is commonly perceived as one of the most severe manifestations of DE and is often equated with a need for colorectal surgery, even in the absence of bowel obstruction or severe gastrointestinal cyclic pain symptoms. This practice rests on two assumptions: first, that surgical removal of bowel endometriosis in addition to resection of endometriosis at other sites will relevantly contribute a postinterventional decrease of pain symptoms and second, that removal of bowel disease may contribute to improving fertility outcomes in these patients. Over the past two decades, surgical strategies have evolved from so-called conservative techniques such as rectal shaving and full-thickness resection toward increasingly radical approaches, including segmental colorectal resection with a large body of evidence supporting a short but also long-term benefit with regard to pain relief5-8 and postsurgical improved fertility outcomes following resection of all visible lesions including colorectal DE in affected patients.9 In line with this evidence, current guidelines involving the issue of surgery for colorectal DE list colorectal surgery as a viable treatment option in symptomatic patients wishing to conceive and state that clinicians can consider surgical removal of colorectal DE to reduce pain symptoms and improve quality of life.10 Although this appears effective, severe complication rates including anastomotic leakage, fistula development, or abscess formation range between 2% and 10%.11 Surgical radicality is based on the premise that residual lesions may compromise symptom relief or fertility outcomes. However, one should bear in mind that colorectal surgery for endometriosis is fundamentally different from oncologic bowel surgery as it does not aim to save life. At present, its justification rests entirely on symptom relief and potential fertility improvement. Furthermore, there is evidence that complete resection may not be necessary to effect relevant pain relief.12 Despite the proven benefits of surgery for extensive endometriosis including DE and its colorectal phenotype, direct evidence comparing colorectal resection to leaving colorectal disease completely in situ while resecting all other lesions is extremely limited. A fundamental question consequently arises: is resection of colorectal endometriosis necessary to significantly improve pain and fertility outcomes compared with leaving colorectal disease untreated while addressing all other extraintestinal sites affected? In this commentary, we critically examine whether the systematic inclusion of colorectal resection in surgery for deep endometriosis is supported by comparative evidence on pain and fertility outcomes. 2 COLORECTAL ENDOMETRIOSIS: ANATOMY DOES NOT EQUAL TO SYMPTOM SEVERITY There is conflicting scientific evidence on the correlation of the overall extent of endometriosis and the severity of pain symptoms. Most correlation studies supporting a possible association between the extent of colorectal endometriotic lesions and the location, type, and severity of pain lack control groups. To equate the extent of disease with clinical relevance is problematic. First, endometriosis is a biologically heterogeneous disease, and symptom expression varies widely among individuals. Montanari et al.13 analyzed 245 patients with surgically proven DE and found that a statistically significant but weak correlation was observed between dyschezia severity and lesion size in #Enzian compartment C (rs = 0.334), indicating limited clinical relevance. Pashkunova et al.14 prospectively assessed #Enzian compartment C (rectal) grade and lesion height in 162 women with symptomatic colorectal deep endometriosis and found no direct correlation with dyschezia severity. Likewise, Reiser et al.15 prospectively analyzed associations between symptoms and localization of endometriosis in 521 women with surgically proven endometriosis. Although dyschezia was associated with any variant of DE, again no clear relationship between #ENZIAN-defined presence or extent of bowel disease and any symptom severity was found. These observations undermine the assumption that complete anatomical clearance of bowel disease within surgery for deep, peritoneal, and/or ovarian or uterine endometriosis may not be necessary to achieve symptom relief and highlight the importance of distinguishing association from causation. 3 BOWEL ENDOMETRIOSIS AND FERTILITY IMPAIRMENT: QUESTIONING THE ANATOMICAL ASSUMPTION The relationship between bowel endometriosis and fertility is even less straightforward. While endometriosis in general is associated with infertility in terms of reduced spontaneous conception rates,16 its association with impaired IVF/ICSI outcomes remains a matter of debate16, 17 and may not significantly affect IVF outcomes in the absence of adenomyosis.18, 19 The specific contribution of bowel lesions regarding a reduction of chances of spontaneous pregnancies or success of medically assisted reproduction (MAR) remains unclear. Importantly, there is no high-quality evidence that the presence and/or extent of bowel endometriosis independently impairs fertility. Fertility impairment is multifactorial, influenced by ovarian reserve, tubal function, adenomyosis, age, and male factors. Bowel involvement, by contrast, has not been shown to exert a direct negative effect on ovulation, fertilization, or implantation.18 Despite the widespread adoption of colorectal resection performed as part of surgical clearance of extensive DE in order to improve cumulative pregnancy rates,20 there is a striking lack of comparative data addressing a more fundamental question: does colorectal endometriosis need to be surgically removed at all to improve fertility outcomes when performing surgery for endometriosis?21 4 SURGICAL MANAGEMENT OF COLORECTAL ENDOMETRIOSIS: TECHNIQUE VERSUS NECESSITY The surgical literature on colorectal endometriosis is extensive but conceptually narrow. Most studies compare how bowel lesions should be removed rather than whether they should be removed at all!Randomized trials and large cohort studies by several authors provide valuable insights into surgical morbidity and functional outcomes20 but do not include a true comparator group in which bowel lesions are left completely untouched while removing all other visible lesions. Therefore, they cannot inform the fundamental question of surgical necessity. When the literature is restricted to research only including patients with confirmed colorectal DE including a comparator group undergoing endometriosis surgery without any colorectal intervention reporting postsurgical pain and fertility outcomes, only 1 nonrandomized prospective single-center cohort study arises: Stepniewska et al.22 aimed to determine the influence of removal of colorectal DE in terms of fertility outcomes. The authors compared 60 women who underwent surgery for endometriosis with colorectal segmental resection against 40 patients with evidence of bowel endometriosis who underwent endometriosis removal leaving colorectal DE in situ. After a follow-up of up to 4 years, the monthly fecundity rates differed significantly between women with colorectal resection (2.3%) versus the in situ group (0.8%). Out of these patients, 5/13 (38%) conceived with IVF in group A and 1/13 (8%) in group B. Spontaneous conceptions occurred post surgically in 12/30 (40%) women in group A vs. 7/23 (30%) in group B. Changes in pain symptoms were not reported by the authors. Several limitations of this work need to be highlighted: first, confounding by indication and selection bias have been introduced since group A had more severe symptoms and more stenosis, whereas group B refused bowel resection and exhibited lower average stenosis rates. Second, many key fertility determinants were not evaluated or not well controlled such as the presence of adenomyosis, ovarian reserve or male factor. On the other hand, it should be acknowledged that demonstrating fertility differences in cohort studies is inherently difficult due to multiple confounding factors, including patient behavior during follow-up and the influence of assisted reproductive techniques. Third, no a priori power analysis was reported, and the study was not designed to detect predefined differences in fertility outcomes, limiting the interpretability of the work. Considering evidence showing weak correlations between disease extent and symptoms, and in fact no good evidence on an association between bowel disease and fertility impairment and the absence of adequate comparative data demonstrating superiority of colorectal resection in terms of better pain and fertility outcomes, systematic bowel surgery in patients with extensive endometriosis also raises important medicolegal and ethical considerations. Although the concept of sparing colorectal disease may be difficult to apply to cases where separation of a posterior nodule invading the torus uterinus, the distal uterosacral ligament, the posterior vaginal fornix and the mid-rectum to leave rectal disease behind could also potentially increase the risk of complication, it may be considered in patients with small, nonstenosing lesions located at the sigmoid or upper rectum, where bowel surgery may not be necessary to achieve adequate treatment of other disease sites. Besides, other nonsurgical treatments for colorectal endometriosis such as high-intensity focused ultrasound (HIFU) have been suggested as emerging treatment alternatives.23 5 SUMMARY The surgical literature on bowel endometriosis is extensive, yet it largely addresses the question of how to remove bowel lesions rather than whether they need to be removed. Comparative studies frequently evaluate segmental resection versus disc excision versus shaving, implicitly assuming that bowel intervention is required. In the only comparative cohort including women with colorectal endometriosis undergoing surgery with versus without bowel resection, allocation was driven by symptom severity and patient consent, limiting causal inference and can only be interpreted as a hypothesis-generating study. Hence, the limited available evidence does not support systematic bowel resection in patients undergoing surgery for extensive endometriosis to improve pain or fertility outcomes. Until such evidence emerges, restraint and humility should guide surgical practice. Colorectal resection should possibly be reserved for clearly defined indications such as bowel obstruction, severe stenosis, or refractory and persistent pain symptoms. AUTHOR CONTRIBUTIONS All authors contributed equally to the conception, design, data collection, analysis, and writing of this manuscript. All authors reviewed and approved the final version of the manuscript. ACKNOWLEDGMENTS Open Access funding provided by Medizinische Universitat Wien/KEMÖ. DATA AVAILABILITY STATEMENT Data sharing not applicable to this article as no datasets were generated or analysed during the current study.