The sites of recurrences were the pelvis in 21 patients, lung in 11 patients, liver in 5 patients, and lymph nodes in 10 patients.
Of the 271 patients, 68 (25%) experienced at least 1 complication, whereas 203 (75%) patients were free from complications. Table 1 describes the features of patients who experienced at least 1 complication and features of patients with any complications; any statistically relevant difference was observed in the 2 groups for age, stage, histologic diagnosis, grade, type of surgery, and surgical approach.
We found 87 complications in 68 patients; 53 patients developed 1 complication, 15 patients developed 2 complications, and 1 patient developed 4 complications.
Most of the complications observed were mild (G1; 63.2%), 34.5% were moderate (G2), and 2.3% were severe (G3) (Table 2). We had no fatal complication (G4).
Most of the complications were found in the urinary system (30%) and in the cutaneous system (30%; Table 2). Fewer complications were found in the vascular system (16%), in the gastrointestinal system (9.1%), in genital sites (9.2%), in pelvic soft tissue (2.3%), in the nervous system (2.3%), and in the hematopoietic system (1.1%).
Urinary complications were cystocele (6/87 total complications), stress incontinence (12/87) postoperative ureterovaginal fistula with subsequent adequate renal function after treatment not requiring surgery (2/87), ureterovaginal fistula requiring surgery with subsequent inadequate renal function (1/87), any immediate symptoms of cystitis lasting more than 2 weeks after the completion of treatment (1/87), any symptoms or signs of abnormal bladder functions with residual volume of 100 mL or more (1/87), and postural incontinence (3/87).
Cutaneous complications were mostly surgical wound infection and dehiscence not requiring surgery (12/87) or requiring surgery (12/87).
Vascular complications were mostly permanent or intermittent leg edema not interfering (4/87) or interfering (5/87) with normal activity.
Three patients developed a rectocele not requiring treatment, and 1 woman developed a sigmoid fistula.
Genital site complications were 6 vaginal narrowing and shortening to half or less than half the original dimensions and 2 vaginal narrowing and shortening to more than half the original dimensions.
Patients who experienced at least 1 complication had been treated with surgery alone (10/68 [14.7%]), surgery + RT (32/68 [47%]), surgery + RT + CT (18/68 [26.4%]), surgery + CT (3/68 [4.4%]), RT alone (6/68 [8.8%]), no CT alone, and no CT + RT.
Patients who experienced 2 complications had been treated with surgery alone (8/15), surgery + RT (4/15), or surgery + CT (3/15). One patient experienced 4 complications after surgery alone.
Severe complications were developed by 1 patient treated with surgery alone (sigmoid fistula) and by 1 patient treated with surgery + RT (ureterovaginal fistula requiring surgery with subsequent inadequate renal function).
In the group of patients laparoscopically treated, there were 26 complications (26/59 [44%]) including 8 complications in the urinary tract (8/59 [13.5%]; 2 patients with cystocele, 4 patients with stress incontinence, 1 patient with postural incontinence, and 1 patient with ureterovaginal fistula requiring surgery with subsequent inadequate renal function), 6 complications in the vascular system (6/59 [10%]; 3 patients with leg edema interfering and 3 patients with leg edema not interfering with normal activity), 4 complications in the gastrointestinal system (4/59 [7%]; 2 patients with rectocele, 1 patient with intermittent periods of diarrhea and constipation, and 1 patient with sigmoid fistula), 3 complications in the genital tract (3/59 [5%]), 2 complications in the cutaneous system (2/59 [3%]), 2 complications in the nervous system (that correspond to 100% of nerve injuries; 2/59 [3%]), and 1 hematopoietic complication (1/59 [1.7%]) (Table 3).
In this subgroup of patients, 15 (57.7%) complications were G1, 9 (34.6%) complications were G2, and 2 (7.7%) complications were G3; these were the only 2 G3 complications in the whole group of patients.
Among the patients laparotomically treated, there were 61 (30.5%) complications. Most of these were cutaneous (24/200 [12%]) or urinary (18/200 [9%]) and G1 (40/200 [20%]) with no G3 complications.
The incidence of complications in the group of patients treated with laparoscopy or laparotomy was statistically different only for cutaneous complications to the detriment of the laparotomy group (P = 0.018).
In the group of patients who underwent pelvic lymphadenectomy, there were 37 complications (37/113 [32.7%]), with 9 (8%) of the 113 patients having vascular complications including lymphocele (Table 4). In this subgroup of patients, 20 (18%) complications were G1, 15 (13%) complications were G2, and 2 (2%) complications were G3.
In the group of patients who did not undergo lymphadenectomy, there were 50 complications (50/146 [34.2%]) including 5 (3.5%) of the 146 patients with vascular complications. All complications were G1 (35/50 [70%]) and G2 (30%) with no G3 complications.
The incidence of complications in the group of patients treated or not with lymphadenectomy was not statistically different (P = 0.088).
The most frequent complications in patients who were submitted to surgery alone were cutaneous (18 cutaneous complications/47 total complications). All other complications were diagnosed in patients who were submitted to an integrated treatment; most frequent complications in patients who were submitted to surgery + RT/surgery + CT/surgery + RT + CT were urinary (7/24 patients), vascular (4/10 patients), and both cutaneous (2/6 patients) and vascular (2/6 patients), respectively (Table 5).
We observed any statistically significant association of a specific system complication in relation to a RT treatment or a CT treatment (P = 0.187).
Any statistically significant difference was seen in the incidence of at least 1 complication in women treated with surgery alone (36/135 [26.6%] women) and in patients who were submitted to an integrated treatment (considering surgery + RT/surgery + CT/surgery + RT + CT, all together; 32/136 [23.5%] women; P = 0.19). Patients who were submitted to both surgery and RT show a trend of higher rate of at least 1 complication (19/58 [32.7%] patients) if compared with surgery alone (26.6%), even if the difference is not statistically significant (P = 0.09).
A figure showing the relationship between time of onset of complications and different systems is given (Fig. 4). In the urinary system, 50% of the complications occurred within 30 months after treatment, but some of them occurred even after 5 years. A total of 50% of the complications occurred in the cutaneous system (uterus, vagina, and vulva tissues and pelvic soft tissues) within 12 months after treatment, within 5 months in the gastrointestinal system, within 4 months in the vascular system, and within 1 month in peripheral nerves.
In general, 44 (50%) complications appeared within 1 year after treatment, but 9 (10%) complications appeared after 60 months of follow-up (5 urinary, 2 cutaneous, 1 genital, and 1 vascular complications). The glossary included all observed complications.
The treatment of endometrial carcinoma is primarily surgical with Querleu-Morrow type A radical hysterectomy and bilateral salpingo-oophorectomy, and this can be accomplished via laparotomy or via laparoscopy, vaginally or robotically.
Three recent large prospective randomized controlled trials from Holland, Australia, and the United States have been published comparing laparotomy and laparoscopy in endometrial cancer.28–30 Focusing on complications, similar rates of surgical complications were reported for the 2 approaches in the Dutch study—14.6% for laparoscopy and 14.9% for laparotomy. The Australian and American studies instead reported similar rates of intraoperative complications (5.6% for laparotomy and 7.4% for laparoscopy), but postoperatively, twice as many laparotomy patients had severe adverse events prevailing wound infection (10%), ileus (8%), and cardiac complications (2%).
In our series, the rate of complications in patients who were submitted to surgery alone was not statistically different for laparoscopy and laparotomy, with 31% of complications for laparoscopy and 24.7% for laparotomy (P = 0.449). Our data confirm the prevalence of cutaneous issues in laparotomic patients (P = 0.018), whereas gastrointestinal and cardiovascular complications were not statistically different in the 2 groups.
Surgical staging with pelvic and para-aortic lymph nodes dissection may be added to hysterectomy. The role of lymphadenectomy and its extent remains, however, controversial with available randomized trials showing any advantage in survival at least in low-risk patients but increased rates of complications.31–39
Benedetti Panici et al32 assessed that both early and late postoperative complications occurred more frequently in patients who were submitted to lymphadenectomy if compared with hysterectomy alone,32 and this trend was confirmed in the MRC ASTEC trial with ileus occurring in 3% of patients versus 1%, deep vein thrombosis in 1% versus 0.1%, lymphocyst in 1% versus 0.3%, and major wound dehiscence in 1% versus 0.3%.31
In the recent article from Dowdy et al,40 pelvic and para-aortic lymphadenectomy was a statistically significant predictor of severe morbidity (OR 2.3 compared with no lymphadenectomy) and increased costs.
Our data do not confirm the higher prevalence of complications in patients who were submitted to lymphadenectomy (even if both G3 complications occurred in the lymphadenectomy group); the extent of the nodes dissection was at the discretion of the surgeon, and para-aortic lymphadenectomy up to the renal vessels was added to pelvic dissection in 25% of cases (28 patients/113 lymphadenectomy).
The median number of removed pelvic nodes was 18 (26 pelvic nodes in Benedetti Panici trial32), and this can partially explain our low rate of complications in patients who were submitted to lymphadenectomy.
Intermediate-risk patients may undergo adjuvant vaginal brachytherapy after surgery, whereas patients with high-risk endometrial cancer benefit from the concurrent and/or sequential use of CT and external beam irradiation with or without brachytherapy.41
PORTEC 1 trial showed that the combination of surgery and RT increases the complication rates if compared with surgery alone (25% vs 6%, P < 0.0001).42,43
In our series, patients who were submitted to both surgery and RT show a trend of higher rate of at least 1 complication (19/58 [32%] patients) if compared with surgery alone (36/135 [27%] patients), even if the difference was not statistically significant (P = 0.09).
Even considering all patients who were submitted to integrated treatments, our data do not show a significant difference in the rate of at least 1 complication when compared with women who underwent surgery alone (23.5% vs 26.6%, P = 0.19).
A possible explanation of this incongruence between literature and our data is that in our series, only 30 women underwent an integrated treatment with surgery, RT and CT, that is the heaviest therapy for these patients. Another reason for this discrepancy may be that often, the heaviest complications obscure other minor complications, thus suggesting a possible bias in the collection of complications after integrated therapies.
The interesting data from our study were the possibility of diagnosing a complication even after 5 years after the end of the treatment; therefore, every gynecologist involved in the follow-up of endometrial cancer should check for late complications, especially in the urinary and cutaneous systems.
The prospective collection of the data and a median follow-up of more than 3 years were the strengths of our study, whereas the monocentric nature of the study and, above all, the lack of data about the influence of complications on quality of life and sexuality were our limitations, being these issues of primary importance in the every day life of these long-surviving women. The glossary has been sufficiently comprehensive to describe all complications in our study.
The treatment of patients with endometrial cancer is mainly surgical with a relatively small number of complications. Surgical teams should be very careful in the abdomen closure because laparocele and wound infection are still frequent complications especially after laparotomic approach. Additional therapies should be carefully weighted to limit complications from integrated therapies. Monitoring these complications is fundamental in modern oncology, even in the long term, and the French-Italian glossary proved to be a comprehensive clinical instrument in this setting, regardless of the type of therapy delivered.
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Keywords:© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.
Complications; Endometrial cancer; Radiotherapy; Surgery; Chemotherapy