Age

Although bowel dysfunction is more prevalent in the general elderly population, age does not significantly affect the incidence of post-treatment bowel dysfunction. Some research has found that younger patients report worse function, possibly because it affects their QOL more profoundly. Although elderly patients score slightly worse on functional and role domains of QOL metrics, worsened functional outcomes have not been documented in older patients. Further systematic study is needed.

Gender

Whether there is a gender difference in bowel dysfunction after therapy remains unclear. Data comparing bowel function after rectal cancer therapy by gender are mixed, with some studies reporting greater dysfunction in women, some reporting greater dysfunction in men, and some reporting no difference. It is possible that preexisting subclinical sphincter injuries exist more commonly in women due to childbirth, predisposing women to worse postoperative bowel function. To date, however, there have been mixed data supporting or refuting differences in function based on gender.

Preoperative function

Preoperative bowel function should intuitively play a role in post-treatment bowel function. In assessment for sphincter-preservation, an understanding of each patient’s current function is crucial to making appropriate recommendations. Pretreatment function has not been well measured, however, and further research is necessary to determine the magnitude of this relationship.

Tumor level

The level of tumor and its unique effect on function is under-reported. Using the level of the anastomosis as a surrogate for tumor height, tumor level appears to be one of the most important factors affecting post-treatment bowel function. Lower tumors require more extensive and challenging dissection, which incurs an elevated risk of injury to the autonomic nerves, pelvic floor, and anal sphincter. Many studies have confirmed the relevance of anastomotic height to subsequent function, and some have found the effect so strong as to be the only predictor of dysfunction or the best predictor of postoperative improvement. Frequency, incontinence, emptying problems, and difficulty discriminating stool from gas increase significantly if the anastomosis is located 3 to 7 cm from the anal verge. ISRs required for low tumors may pose a particularly high risk of incontinence, embarrassment, and reliance on medication ; meta-analysis demonstrates significant rates of incontinence (49%), soiling (29%), urgency (18%), and medication reliance (18%) after ISR. Tumor proximity to the anal verge and subsequent anastomotic height are key determinants of postoperative bowel function and must be considered in patient counseling and treatment planning.

Tumor stage

The effect of stage on bowel function is difficult to separate from the effects of stage-specific treatments. As tumors become bulkier (ie, T4 lesions), the need to resect additional anatomic structures may have a further impact on functional outcomes. In patients with stage II or III tumors, however, it is difficult to isolate the impact of stage from other factors, such as radiation, and the unique affect of tumor stage on bowel function remains difficult to describe.

Open versus minimally invasive technique

Whether differences in visualization, tactile sensation, retraction, or maneuverability in open, laparoscopic, or robotic surgical approaches translate to differences in postoperative bowel function remains poorly understood. Several randomized studies have evaluated inpatient milestones, perioperative and longer-term oncologic outcomes associated with open versus laparoscopic rectal surgery, but no study has rigorously evaluated functional outcomes. Early data from the COLOR II trial suggest that no difference has been seen in functional outcomes at 12 months postoperatively, but further research is needed. Data from the multicenter randomized ACOSOG Z6051 trial are awaited and may provide additional insight.

TME and non-TME approaches

TME is considered the gold standard for the surgical treatment of most rectal cancers, and modern functional outcomes are generally reported in patients who have undergone TME. In two instances, functional outcomes have been reported for nontraditional TME surgical procedures for rectal cancer.

Extended lateral pelvic lymph node dissection (ELND) in locally advanced cancer is not practiced routinely in North America but has been used more extensively in Asia. The literature on subsequent bowel function is limited but suggests that physiologic parameters of evacuation are not negatively affected. This work is significantly confounded, however, by increased use of radiation, J pouch, and autonomic nerve dissection in patients requiring lymph node dissection.

Transanal endoscopic microsurgery (TEM) may be a viable excisional approach in select cases of rectal cancer. Although the data on functional outcomes are limited, and no direct comparison with proctectomy exists, TEM seems to produce good functional results, resulting in mild bowel dysfunction that improves after 3 to 12 months and returns to baseline, with maintenance of high QOL. Given its favorable functional profile, transanal excision should be considered an option in oncologically appropriate cases, although further research is necessary.

Reconstructive techniques

Decisions regarding the method of restoring bowel continuity after proctectomy can significantly affect subsequent bowel function. Restorative methods are of particular importance to surgeons because of their discretionary nature and afford an opportunity to positively influence subsequent function. For this reason, many high-quality studies have been performed examining function after specific reconstructive techniques.

Hand-sewn versus stapled anastomosis

Restorative bowel anastomoses were traditionally performed using suture, but the development of complex bowel staplers have made stapled anastomoses increasingly popular, and their adoption has been facilitated by studies reporting similar function between hand-sewn and stapled anastomosis. A recent randomized trial also found no difference in function. In modern series, patients with hand-sewn anastomosis typically have worse function, but this is most likely due to the use of suture as a proxy for a very low anastomosis. Therefore, ease of anastomosis with suture or stapler is likely the best determinant of method.

Restorative pouches

The straight end-to-end anastomosis has been noted to result in significant frequency, urgency, and clustering, likely due to smaller capacity, distensibility, and increased peristaltic motility compared with native rectum. Therefore, neorectal reconstructions, such as the side-to-end anastomosis, J pouch, and coloplasty pouches, have been devised in an attempt to better restore function, and several studies have evaluated their relative merits.

Many trials have found the J pouch functionally superior to the straight anastomosis. J pouch is associated with 50% fewer bowel movements and less nocturnal frequency, urgency, incontinence, clustering, retention, medication reliance, need for dietary restriction, difficulty with discrimination, capacity, and compliance. The superiority of the J pouch may increase with proximity to the anal verge ; thus, patients with anastomoses less than 4 cm from the anus may benefit most. These advantages last at least 18 months after surgery. Data on longer-term outcomes are mixed. Some studies report equalization over time, whereas others report continued superiority at 5 years. The J pouch balances storage and expulsion best when 5 to 6 cm in length, and sigmoid and descending colon J pouches function equally well. There are some reports of increased need for enemas with a pouch, especially pouches longer than 5 cm. Overall, the J pouch seems to provide better function than straight anastomosis; however, construction of a J pouch is not always technically feasible.

Other pouch options exist. The transverse coloplasty pouch has shown functional equivalence to the J pouch in some randomized studies. In a large, well-controlled randomized study, however, Fazio and colleagues found it to have inferior functional results compared with the J pouch. Ho and colleagues reported a high leak rate (16%) occurring at the antimesenteric side of the end-to-end anastomosis. Another option, the side-to-end anastomosis, requires less physical space and is easier to construct than the J pouch, with fewer staple lines. Side-to-end anastomosis has been shown to produce better functional outcomes than the straight end-to-end anastomosis and similar results to the J pouch, although the J pouch demonstrated mildly better recovery of capacity and better evacuation at 6 months. Despite these data, the transverse coloplasty pouch and side-to-end anastomosis have not been as widely adopted as the J pouch.

In summary, all neorectal constructions seem to provide better function than the straight end-to-end anastomosis for at least the first 12 to 24 months postoperatively. The J pouch reconstruction seems associated with slightly better recovery than the side-to-end anastomosis but is more bulky. The J pouch produces fewer leaks, and likely better function, than the coloplasty pouch. Additional long-term outcome data are required in order for us to better understand the durability and function of various pouch reconstructions.

Diverting ileostomy

Although diverting ileostomy has been shown to decrease postoperative ileus, reoperation, anastomotic leak, and pelvic sepsis, diversion has unclear effects on long-term function. Diversion has the potential to cause atrophy, stricture, or disuse colitis, which could affect longer-term postoperative bowel function. Diversion colitis is associated with worse function at 6 months after stoma closure, and meta-analysis has demonstrated increased anastomotic stricture in diverted patients. A large retrospective study demonstrated equivalent functional outcomes, however. More rigorous data on the functional consequences of diversion are needed to elucidate this relationship.

Radiotherapy

Several large, multicenter randomized trials have found that radiotherapy (RT) is a highly significant risk factor for postoperative bowel dysfunction, with more patients suffering from urgency, frequency, and dependence on antidiarrheal medications even 12 to 24 months after treatment. The Dutch TME trial, using patient-reported instruments, demonstrated higher rates of fecal incontinence (62% vs 38%), higher frequency of bowel movements (3.7 vs 3.0 daily), and greater pad dependence even at 5 years postoperatively in patients randomized to preoperative RT. Meta-analysis has shown a risk ratio of 1.67 for incontinence with neoadjuvant RT versus surgery alone as well as worsening of manometric anorectal function measurements.

Timing of RT may also affect function. Results of the German Rectal Cancer Study Group trial indicate decreased gastrointestinal toxicity in preoperative RT compared with postoperative RT, with significantly less acute diarrhea (12% vs 18%) and less long-term gastrointestinal dysfunction (composite of diarrhea and small bowel obstruction; 9% vs 15%) in the preoperative RT group.

RT causes significant bowel dysfunction, and the functional consequences of RT should be considered when planning treatment of rectal cancer. Data on function in patients treated with initial nonoperative management remains to be seen. Studies such as the Alliance PROSPECT trial, which is evaluating the role of selective radiation, may provide important information on decreasing long-term sequelae of treatment while maintaining good oncologic outcomes.

Chemotherapy

There are few studies evaluating the long-term effects of modern neoadjuvant or adjuvant chemotherapy, but investigation of the consequences of combined chemoradiotherapy (CRT) have not shown differences in incontinence or frequency. A randomized trial comparing RT to CRT and evaluating QOL is currently being conducted in Germany. Adjuvant chemotherapy, such as oxaliplatin, although known to have neurotoxicity, has never been studied as an independent factor in bowel dysfunction. Although the current body of literature is limited, the impact of chemotherapy on long-term function is likely overshadowed by the effects of radiation when given in combination.

Age

Age has been shown to affect sexual activity in the general population. Despite a possible increase in sexual activity in the geriatric population with the increasing availability of pharmacologic aids, a reference sample published in 2007 found rates of sexual activity to decrease with age: from 73% to 53% to 26% in populations aged 57 to 64, 65 to 74, and 75 to 85 years, respectively. Findings by Hendren and colleagues support this result, documenting, by linear regression, a year-by-year odds ratio of 0.94 of continuing sexual activity with advancing age. Other studies have concurred, finding an independent association between age and poor sexual function postoperatively. A study using a modified version of the European Organisation for Research and Treatment of Cancer (EORTC) instrument found that younger patients experienced higher levels of “personal strain” due to postoperative sexual dysfunction than older patients. Younger patients are more likely to be sexually active and also more likely to suffer due to postsurgical impairment of their sexual function. These considerations are important when comparing studies of sexual function after cancer treatment and also during patient counseling and treatment planning.

Gender

Assessing the effects of gender on post-treatment dysfunction is particularly challenging. There may be an elevated risk of nerve damage during dissection in the narrow male pelvis, but because of differences in the details and assessment instruments of male and female dysfunction, direct comparison has not been effective. Postoperative dysfunction has been studied more extensively in men, and evidence in women has been particularly poor for several reasons, including issues in measurement (the older EORTC QLQ-CR38 module systematically excludes information from sexually inactive women), lower response rates to surveys of sexual function among women, and the discrete nature of male dysfunction. More study of female sexual dysfunction, as well as an instrument that allows comparison with men, is needed to determine if there is a gender bias in post-treatment dysfunction.

Preoperative function

Preoperative sexual activity and function can be expected to be major determinants of postoperative dysfunction, but few studies have adequately measured preoperative function or assessed the relationship. Patients who are inactive preoperatively rarely become active postoperatively; in a bi-gender sample, Hendren and colleagues found that preoperative activity was the strongest predictor of postoperative activity, with an odds ratio of 37.8, underscoring the importance of its assessment. More recently, others have also found that preoperative dysfunction predicts dysfunction at 3 and 6 months postoperatively. To adequately understand the effects of treatment, the preoperative sexual activity and functionality of patients must be considered.

Tumor level

Tumor height determines depth and difficulty of dissection and, thereby, potentially affects postoperative sexual function. In a retrospective of laparoscopic TME (84% LAR and 16% APR), logistic regression identified male patients with tumors greater than 7 cm from the anal verge as much more likely to be capable of erection compared with those with lower tumors, with an odds ratio of 45.5. Anterior or anterolateral tumors in men are likely to affect sexual function more than posterior tumors because of the position of the hypogastric nerves at the level of the prostate.

Tumor stage

Few data exist on the effect of tumor stage on sexual function. In a retrospective analysis, stage was not found to predict sexual function. It could be hypothesized that T4 tumors invading beyond the mesorectal sheath require wider resections, and tumors penetrating the thin anterior mesorectum pose the greatest threat to sexual function, with hypogastric neurovascular bundles coursing through the adjacent Denonvilliers fascia. Although tumor stage was not specified, Hendren and colleagues reported on the sexual function of a cohort of women who underwent en bloc proctectomy with partial or complete vaginectomy. Rates of sexual activity decreased from 48% to 30%, and 39% of patients reported being incapable of sexual activity due to insufficient vaginal capacity, dyspareunia, or chronic perineal wounds. Advanced tumors requiring multivisceral resections place patients at considerable risk for sexual dysfunction. Further research in this area is necessary.

Minimally invasive technique

Existing data on minimally invasive TME are mixed. Early outcomes from the multicenter randomized CLASICC trial suggest greater sexual dysfunction after laparoscopic surgery, with 41% incidence of severely worsened function compared with 26% in the open surgery group. Similarly, in a follow-up of another randomized trial, survivors who were sexually active preoperatively were significantly more likely to be impotent or sexually impaired if they had undergone laparoscopic (40.0%) compared with open surgery (13.6%). Newer data have reached opposing conclusions, however, although from non-randomized studies. Men who underwent laparoscopy demonstrated less dysfunction and better satisfaction at 12 to 18 months and lower rates of postoperative impotence (1/18 patients vs 6/17) compared with men who underwent open procedures ; sexually active women who underwent laparoscopic surgery were also less likely to have reduced function postoperatively (1/14 patients) compared with the open group (5/10 patients). The robotic approach, which is increasingly being used to perform TME, may have benefits over laparoscopic surgery. A recent prospective study comparing laparoscopic and robotic TME found both groups had a deterioration of sexual function at 1 month postoperatively; however, most patients in the robotic group returned to baseline function by 6 months postoperatively, whereas most patients in the laparoscopic group required 12 months to recover function. Patient-reported outcomes from the multicenter randomized COLOR II and ACOSOG Z6051 trials may provide further insight.

TME and non-TME approaches

Prior to the advent of TME, sexual dysfunction after rectal cancer surgery was extremely pervasive, as high as 70% to 100% ; some surgeons considered sexual dysfunction a marker of oncologically adequate resection. TME has resulted in significant improvement in sexual function.

Two other, nonstandard TME approaches have reported data on sexual function. ELND increases the risk to autonomic nerves and has been shown a strong predictor of sexual dysfunction postoperatively, with a decrease in sexual activity from 90% to 50% and in ejaculation from 70% to 10%, when ELND was added to TME. A prospective study from Japan compared male patients undergoing standard TME to patients undergoing TME + ELND, further stratifying them by extent of pelvic nerve preservation, and found that patients in the standard TME group were able to maintain intercourse and nocturnal rigidity at a rate of 95% versus 56%, 45%, and 0% for TME + ELND in patients with bilateral, unilateral, and no nerve preservation, respectively.

Given that local excision of tumors does not impact nerve plexi, transanal techniques could be expected to produce much better sexual outcomes. The literature on this subject is scant, but one prospective study on TEM patients found no change in any sexual item of the EORTC-CR38 when comparing presurgery to 3, 6, and 12 months postsurgery, suggesting that local excision preserves sexual function very well.

LAR versus APR

Several studies comparing LAR to APR have consistently found APR associated with worse sexual function. APR may be associated with more pain from pelvic and perineal scarring and sensory changes as well as possible avulsion of the sphlanchnic nerves from the sacral roots. A meta-analysis of QOL after the two procedures found APR is significantly associated with lower sexual function scores and more male sexual problems. A study of female patients also found decreased activity and a 5.8-fold increase in incidence of dyspareunia with APR. In the bigender cross-sectional study by Hendren and colleagues, patients who underwent LAR had a much higher likelihood (OR 3.5) of being sexually active compared with those who underwent APR. Even for tumors of equal height, function seems worse after APR compared with LAR. There are no studies comparing the sexual function of patients undergoing a hand-sewn coloanal anastomosis to patients undergoing APR. At present, the literature suggests that sexual function is better after LAR than APR.

Ostomy

Separating the impact of an ostomy from the other aspects of APR is difficult, with a dearth of literature to isolate the effects of either colostomy or diverting ileostomy on sexual function. Ostomies seem to have a unique impact on QOL, particularly with respect to body image and feelings of embarrassment that may affect sexual interest or enjoyment in a patient or partner. Thus, ostomies have the potential to profoundly affect sexual function.

Although the true impact of a stoma remains confounded by the consequences of extensive pelvic dissection, there is evidence that sexual function is diminished by more than nerve injury alone. One study reported no significant difference in QOL between patients with and without a stoma but found that stoma patients reported a nonsignificantly lower mean sexual enjoyment (17 vs 67 out of 100) and significantly worse body image. Another found that stoma-related problems were significantly associated with worse QOL, reporting a nonsignificantly lower median score for overall male sexual dysfunction in ostomy patients versus nonostomates (66 and 83, respectively). Other studies have corroborated simultaneous diminishment of sexual and social functions. Issues surrounding body image are prevalent among patients with a stoma.

Radiotherapy

RT is an important component of therapy for many patients with rectal cancer, but it significantly affects postoperative sexual function. RT increases the likelihood that patients describe their sexual life as worsened after treatment by a factor of 5.6. The multicenter Dutch trial, randomizing patients to preoperative RT versus surgery alone, demonstrates significantly worsened overall sexual function in both men and women after neoadjuvant RT, specifically noting greater erectile and ejaculatory dysfunction that continued to deteriorate over time. A population-based Norwegian follow-up of survivors demonstrated significantly diminished erection, orgasm, intercourse, and overall sexual satisfaction, reporting an increase in moderate-to-severe erectile dysfunction by a factor of 7.3 when RT was used. A recent meta-analysis reported significantly worse male sexual function after RT but did not demonstrate clear evidence of worsening of female sexual function. Radiation, however, is known to potentially cause vaginal changes, including shortening, atrophy, fibrosis, adhesions, dryness, dyspareunia, and premature ovarian failure. The effects of timing of RT on sexual function have not been studied, but a retrospective analysis found that both neoadjuvant and adjuvant CRT were predictive of male sexual dysfunction. Pelvic RT has detrimental effects on sexual function.

Chemotherapy

Chemotherapy, especially platinum-based treatment, has a hypothetical risk of causing or exacerbating sexual dysfunction. Further research is needed, but the current literature suggests that chemotherapy does not negatively affect sexual function.