Of the 162 patients that underwent rectal surgery in the considered time period, 150 responded to the administered questionnaires (92.6%). 5 other patients were excluded from the study for the following reasons: 1 died within 90 days of surgery, 3 experienced local recurrence during follow up, and 1 had a previous radical cystectomy (Fig. 1). The data regarding the final population of 145 patients are summarized in Table 1.
Table 1
Characteristics of the study population
Variable
|
Coef.
|
95% CI
|
p value
(1 month)
|
p value
(3 months)
|
p value
(6 months)
|
p value
(12 months)
|
Age < 70 years
|
12.7
|
-1.5–26.9
|
0.07
|
0.07
|
0.002
|
0.002
|
BMI > 25
|
1.8
|
-11.4–15.17
|
0.77
|
0.77
|
0.72
|
0.18
|
High vs Medium vs Low rectum
|
12.6
|
-9.38–34.55
|
0.25
|
0.30
|
0.17
|
0.49
|
T3-4 vs T1-2
|
-13.9
|
-32.8–4.96
|
0.14
|
0.22
|
0.12
|
0.11
|
M +
|
-9.9
|
-31.8–11.8
|
0.36
|
0.44
|
0.17
|
0.26
|
Neoadjuvant Therapy
|
7.48
|
-12–26.9
|
0.44
|
0.29
|
0.07
|
0.09
|
Operative Time > 270 min
|
-12.2
|
-35–10.48
|
0.28
|
0.37
|
0.43
|
0.07
|
Transanal Approach
|
18.22
|
-8.2–44.64
|
0.17
|
0.13
|
0.33
|
0.85
|
TME vs PME vs Close-rectal resection
|
-20.7
|
-54.8–13.3
|
0.22
|
0.18
|
0.32
|
0.80
|
Low vs High IMA ligation
|
54
|
8.64–99.36
|
0.02
|
0.01
|
0.06
|
0.06
|
Postoperative complications
|
2.33
|
-25.6–30.3
|
0.86
|
0.75
|
0.19
|
0.63
|
Reintervention
|
6.9
|
-24–38
|
0.65
|
0.94
|
0.45
|
0.67
|
Urinary Retention
|
-27.6
|
-56.2–0.96
|
0.05
|
0.03
|
0.04
|
0.09
|
Pelvic Collection
|
-3.09
|
-27.24–21
|
0.79
|
0.84
|
0.34
|
0.44
|
Anastomotic Stenosis
|
-25.21
|
-58.4–7.95
|
0.13
|
0.13
|
0.38
|
0.36
|
Clavien Dindo ≥ III
|
-19.06
|
-35.8 - -3.34
|
0.01
|
0.03
|
0.02
|
0.005
|
Adjuvant Therapy
|
4.43
|
-9.75–18.6
|
0.53
|
0.47
|
0.54
|
0.33
|
Sphincter-preserving surgery was performed in 136 (93.8%) patients: of these, 34 (25.0%) were rectal resections with PME, 33 (24.3%) were rectal resections with TME, 40 (29.4%) were transanal TME (TaTME) procedures, comprehensive of 7 intersphinteric resection, and 29 (21.3%) were TaMIS proctectomies. The remaining 9 patients (6.2%) underwent abdominoperineal resection according to Miles. Overall postoperative complication rate was 32.4%, while reintervention rate was 17.9%. Adjuvant therapy was required in 55 (37.9%) patients, and 12 patients (8.3%) were treated with adjuvant radiotherapy.
Sexual function
Before surgery, 83.3% of patients reported normal sexual function, while 13.1% patients reported being sexually inactive. The remaining 16.7% presented with preoperative sexual dysfunction. The rate of sexually inactive patients preoperatively was 8.5% in males and 23.5% in females. The mean preoperative IIEF score in males was 61.6 (SD 2.0), while in females the mean preoperative FSFI score was 30.0 (SD 2.0). Changes in postoperative sexual dysfunction rate were not statistically significant when considering males and females as two separate populations (p = 0.12 and p = 0.10 for males and females respectively); however, the trend of variation was significant for the study population as a whole (p = 0.03). Moreover, there was a significant decrease in the dysfunction rate between 1 and 6 months for the entire study population (p = 0.02). The peak of dysfunction rate, in our series, was at 1 month after surgery, reaching 38.1% in males and 37.0% in females. The rate of dysfunction before and after surgery was significantly different (p = 0.04), with an overall increase of 9.3% in sexual dysfunction at 12 months after surgery. Graphs of the dysfunction rate at each time-point are shown in Fig. 2.
Variation of IIEF-15 and FSFI score over time is shown in Fig. 3a and 3b. Score variation over time was statistically significant both in males (p = 0.049) and females (p = 0.036). Multivariate analysis revealed independent predictors of a decrease in IIEF-15 score for males at all time points to be: the onset of urinary retention in the immediate postoperative period, and a Clavien-Dindo score ≥ III (p < 0.05 at all time points, see Table 2). Independent predictors of a higher score were an age of less than 70 years, and a low ligation of the inferior mesenteric artery (p < 0.05, see Table 2).
Table 2
Predictive factors of IIEF-15 score variation in males (multivariate analysis): Age < 70 years and low ligation of IMA were significantly associated with a higher IIEF-15 score. On the contrary, Postoperative Urinary Retention and Clavien Dindo ≥ III were associated with a lower IIEF-15 score.
Variable
|
Coef.
|
95% CI
|
p value
(1 month)
|
p value
(3 months)
|
p value
(6 months)
|
p value
(12 months)
|
Age < 70 years
|
4.06
|
-15.8–23.4
|
0.61
|
0.92
|
0.48
|
0.07
|
BMI > 25
|
0.21
|
-13.1–13.5
|
0.97
|
0.6
|
0.29
|
0.66
|
High vs Medium vs Low rectum
|
16.69
|
-13.4–46.79
|
0.26
|
0.19
|
0.22
|
0.07
|
T3-4 vs T1-2
|
-10.48
|
-26.8–15.09
|
0.19
|
0.22
|
0.08
|
0.09
|
M +
|
-30.58
|
-55.6 - -5.55
|
0.01
|
0.30
|
0.09
|
0.05
|
Neoadjuvant Therapy
|
-7.6
|
-16.88–39.6
|
0.41
|
0.23
|
0.13
|
0.03
|
Operative Time > 270 min
|
1.91
|
-60.12 -63.95
|
0.92
|
0.96
|
0.40
|
0.64
|
Transanal Approach
|
-21.95
|
-83.7–39.86
|
0.34
|
0.59
|
0.14
|
0.72
|
TME vs PME vs Close-rectal resection
|
32.15
|
-60.83–125.1
|
0.35
|
0.85
|
0.43
|
0.55
|
Low vs High IMA ligation
|
-31.12
|
-125.15–60.83
|
0.35
|
0.85
|
0.43
|
0.55
|
Reintervention
|
-30
|
-52.57 - -7.42
|
0.01
|
0.01
|
0.5
|
0.27
|
Urinary Retention
|
-30
|
-52.57 - -7.42
|
0.01
|
0.01
|
0.5
|
0.27
|
Pelvic Collection
|
-36
|
-58.57 - -13.42
|
0.00
|
0.00
|
1.00
|
1.00
|
Anastomotic Stenosis
|
-29.43
|
-39.27 - -19.6
|
0.00
|
0.00
|
0.00
|
0.19
|
Clavien Dindo ≥ III
|
-2.06
|
-22.39–18.26
|
0.83
|
0.28
|
0.40
|
0.27
|
Adjuvant Therapy
|
-4.13
|
-8.18 - -0.09
|
0.56
|
0.73
|
0.76
|
0.04
|
In females, metastatic disease was an independent predictor of a decrease in FSFI score. Among the postoperative factors, the onset of urinary retention, postoperative pelvic collection, reoperation, and anastomotic stenosis were all predictive of a lower FSFI score. No predictors of higher FSFI scores were identified for females. The results of multivariate analysis at each time point are summarized in Table 2 and Table 3. Patients with sexual dysfunction at 1 month postoperatively had a 70% chance of dysfunction which persisted at 6 months.
Table 3
Predictive factors of FSFI score variation in females (multivariate analysis): Metastatic disease, reintervention, postoperative urinary retention, pelvic collection and anastomotic stenosis were significantly associated with a lower FSFI score.
Variable
|
Coef.
|
95% CI
|
p value
(1 month)
|
p value
(3 months)
|
p value
(6 months)
|
p value
(12 months)
|
Age < 70 years
|
-3.75
|
-7.14 - -0.3
|
0.03
|
0.03
|
0.12
|
0.35
|
Female sex
|
-4.25
|
-7.51 - -0.99
|
0.01
|
0.00
|
0.03
|
0.6
|
BMI > 25
|
0.11
|
-3.05–3.28
|
0.94
|
0.89
|
0.89
|
0.09
|
High vs Medium vs Low rectum
|
-2.16
|
-7.47–3.13
|
0.41
|
0.30
|
0.16
|
0.30
|
T3-4 vs T1-2
|
4.33
|
0.00–8.67
|
0.05
|
0.11
|
0.21
|
0.78
|
Neoadjuvant Therapy
|
0.72
|
-2.7- 4.16
|
0.65
|
0.79
|
0.63
|
0.67
|
Operative time > 270 min
|
1.44
|
-3.58–6.46
|
0.56
|
0.65
|
0.89
|
0.20
|
Transanal Approach
|
-6
|
-12.29–0.28
|
0.04
|
0.05
|
0.9
|
0.5
|
TME vs PME vs Close-rectal resection
|
2.59
|
-5.58–10.77
|
0.52
|
0.36
|
0.29
|
0.24
|
Low vs High Arterial Ligation
|
-6.95
|
-18.91–5
|
0.24
|
0.11
|
0.34
|
0.36
|
Complications
|
4.05
|
-1.33–9.44
|
0.13
|
0.63
|
0.54
|
0.25
|
Reintervention
|
0.54
|
-5.29 -6.38
|
0.85
|
0.79
|
0.76
|
0.47
|
Urinary Retention
|
14.21
|
8.49–19.94
|
0.00
|
0.00
|
0.00
|
0.10
|
Pelvic Collection
|
0.15
|
-5.29–6.38
|
0.95
|
0.66
|
0.47
|
0.52
|
Clavien Dindo ≥ III
|
2.48
|
-0.40–5.36
|
0.06
|
0.05
|
0.87
|
0.13
|
Adjuvant Therapy
|
-1.11
|
-3.93–1.71
|
0.43
|
0.65
|
0.48
|
0.42
|
Urinary function
Before surgery, 93.8% of patients had normal urinary function. Among patients with preoperative dysfunction, the majority (88.9%) reported only mild dysfunction. The trend of urinary dysfunction rate over time is shown in Fig. 4. Dysfunction rate before and after surgery is significantly different in males, with an increase of 10% at 12 months postoperatively (p = 0.002). The decrease in urinary dysfunction rate was significant in males between 1 and 6 months (p = 0.04), while it was insignificant in females (p = 0.68). Figure 5 shows significant variation of IPSS scores over time for the overall population (p = 0.03). Being male, and the onset of postoperative urinary retention, were independent predictors of a higher IPSS score, while an age of less than 70 years, and having undergone surgery with transanal approach were independent predictors of a lower IPSS score. The results of the multivariate analysis for urinary dysfunction are reported in Table 4. For patients with urinary dysfunction at 1 month, the risk of continued dysfunction at 6 months was 62%.
Table 4
Predictive factors of IPSS score variation in the whole study population (multivariate analysis): Age < 70 years, female sex and transanal approach were associated with a lower IPSS score. Postoperative urinary retention was associated with a higher IPSS score.
Variable
|
Coef.
|
95% CI
|
p value
(1 month)
|
p value
(3 months)
|
p value
(6 months)
|
p value
(12 months)
|
Age < 70 anni
|
3.58
|
-3.88–11.05
|
0.34
|
0.13
|
0.08
|
0.41
|
BMI > 25
|
-1.31
|
-7.14–4.05
|
0.65
|
0.80
|
0.82
|
0.43
|
High vs Medium vs Low rectum
|
-20.10
|
-30.58 – − 9.62
|
0.00
|
0.00
|
0.00
|
0.05
|
T3-4 vs T1-2
|
0.44
|
-7.67–8.56
|
0.91
|
0.97
|
0.84
|
0.23
|
Neoadjuvant Therapy
|
-3.01
|
-12.96–6.94
|
0.54
|
0.62
|
0.74
|
0.95
|
Operative Time > 270 min
|
4.3
|
-4.73–13.35
|
0.34
|
0.58
|
0.50
|
0.85
|
Transanal Approach
|
12.61
|
1.64–23.57
|
0.025
|
0.008
|
0.035
|
0.21
|
TME vs PME vs Close-rectal resection
|
0.65
|
-14.41–15.73
|
0.09
|
0.88
|
0.92
|
0.50
|
Loop ileostomy closure > 90 days
|
0.59
|
-6.56–7.74
|
0.90
|
0.94
|
0.86
|
0.95
|
Postoperative complications
|
0.72
|
-9.69–11.13
|
0.89
|
0.64
|
0.68
|
0.43
|
Reintervention
|
-3.03
|
-19.47–13.04
|
0.71
|
0.80
|
0.87
|
0.45
|
Pelvic collection
|
1.82
|
-7.94–11.6
|
0.71
|
0.49
|
0.47
|
0.95
|
Anastomotic Stenosis
|
17.22
|
5.47–28.97
|
0.00
|
0.00
|
0.00
|
0.01
|
Clavien Dindo ≥ III
|
6.86
|
-2.19–15.92
|
0.03
|
0.06
|
0.11
|
0.56
|
Adjuvant Therapy
|
-5.22
|
-10.72–0.27
|
0.06
|
0.04
|
0.19
|
0.07
|
Intestinal function
The rate of patients with LARS-like symptoms in the preoperative period was 15.2% with 8.3% having severe symptoms. In our study population, half of these patients received a definitive stoma. The postoperative trend of intestinal dysfunction rate was not statistically significant (p = 0.07). As reported in Fig. 6, there was a significant increase (p = 0.005) between the preoperative and 12-month LARS rate in the whole study population. A transanal surgical approach, and the onset of high-grade complications (Clavien-Dindo score ≥ III) were independent predictors of postoperative LARS-like symptoms. The presence of anastomotic stenosis was also a predictor of the development of intestinal dysfunction at all time points. Regarding continence, the presence of pelvic collection or postoperative anastomotic stenosis were predictors of postoperative incontinence. The results of the multivariate analysis for intestinal dysfunction at all time points are shown in Table 5. Patients with LARS-like symptoms at 1 month had a 92% chance of symptoms persisting at 6 months. Patients treated with postoperative pelvic floor rehabilitation had a LARS score at all time points that was higher by 18, 17, 15 and 10 points at 1, 3, 6 and 12 months; however, the decrease in LARS score at each time point among these patients is statistically significant (p < 0.001).
Latent Class Analysis
LCA allowed us to distinguish two classes for each type of dysfunction. Tables 6a, 6b and 6c show estimated predicted probabilities with 95% Cis. The considered variables allowed the identification of two phenotypes: one with lower risk of developing dysfunction, denoted as the “low risk” class, and another with characteristics that are associated with a higher risk of developing dysfunction, denoted as the “high risk” class. Regarding sexual dysfunction, the high risk class was defined by surgery with a transabdominal approach and no confection of loop-ileostomy. No difference was found regarding complication rates between the two classes. Considering urinary dysfunction, a Clavien-Dindo score ≥ III, and the presence of pelvic collection, defined the high risk class. The high risk class in intestinal dysfunction was instead characterized by surgery that used a transanal approach, and a low anastomosis site.
Table 5. Predictive factors of LARS score variation in the whole study population (multivariate analysis): Pathologies of the higher rectum were associated with a lower LARS score. Transanal approach, anastomotic stenosis and Clavien-Dindo ≥ III were instead associated with a higher LARS score.
Variable
|
Coef.
|
95% CI
|
p value
(1 month)
|
p value
(3 months)
|
p value
(6 months)
|
p value
(12 months)
|
Age < 70 anni
|
3.58
|
-3.88 – 11.05
|
0.34
|
0.13
|
0.08
|
0.41
|
BMI > 25
|
-1.31
|
-7.14 - 4.05
|
0.65
|
0.80
|
0.82
|
0.43
|
High vs Medium vs Low rectum
|
-20.10
|
-30.58 – - 9.62
|
0.00
|
0.00
|
0.00
|
0.05
|
T3-4 vs T1-2
|
0.44
|
-7.67 – 8.56
|
0.91
|
0.97
|
0.84
|
0.23
|
Neoadjuvant Therapy
|
-3.01
|
-12.96 – 6.94
|
0.54
|
0.62
|
0.74
|
0.95
|
Operative Time > 270 min
|
4.3
|
-4.73 – 13.35
|
0.34
|
0.58
|
0.50
|
0.85
|
Transanal Approach
|
12.61
|
1.64 – 23.57
|
0.025
|
0.008
|
0.035
|
0.21
|
TME vs PME vs Close-rectal resection
|
0.65
|
-14.41 – 15.73
|
0.09
|
0.88
|
0.92
|
0.50
|
Loop ileostomy closure > 90 days
|
0.59
|
-6.56 – 7.74
|
0.90
|
0.94
|
0.86
|
0.95
|
Postoperative complications
|
0.72
|
-9.69 – 11.13
|
0.89
|
0.64
|
0.68
|
0.43
|
Reintervention
|
-3.03
|
-19.47 – 13.04
|
0.71
|
0.80
|
0.87
|
0.45
|
Pelvic collection
|
1.82
|
-7.94 – 11.6
|
0.71
|
0.49
|
0.47
|
0.95
|
Anastomotic Stenosis
|
17.22
|
5.47 – 28.97
|
0.00
|
0.00
|
0.00
|
0.01
|
Clavien Dindo ≥ III
|
6.86
|
-2.19 – 15.92
|
0.03
|
0.06
|
0.11
|
0.56
|
Adjuvant Therapy
|
-5.22
|
-10.72 – 0.27
|
0.06
|
0.04
|
0.19
|
0.07
|
Table 6a. LCA sexual dysfunction
Latent Class
|
1 (low risk)
|
2 (high risk)
|
Marginal probability (%)
|
40%
|
60%
|
Variables (95% CI)
|
Neoadjuvant therapy
|
0.64 (0.43-0.80)
|
0.27 (0.18-0.39)
|
Transanal surgery
|
0.76 (0.42-0.93)
|
0.28 (0.19-0.39)
|
Loop ileostomy
|
0.99 (0-1)
|
0.19 (0.04-0.59)
|
Complications
|
0.32 (0.9-0.49)
|
0.32 (0.21-0.45)
|
6-m Sexual dysfunction
|
0.19 (0.09-0.35)
|
0.32 (0.22-0.45)
|
Table 6b. LCA urinary dysfunction
Latent Class
|
1 (low risk)
|
2 (high risk)
|
Marginal probability (%)
|
83%
|
17%
|
Variables
(95% CI)
|
Transanal surgery
|
0.49 (0.39-0.58)
|
0.41 (0.22-0.62)
|
Pelvic collection
|
0.02 (0.00-0.99)
|
0.99 (0-1)
|
Cl. Dindo ≥ III
|
0.12 (0.07-0.19)
|
0.75 (0.10-0.98)
|
6-m Urinary dysfunction
|
0.18 (0.12-0.25)
|
0.35 (0.14-0.63)
|
Table 6c. LCA intestinal dysfunction
Latent Class
|
1 (low risk)
|
2 (high risk)
|
Marginal probability (%)
|
37%
|
63%
|
Variables
(95%CI)
|
Transanal surgery
|
0.00 (0-1)
|
0.75 (0.63-0.84)
|
Loop ileostomy
|
0.13 (0.05-0.27)
|
0.74 (0.63-0.82)
|
Anastomosis ≤ 5 cm
|
0.09 (0.01-0.45)
|
0.98 (0.89-0.99)
|
Complications
|
0.34 (0.22-0.48)
|
0.31 (0.22-0.42)
|
6-m Intestinal dysfunction
|
0.03 (0.00-0.21)
|
0.57 (0.44-0.68)
|
Quality of life
Quality of life was assessed at the last follow up using the EORTC-QLQC30 questionnaire revealing a mean score of 93.25 (SD 8.4) points. After dividing the study population into two groups of patients, one with a follow up < 12 months and the other with a follow up ≥ 12 months, there was no significant difference in quality of life scores apparent between the two groups, respectively 93.36 (SD 9.85) points for follow up < 12 months and 93.23 (SD 8.13) points for follow up ≥ 12 months (p = 0.58). For patients with sexual dysfunction, the mean quality of life score was 90.8 (SD 9.54). Patients with urinary dysfunction alone had a mean score of 88.8 (SD = 10.52), and patients experiencing LARS and incontinence had a mean score of 81 (SD = 7.57). Only 5 patients reported all three forms of dysfunction simultaneously, having a mean quality of life score of 76.6 (SD 6.95).