Sex Disparities in Rectal Cancer Surgery: An In-Depth Analysis of Surgical Approaches and Outcomes

Abstract

Anatomical and physiological differences exist between sex, leading to variations in how diseases, such as rectal cancer, are prevalence and treatment outcomes of diseases including rectal cancer. In particular, in the case of rectal cancer, anatomical differences may be associated with surgical challenges, and these factors are believed to be important contributors to potential disparities in postoperative recovery, associated complications, and oncological outcomes between male and female patients. However, there is still ongoing debate regarding this matter. Significantly, the male pelvic anatomy is distinguished by its narrower dimensions, which can present surgical challenges and impede visual access during operative procedures, rendering it more complex than surgical interventions in the female pelvis. As a result, this anatomical difference leads to a greater occurrence of postoperative complications, such as anastomotic leakage. Moreover, the pelvis houses nerves that are vital for urinary and genital functions, underscoring the need to assess the potential risks of sexual and urinary dysfunction in rectal cancer surgery. These postoperative complications can significantly impact the quality of life; therefore, it is imperative to perform surgery with an understanding of the structural differences between sexes. Therefore, to address the limitations imposed by anatomical structures, new approaches such as robotic surgery, trans-anal total mesorectal excision, and intraoperative neuromonitoring are being introduced. Furthermore, it is essential to conduct research into fundamental mechanisms that may give rise to differences in surgical outcomes and oncological results between sexes. By comprehending the disparities between males and females, we can advance toward personalized treatments. Consequently, this review outlines variations in surgical approaches, complications, and treatments for rectal cancer in male and female patients.

INTRODUCTION

There are anatomical, physiologic, and metabolic differences between sexes, resulting in sex-specific disparities in the development and treatment approaches of cancer [1]. There are also sex-based differences in the incidence and survival rates of colorectal cancer (CRC) [2,3,4,5,6,7].

Sex differences in adherence to CRC screening, difference in sensitivity to fecal occult blood test which is the most commonly used screening test for CRC, tumor sidedness, genetic mutation, sex hormone have been suggested as factors which were associated with epidemiologic and prognostic difference in CRC according to sex [8,9].

Other than pathophysiological factors, treatment related factors were also pivotal factors influencing prognosis of CRC. A multidisciplinary approach is important when treating colon cancer. The prognosis of CRC is getting better with the advancement of surgical treatment as well as adjuvant treatment [10,11,12]. Therefore, responses to such treatments and adherence to them can influence the prognosis of CRC. Female patients were reported to have shorter duration of 5-fluorouracil chemotherapy [13], more severe toxicity to 5-fluorouracil-based treatment [14]. In many reports, less female CRC patients received adjuvant chemotherapy than male patients [3,13,15] although severe toxicity would related with less receipt of adjuvant chemotherapy of female patients.

Surgery remains a critical component in treating CRC, with its effectiveness influencing prognosis, complications, and functional outcomes. Rectal cancer surgeries in the narrow pelvic cavity have a steep learning curve and are challenged by pelvic complexity [16,17,18]. Sex-based differences impact surgical outcomes, with males at higher risk for postoperative complications, potentially affecting oncological results [19,20,21,22,23]. Genitourinary function differences are under debate. Surgical advances are addressing anatomical challenges, emphasizing the need for patient-tailored treatment alongside disease-focused care.

Therefore, in order to advance to patient-tailored treatment, we must first understand the differences between males and females. In this review, we aim to examine sex differences in surgical treatment outcomes and prognosis.

SEX DISPARITIES IN SURGICAL DIFFICULTY & TYPE OF SURGERIES OF RECTAL CANCER SURGERY

1. Sex-specific anatomical variations and surgical difficulty

The principle concept of rectal cancer surgery is the complete removal of the mesorectal envelope, which is at risk for mesorectal metastases. Precise dissection along these planes and the thorough excision of the mesorectum and its contents are pivotal in minimizing the potential for local recurrence. In rectal cancer surgery, numerous nerve sites are vulnerable to damage, and total mesorectal excision (TME) is designed to excise the tumor-affected area while preserving nerve integrity (Fig. 1) [11,12,24,25].

Fig. 1. Fascial structure around rectum. Total mesorectal excision plane is an avascular area bordered by the mesorectal fascia and the parietal fasica. Adapted from Lee and Kim [25], according to the Creative Commons License.

Sympathetic innervation comes from the superior hypogastric plexus, while parasympathetic innervation comes from the pelvic splanchnic nerves. These nerves join together to create the inferior hypogastric plexus, located along the pelvic side wall (Fig. 2) [25]. The inferior hypogastric plexus, near the mesorectum, must be dissected cautiously. Nerve injuries can lead to urogenital issues like urinary retention, retrograde ejaculation (sympathetic), and impotence (parasympathetic) [24,25,26]. Anatomical challenges during TME can risk nerve injury. Denonvilliers’ fascia, in the anterior region, separates the rectum from adjacent structures and nerves. Staying posterior to it during dissection reduces nerve damage risk (Fig. 3) [27].

Fig. 2. Anatomy of the pelvic autonomic nerves. (A) The inferior hypogastric nerves, found on both sides of the pelvic wall, go down into the deep pelvis and join with sacral parasympathetic nerves from S2–4, creating a mesh-like structure called the pelvic plexus. (B) Pelvic autonomic nerve structures in a cross-section of cadaveric hemipelvis. The inferior hypogastric nerve runs alongside each pelvic wall and combines with sacral parasympathetic nerves, forming the pelvic plexus with nerve bundles extending towards the genital area. (C) The pelvic plexus and neurovascular bundles (NVBs) in laparoscopic view. (D) Robotic view of pelvic cavity. The middle rectal artery originates in close proximity to the pelvic plexus and penetrates through it. Denonvilliers’ fascia seamlessly connects with the right side of the NVBs, which originate from the pelvic plexus. Adapted from Lee and Kim [25], according to the Creative Commons License.

Fig. 3. Dissection plane (blue line) in pelvic cavity of total meorectal resection in rectal cancer. Adapted from Rodríguez-Luna et al [27], according to the Creative Commons License.

The rectal anatomical position in the bony pelvis greatly affects surgical access and mesorectal dissection precision. Patient-specific factors, such as pelvic shape, can complicate rectal cancer surgery. Female pelvises are wider and shorter than male pelvises, providing more space and a broader surgical field for better visibility during surgery (Fig. 4). Pelvimetry, which involves measuring the dimensions of the pelvis through radiology, was initially employed to evaluate the likelihood of a successful vaginal birth [28,29]. More recently, it has been utilized to anticipate the challenges in rectal resection surgery. The differences in pelvicmetric measurements between male and female patients were well recognized, with a significant difference reported in the interspinous and intertuberous transverse diameter of the pelvis [30].

Fig. 4. Bony and soft tissue measurement of pelvimetry with magnetic resonance image of the pelvis (T2-weighted image): (A) interspinous distance, (B) intertubercle distance, (C) mesorectal fat area.

Research has shown a relation between bony or soft tissue pelvic measurements and surgical difficulty including both open and minimally invasive approach (MIS) [28,29,31,32,33,34]. Several factors are used to assess surgical complexity, including circumferential resection margins (CRMs), TME specimen quality, the need for laparoscopic-to-open conversion, the use of transanal dissection to prevent conversion, surgery duration, complications, and intraoperative blood loss.

Zur Hausen et al [35], using CT (computed tomography) scan pelvimetry, found that a smaller obstetric conjugate and a larger sagittal mid-pelvic diameter were linked to a greater risk of incomplete TME, which could affect oncological outcomes. Furthermore, Baik et al [36] conducted an MRI (magnetic resonance image)-based pelvimetric analysis and found that obstetric conjugate and interspinous distance in MRI-based pelvimetry served as predictive factors for the quality of TME. They also identified a short interspinous distance as a predictive factor for a positive CRM.

In addition to the spatial characteristics of the pelvis, there are studies suggesting that muscularity is also related to surgical outcomes [33,34]. Large psoas muscle was known as a good indicator of postoperative outcome in male patients with rectal cancer. An enlarged psoas muscle mass can significantly constrict the pelvic cavity, compounding the challenge in cases where the anatomical space is inherently limited, particularly in males. Surgical procedures within the pelvis, especially TME, become exceedingly complex under such circumstances [35,37]. Some studies have demonstrated an association between whole skeletal muscle mass, an indicator of sarcopenia, and the psoas muscle index (PMI), which is adjusted for height [33,34,38,39]. Mizuuchi et al [33] reported that PMI did not emerge as a risk factor for anastomotic leakage in female patients. A large psoas muscle has a greater impact on men due to their narrow pelvis and larger muscle mass, potentially leading to anastomotic leakage. These sex-based anatomical differences should be considered when planning rectal cancer treatment.

2. Surgical approach and sphincter preservation

MIS has seen significant advancements, particularly over the past three decades in colorectal surgery. MIS has benefits for patients' postoperative recovery and wound management [11,12,24,40,41,42,43]. In addition, laparoscopic approaches allow a magnified view of the pelvis, allowing for more careful dissection of blood vessels and nerves. However, laparoscopic approaches have limitations such as less flexible instruments and two-dimensional screens. Unlike colon cancer surgery, therefore, where the safety and efficacy of laparoscopic surgery were relatively quickly recognized as equivalent, the application of laparoscopic surgery in rectal cancer surgery has shown conflicting results, even in randomized controlled trials (RCTs). In CLASSIC (Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer) trial, laparoscopic approaches were higher involved CRM compared to open surgery. (12% vs. 6%) However, there was no difference between open and laparoscopic approaches in the 5-year overall survival and disease free survival [40]. The COREAN (Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy) trial showed a benefit in less blood loss, postoperative pain, and hospital stay in laparoscopic approaches [41]. On the other hand, there are studies that have not shown that laparoscopic approaches are non-inferior to open surgery. The 2 year disease free survival for laparoscopic surgery patients was 79.5% and for open surgery was 83.2% (95% confidence interval [CI], 78.3–88.3), with no statistical difference found between laparoscopic and open surgery groups [44]. The debate over the superiority of laparoscopic surgery persists, primarily due to the challenges it presents when operating in a confined pelvic space with the presence of the uterus, appendages, redundant peritoneum, and mass [45]. Male had a narrower pelvis and were at risk of postoperative complications compared to female, but there was no difference depending on the surgical method [24]. But, Nasir et al [12] reported that there is a tendency to re-admission in males who underwent laparoscopic surgical resection of locally advanced rectal cancer (odds ratio [OR], 2.23; 95% CI: 1.25–3.99; p=0.613).

Due to these limitations of the laparoscopic approach in rectal cancer surgery, there has been an expectation that the robotic approach would be significantly more advantageous [24,42,46]. Particularly, many surgeons have anticipated that the benefits of robotic surgery would be much greater in cases where difficult surgery is expected. ROLARR (Robotic versus Laparoscopic Resection for Rectal Cancer) trial which is multinational multicenter RCTs comparing the effectiveness and safety of robotic-assisted surgery with conventional laparoscopic surgery in the treatment of rectal cancer, however, failed to demonstrate that the robotic approach was associated with a lower conversion rate than laparoscopic approach [46]. Additionally, the ROLARR RCT did not find any difference in short- and long-term outcomes between the robotic and the laparoscopic approaches [37]. However, conversion to open surgery was significantly higher in male patients (12.3%) than female (5.4%) (p=0.04) in ROLARR trial. It indicates that MIS is difficult to perform in male patients regardless of type of MIS. Another study showed similar postoperative outcomes between the laparoscopic and robotic approaches [39,47]. It cannot be definitively stated that there are differences in postoperative complications and survival rates in rectal cancer surgery depending on the surgical approach. However, REAL (robotic versus laparoscopic surgery for middle and low rectal cancer) trial which was reported from China in 2023, reported that robotic surgery had better recovery and short-term oncologic outcomes than laparoscopic surgery for mid and low rectal cancer. In addition, REAL trial showed advantage of robotic surgery is profound in male patients than female patients. Subgroup analyses showed that CRM positivity was significantly lower with robotic surgery than with laparoscopic surgery for male patients [48].

Sphincter preservation was one of the main interests of patients with rectal cancer. While it might be hypothesized that sphincter preservation could be more challenging in male patients with difficult surgeries, according to existing research, there appears to be no significant difference in sphincter preservation based on sex [32,33,47,49]. Multicenter data including 10 hospitals in the Michigan Surgical Quality Collaborative collected rectal cancer-specific data of patients who underwent rectal cancer surgery from 2007 to 2012 reported that sex was not associated with sphincter preservation. According to this study, hospitals, younger age, and tumor location were associated with sphincter preservation [49].

There have been studies regarding risk factors associated with non-reversal of temporary stomy or permanent stoma among patients who received sphincter preserving surgery [50,51,52]. Barenboim et al [50] showed that only aggressive disease and severe complications of surgery were the major risk factor associated with non-reversal of temporary stomy. Korean single center study also reported that sex was not a determining factor of permanent stoma in rectal cancer patients who received sphincter preserving surgery with defunctioning stoma [51]. Anastomotic leakage (OR, 50.3; 95% CI, 10.1–250.1; p<0.0001) and local recurrence (OR, 11.3; 95% CI, 1.61–78.5; p=0.015) were the independent risk factors.

Recent single center study reported similar outcomes [52]. History of chronic obstructive pulmonary disease, severe postoperative complications according to the Clavien-Dindo ≥3, anastomotic leakage, overall recurrence, and local recurrence were risk factors for permanent stoma in patients undergoing sphincter preserving surgery. Interestingly, they reported that the female sex (p=0.03) was an independent risk factor for the permanent stoma although the mechanism for less sphincter preservation of female patients [52].

Taking these results into account, it becomes evident that factors like the aggressiveness of the tumor, postoperative complications, and recurrence have a more critical impact on sphincter preservation than anatomical considerations.

SEX DIFFERENCES IN SURGICAL OUTCOMES AMONG RECTAL CANCER PATIENTS

1. Surgical complications

Despite significant advancements in surgical techniques, postoperative morbidity following CRC resection continues to pose a substantial challenge [53,54]. Some of surgical complications have been reported to develop with sex difference.

Preoperative obesity in individuals undergoing surgery for CRC was reported to increase the susceptibility to infectious complications in both males and females [19]. Among male patients, a higher body mass index is linked to a greater likelihood of developing surgical site infections and wound infections when compared to female patients with CRC. Therefore, male obese patients should be identified as high-risk candidates for postoperative infectious complications [24].

Postoperative ileus refers to a transient symptomatic disruption in gastrointestinal motility that commonly occurs following abdominal surgery. Some studies showed that male was a risk factor for postoperative ileus of rectal cancer patients (Table 1) [20,21,22,55,56,57,58]. Chapuis et al [20] suggested that this result was due to the fact that open surgery was more common in male patients.

Table 1. Multivariate analyses of predictive factors for postoperative morbidity in males with rectal cancer.

Author	Year	Morbidity	Surgery type	Patients (% of male)	Odds ratio (95% confidence interval)	p-value
Hain et al [56]	2018	Postoperative ileus	Laparoscopic sphincter saving surgery	428 (62.0)	2.3 (1.1–4.5)	0.026
Chapuis et al [20]	2013	Postoperative ileus	All colorectal resection	2,393 (58.2)	1.6 (1.3–2.1)	<0.001
Duchalais et al [55]	2018	Postoperative morbidity	Robotic assisted surgery	183 (68.9)	2.23 (1.10–4.76)	0.030
Degiuli et al [22]	2022	Anastomotic leakage	All rectal resection	5,398 (60.5)	1.55 (1.27–1.88)	<0.001
Park et al [57]	2013	Anastomotic leakage	Laparoscopic resection	1,609 (65.4)	1.94 (1.10–3.42)	0.021
Caulfield and Hyman [21]	2013	Anastomotic leakage	Low anterior resection	210 (51.0)	6.0 (1.4–25.5)	0.020
Jannasch et al [58]	2015	Anastomotic leakage	Anterior resection	17,867 (58.6)	1.92 (1.73–2.13)	<0.001

Anastomotic leakage following rectal cancer surgery represents a critical complication. This complication may be associated with mortality, diminished functional outcomes, and an increased risk of local recurrence [21,57,59]. Male have been identified as a significant risk factor for this leakage following rectal cancer surgery in various studies [21,57,58]. The challenge of operating within the more confined male pelvis, applicable to both open and laparoscopic colorectal surgeries, contributes to this increased risk [60]. Numerous research findings indicate a higher occurrence of anastomotic leakage in males, attributed to the pelvic narrowness complicating surgery and a higher prevalence of comorbidities like tobacco and alcohol use in men compared to female [22,58,61]. Additionally, hormonal variances, particularly in androgens affecting intestinal microcirculation, have been linked to this issue [62].

2. Functional outcomes

1) Defecatory function

Proctectomy leads to inescapable alterations in defecatory function [24,42,59,63]. Following rectal resection, a spectrum of symptoms occurs such as fecal incontinence, constipation, tenesmus, urgency, a sensation of incomplete evacuation, and increased frequency of bowel movements, collectively recognized as the low anterior resection syndrome (LARS). Despite advancements in surgical technique, chemotherapy, and radiotherapy that have increased long-term survival, many patients who underwent surgery for rectal cancer continue to experience alterations in their bowel habits. Sex was not discussed as a risk factor of LARS or showed no significant or consistent association between sex and the development of LARS in previous studies [42,59,63].

2) Voiding dysfunction

Nerve damage, often caused by surgery, can also occur from other treatments like pelvic radiotherapy or chemotherapy. This can cause problems like urinary retention or incontinence, and sexual dysfunctions including erectile and ejaculatory dysfunction. Studies estimate that the incidence of male genitourinary dysfunction after rectal surgeries various ranges between 20% and 80% [64,65,66]. Symptoms of urinary dysfunction in both sexes can include stress incontinence, overflow incontinence, urgency, increased frequency, urinary retention, and incomplete bladder emptying.

Several methods are utilized to evaluate urinary function following rectal cancer surgery [66,67,68]. The International Prostatic Symptom Score (IPSS) was used by most of the authors to assess urinary function. The IPSS is a standardized, patient self-reported measure of the subjective problems that the patient experiences with urinating, with scores ranging from 0 to 35 and higher scores indicating more severe symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms, and 20 to 35 indicates severe symptoms [67]. International Consultation on Incontinence Questionnaire for female or male lower urinary tract symptoms (ICIQ-FLUTS, ICIQ-MLUTS) were also used to screen for urological function. These questionnaires provide a complete assessment of urinary symptoms as well as their impact on the quality of life. The King’s health questionnaire has been validated in male and female. It examines ten factors related to urinary symptoms and their impact on quality of life [68]. Also, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal (QLQ-CR29) was available questionnaire completed by both males and females [69].

Many studies report a decrease in urinary function after rectal cancer surgery, yet research or reports distinguishing or classifying this dysfunction by sex are rare [70,71,72,73,74]. The prevalence of urinary dysfunction following rectal cancer surgery in men, however, compared to women is not conclusively established. While some studies suggest that urinary dysfunction can be more common in men due to factors like the anatomical proximity of the male urinary system to the surgical site.

However, one study used urodynamic tests and ultrasound for comparison and found no significant differences in urinary function between men and women. However, it did show a decrease in the volume of urine voided following surgery [73]. But, Urinary function assessed in males or females in most studies showed no statistically significant differences at long-term follow-up (Table 2) [70,73,74].

Table 2. Postoperative voiding dysfunction after rectal cancer surgery.

Author	Year	Patients (male:female)	Questionnaire for urinary function	Surgery	Preoperative score (male /female)	Postoperative score (postoperative months)	p-value
Kim et al [73]	2012	38:31	IPSS	Robot TME	7.95±5.61	8.2±6.3 (6)	0.908
				Laparoscopic TME	6.43±5.27	8.36±5.5 (3)	0.075
Luca et al [74]	2013	38:36	ICIQ-FLUTS	Robot TME	1.3±1.8	2±2.4 (12)	Not significant
			ICIQ-MLUTS		3.6±3.8	3±3.2 (12)	Not significant
Panteleimonitis et al [70]	2017	84:42	IPSS, King’s health questionnaire	Robot	9.77/8.46	7.69/6.23 (6)	0.023/0.065
				Laparoscopy	6.06/5.31	9.24/7.21 (6)	<0.001/<0.001

IPSS: International Prostatic Symptoms Score, TME: total mesorectal excision, ICIQ-FLUTS/MLUTS: International Consultation on Incontinence modular Questionnaire-Female/Male Lower Urinary Tract Symptoms.

Most studies on postoperative urinary dysfunction compare the superiority between robotic surgery and laparoscopic or open surgery. Multiple investigations have indicated a decline in urinary function following right after surgery [48,70,71,72,75]. However, most studies have shown that urinary function gradually recovers over time after surgery.

There are studies showing that recovery from urinary dysfunction is faster with robotic surgery than with laparoscopic surgery. Kim et al [73] reported a significant increase in total IPSS scores immediately after surgery for both laparoscopic TME and robotic TME groups (7.95±5.61 to 12.79±7.2 and 6.43±5.27 to 11.40±6.62, respectively; p<0.001). However, over time, these scores gradually decreased and reached no significant difference compared to preoperative IPSS scores at 6 months (7.95±5.61 vs. 8.2±6.3, p=0.908) for laparoscopic TME and at 3 months (6.43±5.27 vs. 8.36±5.5, p=0.075) for robotic TME. They also used urodynamic study with ultrasound, it showed reduction in voiding volume after the surgical procedure in both surgical types. But, at 3 and 6 months after surgery, the laparoscopic group showed a greater difference in volume reduction than the robotic group [73]. Study of Balslev and Harling [65], which only compared robotic surgery patients, showed that there was no difference in function between both sex before surgery and one year after surgery. Even in males, there was no difference from before surgery immediately after surgery.

Panteleimonitis et al [70] reported the superiority of robotic surgery. The urinary disorder score in males showed a significant difference in both the laparoscopic group (6.06 to 9.24, p<0.001) and the robotic group (9.77 to 7.69, p=0.023) when compared before surgery and 6 months after surgery. The urinary disorder scores in females showed differences between the laparoscopic group (5.31 to 7.21, p<0.001) and the robotic group (8.46 to 6.23, p=0.065) when compared before surgery and 6 months after surgery. Following the surgery, it was showed that there was an improvement in functionality specifically within the robotic surgery [70].

However, ROLARR trial showed that there was no difference in urinary dysfunction between robotic and laparoscopic surgery (OR, 0.743; 95% CI, -0.587–2.072; p=0.270) [46]. Mercieca-Bebber et al [75] compared open surgery with laparoscopic surgery, and showed that there was no difference between the two groups 3 months after surgery, but urinary dysfunction was more common for open surgery 1 year later. In addition, even one year after surgery, function was shown to be worse than before surgery. Kristensen et al [76] conducted a study on males with CRC. It was shown that the probability of urinary disorders in rectal cancer was much higher than in colon cancer. Additionally, it was shown that abdoinoperineal resection is a risk factor for incontinence and voiding disability for rectal cancer surgery.

Persistent urinary dysfunction following pelvic surgery is a rare occurrence, typically presenting as urinary retention, sometimes accompanied by overflow incontinence. In cases where bladder function fails to recover or patients are unable to engage in chronic intermittent catheterization, long-term solutions such as indwelling catheters or suprapubic catheterization may be considered [77].

3) Sexual dysfunction

There have been a many studies documenting sexual dysfunction as a consequence of rectal cancer treatment [27,64,70,71,73,74,78]. The majority of studies on sexual dysfunction following rectal cancer surgery tend to focus more on male rectal cancer patients. One of the major challenges in this area is the lack of a consistent definition of sexual dysfunction, which makes it difficult to compare findings across different studies. Sexual dysfunction is often defined as a set of specific symptoms that can vary by sex. To assess sexual function, two commonly used tools are employed. The first is the 5-item version of the International Index of Erectile Function, which evaluates erectile function in men. It assigns scores from 5 to 75, with lower scores indicating more severe dysfunction. Common symptoms in men include impotence, ejaculatory dysfunction, and orgasmic dysfunction [79]. The second tool is the Female Sexual Functional Index, used to assess sexual function in women. It uses a scale with scores ranging from 2 to 36, where higher scores indicate better sexual function. Symptoms of female sexual disorders include concerns related to sexual desire, orgasmic dysfunction, and sexual pain [80].

Many studies have explored sexual dysfunction in the context of robotic surgery versus laparoscopic surgery. Most of these studies have not demonstrated any significant advantage of robotic surgery over laparoscopy in this regard [46,71,74]. But, some studies have indicated that robotic surgery leads to a quicker recovery from sexual dysfunction [47,70,73]. Additionally, these studies have found no significant difference in sexual dysfunction outcomes between males and females undergoing this type of surgery (Table 3) [46,47,70,73,74,78]. In a study by Luca et al [74], both male and female participants exhibited a gradual improvement in various parameters over time. One year after surgery, the values were found to be comparable to those observed before the surgical procedure. Specifically, in males, there was a change in values for erectile function (19.1±8.7 to 16.1±10.9) and general satisfaction (6.9±2.4 to 5.7±2.8). In females, changes in values were observed for arousal (2.6±3.3 to 2.3±2) and overall satisfaction (2.4±2.5 to 2.5±2.4) [78]. Panteleimonitis et al [70] conducted a study that revealed sexual dysfunction could manifest six months after laparoscopic surgery. Interestingly, when comparing the changes in sexual function scores before and after surgery, males who underwent laparoscopic surgery exhibited a significant difference (2.31 to 8.56, p<0.001), whereas those who had robotic surgery did not show a significant change (3.62 to 2.92, p=0.759). However, in female patients, there was no notable difference in sexual function scores before and after both types of surgeries (laparoscopy: 3.22–5.22, p=0.154; robotic: 5.75–8.75, p=0.181). Interestingly, the recovery of sexual function appeared to be faster in males after robotic surgery [70]. ROLARR trial found no significant difference in sexual dysfunction between robotic and laparoscopic surgery in both sexes (male: OR, 0.802; 95% CI, -4.100–5.704; p=0.75; female: OR, 1.231; 95% CI, -3.541–6.003; p=0.6). These results suggest that the two surgical approaches did not lead to significant variations in sexual dysfunction outcomes in either sex [46].

Table 3. Postoperative sexual dysfunction after rectal cancer surgery.

Author	Year	Surgery	Patients (male:female)	Questionnaire for sexual function	Follow-up months
Kim et al [73]	2012	Robot vs. Laparoscopic TME	38:31	IIEF	1, 3, 6, 12
Luca et al [74]	2013	Robot TME	38:36	IIEF, FSFI	1, 6, 12
Panteleimonitis et al [70]	2017	Robot vs. Laparoscopy	84:42	IIEF, FSFI	6
Jayne et al [46]	2017	Robot vs. Laparoscopy	320:161	IIEF, FSFI	1, 6
Kim et al [47]	2018	Robot vs. Laparoscopy	103:36	IIEF	3, 6, 12
Li et al [78]	2021	Colorectal surgery	150:78	IIEF, FSFI	12

TME: total mesorectal excision, IIEF: International Index of Erectile Function, FSFI: Female Sexual Functional Index.

Rehabilitating sexual dysfunction after colorectal surgery is a complex task requiring a multidisciplinary approach. It's crucial to begin with psychological assessments and support for both patients and their partners to provide insight and appropriate interventions [81,82]. Regarding pharmacological treatments, a randomized trial by Lindsey et al [83] showed that sildenafil was effective. Among 32 post-rectal resection patients, 80% in the treatment group regained sexual function compared to only 17% in the placebo group. Sildenafil notably improved erectile function scores (OR, 13.3; 95% CI, 7.9–18.7; p<0.001) compared to baseline scores before treatment. Deng et al [84] conducted a trial on the combined use of phosphodiesterase type 5 inhibitors and vacuum erection devices for penile rehabilitation after nerve-sparing radical prostatectomy, suggesting benefits in using one or both of these treatments early in the rehabilitation process.

Pharmacological and sexual device interventions can help individuals or couples with reduced sexual desire and improve sexual function [85]. When pharmacological treatments are ineffective, the implantation of a penile prosthesis is often considered the most effective option, as it is associated with high patient satisfaction [86]. Using lubrication can reduce discomfort during sexual activity, and a structured approach involving gradual vaginal dilation and sensate focus can help break the cycle of dyspareunia, emotional distress, and avoidance of sexual activity [87].

SEX DISPARITIES IN SURVIVAL RATES OF COLORECTAL CANCER

Studies concerning the disparities in survival rates between males and females in CRC have reported varying results, influenced by regional variations and the specific characteristics of each study [3,4,5,7,9]. Most studies are not limited to analyzing differences in survival rates solely for CRC but rather encompass survival disparities across the spectrum of CRC.

A study using data from the US SEER program found that the difference in cancer-specific survival rates between men and women with CRC diagnosed between 1999 and 2003 was particularly more favorable in women when considering clinical and treatment variables [3]. Similar with the earlier study, the survival rates of CRC patients diagnosed between 2004 and 2015 similarly indicated that women had markedly higher cancer-specific survival rates in comparison to males [4]. However, when examining the comparison of CRC disease-specific survival between men and women in Finland from 2006 to 2015, no significant differences in survival were observed [5].

A study examining CRC survival rates in Japan from 1985 to 2004 consistently showed higher survival rates in women compared to men over this period (OR, 0.87; 95% CI, 0.85–0.90; p<0.001) [6]. However, in another study conducted in Japan, which analyzed 62,350 CRC patients diagnosed between 2006 and 2008 across 21 population-based cancer registries, the 5-year survival rate was found to be lower in women compared to men (70.1% vs. 73.9%) [9].

According to Statistics Korea's annual survey based on death certificates, the crude mortality rate for CRCs consistently rose in both men and women from 2000 to 2020. Men had higher crude and age-standardized mortality rates than women, particularly for left-sided colon and rectosigmoid colon cancers. For rectosigmoid colon cancers, both sex saw an initial increase in crude mortality over the first decade, with a slight rise for males in the second decade, while remaining relatively stable for females (Fig. 5) [7].

Fig. 5. Age-standardized mortality rates for males and females. (A) Overall colorectal cancer; (B) right sided colon cancer; (C) left sided colon cancer; (D) rectosigmoid colon cancer. Adapted from Kim et al [7], according to the Creative Commons License.

There have been several studies on sex differences in survival rates in postoperative CRC surgery patients [88,89,90,91]. In almost analysis of overall survival showed a better prognosis for females than for males. But, another study didn’t report sex disparities of survival [91]. Cancer-specific survival also showed different results from study to study. So, further research is needed (Table 4). These differences are thought to be due to anatomical, physiological sex differences, and lifestyle habits.

Table 4. Sexual difference in overall survival and cancer specific survival in colorectal cancer.

Author	Year	Disease	Patients (% of male)	Odds ratio (95% CI) female vs. male		p-value
				OS	CSS	OS	CSS
Paulson et al [3]	2009	Rectal cancer	8,350 (52.0)	0.82 (0.76–0.91)	-	<0.001	-
Berger et al [90]	2016	Rectal cancer	105,511 (58.5)	Stage I–III: 0.78 (0.77–0.80)	Stage I–III: 0.87 (0.84–0.89)	<0.001	<0.001
				Stage IV: 0.96 (0.93–0.99)	Stage IV: 0.97 (0.94–1.01)	0.190	0.160
McArdle et al [88]	2003	Colorectal cancer	3,200 (50;.1)	0.76 (0.68–0.85)	0.84 (0.73–0.98)	<0.001	0.008
Wrigley et al [89]	2003	Colorectal cancer	3,228 (52.1)	0.86 (0.79–0.93)	0.92 (0.84–1.01)	<0.001	NS
Lydrup and Höglund [91]	2015	Rectal cancer	2,792 (42.9)	0.91 (0.82–1.02)	-	0.114	-

CI: confidence interval, OS: overall survival, CSS: cancer specific survival, NS: not significant.

HOW TO IMPROVE SURGICAL OUTCOMES

After surgery for rectal cancer, patients' quality of life decreases. Bowel habit is changed by bowel resection, and genitourinary dysfunction occurs when the nerves are damaged during surgery [90,91].

To overcome this, medical science is constantly advancing. One of them is organ preserving treatment. The goal is to preserve the patient's organs so that their function is as similar as before surgery and to ensure oncological stability [92,93]. The utilization of neoadjuvant chemoradiotherapy has been progressively extended in anticipation of enhancing both sphincter preservation and local control among patients with rectal cancer [92,94]. Watch-and-wait (WW) strategy has been used to treat patients with local rectal cancer with neoadjuvant chemoradiotherapy. Systemic reviews about WW also showed that the WW strategy was not inferior to surgical resection [95,96]. However, some investigators argue that there is still insufficient evidence to enforce WW strategy. It also tends to be reluctant to surgeons yet [97].

There are studies on various approaches for organ preserving surgery. Representative surgical method is the trans-anal approach, which is to perform TME by approaching through the anus [92,93,98,99]. There are several studies showing that oncologic safe is obtained, and functional outcome is not inferior to laparoscopy [98,100]. Anastomotic leak has also been shown to be not inferior to laparoscopy [23,100]. Local excision (LE) is a viable option for clinical T1 rectal cancer with favorable characteristics, offering benefits for anorectal function and reduced morbidity and mortality compared to TME [101]. However, patients who undergo LE without additional treatment have a notable risk of local recurrence or systemic metastasis. It's crucial to select the right patients for surgery, as the LE group may experience increased morbidity when radical surgery is needed due to local recurrence [102]. To mitigate postoperative complications, various approaches, such as modifying suturing techniques and using fluorescence-guided methods to assess anastomotic blood flow, are consistently explored in high-risk populations [103,104,105,106,107].

Since genitourinary dysfunction can occur due to nerve damage, there is a way to prevent it by using intraoperative neuromonitoring, which is confirmed during surgery [108]. Intraoperative neurostimulation results showed a higher sensitivity than visual assessment by the surgeon (82% vs. 46%) [109]. Indications and techniques for autonomic nerve preservation are not yet standardized. But, this may be useful in patients with severe adhesion or a history of previous surgery.

Recently, enhanced recovery after surgery (ERAS) program has shown that early rehab and early feeding in postoperative patients are good prognostic factors for patients' recovery [110,111,112,113,114,115]. The ERAS program recommends catheter removal on postoperative day 1, but surgeons should be taken care when removing it due to the risk of nerve damage during rectal cancer surgery. Long-term catheterization of the catheter causes urinary tract infections and limitations in the mobilization of patients [116]. So, in addition to the ERAS program, the appropriate timing of catheterization should also be considered in patients with rectal cancer [116,117,118]. One study showed that the appropriate time for catheter removal was 3 days of postoperative day [111].

CONCLUSIONS

There are disparities between male and female due to anatomical and physiological differences. Rectal cancer prevalence and mortality vary from study to region. Differences between male and female should be taken into account when operating for rectal cancer to achieve optimal postoperative outcome. Postoperative complications are more prevalent in men, and the possibility of developing ileus and anastomotic leakage should be taken into account. It is necessary to understand these differences between sexes to develop personalized treatment in terms of selection of surgical approach, intraoperative nerve detection method, applying postoperative recovery program, and management of surgical complications.