Conservative Surgery in Early-Stage Cervical Cancer

Vaginal Radical Trachelectomy

A study involving one of the largest series of VRT procedures assessed oncologic, fertility-related, and obstetric outcomes in 125 patients. This series included patients with stages IA, IB, and IIA disease. The median age of the patients was 31 years, and 75% were nulliparous. The majority of the tumors were stage IA2 (21%) or IB1 (69%), and 41% were grade 1. In terms of histology, 56% were squamous and 37% were adenocarcinomas. LVSI was present in 29% of cases, and 88.5% of the lesions measured 2 cm or smaller. The mean follow-up time was 93 months (range, 4–225 months). There were six recurrences (4.8%) and two deaths (1.6%) after VRT. The actuarial 5-year RFS rate was 95.8% (95% confidence interval [CI], 0.90–0.98), whereas it was 79% (95% CI, 0.49–0.93) in the group in which the VRT was abandoned ( P = .001). Higher tumor grade, LVSI, and size greater than 2 cm appeared to be predictive of the risk of abandoning VRT ( P = .001, P = .025, and P = .03, respectively). Tumor size greater than 2 cm was statistically significantly associated with a higher risk of recurrence ( P = .001). The authors concluded that VRT is an oncologically safe procedure in well-selected patients with early-stage disease. Lesion size greater than 2 cm appears to be associated with a higher risk of recurrence and a higher risk of abandoning the planned VRT.

The oncologic safety of VRT was also addressed in a meta-analysis that compared VRT versus radical hysterectomy and included 587 women. The analysis showed that there was no significant difference between the two groups in recurrence rate (hazard ratio [HR] for radical trachelectomy vs. radical hysterectomy, 1.38; 95% CI, 0.58–3.28; P = .47), 5-year RFS rate (HR, 1.17; 95% CI, 0.54–2.53; P = .69), or 5-year overall survival rate (HR, 0.86; 95% CI, 0.30–2.43; P = .78).

Another study evaluated 320 patients with cervical cancer who underwent VRT and aimed to determine the pattern of cancer recurrence in such patients. A total of 10 of the 320 patients had recurrent disease. The recurrence appeared at a mean time of 26.1 months (range, 3–108 months) after VRT. Five patients died within 8.8 months (range, 4–15 months) after recurrence was diagnosed. Two of these five patients had distant metastasis at the time of recurrence. Five patients were treated successfully with surgical intervention, and four patients were treated successfully with chemotherapy. It is interesting to note that none of the patients in that series had high-risk factors.

Abdominal Radical Trachelectomy

In 2013, Pareja and co-workers published a systematic review of the literature concerning patients with early-stage cervical cancer who underwent ART. A total of 485 patients ages 6 to 44 years were identified. The most common stage was IB1 (71%), and the most common histologic subtype was squamous cell carcinoma (70%). Operative times ranged from 110 to 586 minutes. Blood loss ranged from 50 to 5568 mL. Forty-seven patients (10%) had conversion to radical hysterectomy; 155 patients (35%) had a postoperative complication. The most frequent postoperative complication was cervical stenosis (n = 42 [9.5%]). The median follow-up time was 31.6 months (range, 1–124 months). Sixteen patients (3.8%) had disease recurrence. Two patients (0.4%) died of disease. A total of 413 patients (85%) were able to maintain their fertility. A total of 113 patients (38%) attempted to get pregnant, and 67 of them (59.3%) were able to conceive. Therefore the authors concluded that ART is a safe treatment option in patients with early-stage cervical cancer who are interested in preserving fertility.

The relapse rate after ART (3.8%) was similar to the previously reported rate after VRT (4.2%). The death rate after ART (0.4%) was lower than the previously reported rate after VRT (2.9%). However, one must take into account that VRT was performed in earlier years than ART, when the selection criteria were not as strict, and that VRT series included patients at very high risk of recurrence, such as patients with larger tumors and high-risk histologic subtypes.

Minimally Invasive Radical Trachelectomy

Minimally invasive surgical procedures offer patients the advantage of reduced blood loss and transfusion rates, faster return of bowel function, shorter length of hospitalization, and quicker return to daily activities. Over the past several years, the indications for minimally invasive surgery (MIS) have expanded, and advanced radical pelvic surgical procedures are currently frequently performed through either laparoscopy or robotic-assisted techniques.

The first laparoscopic ART procedure was reported by Lee and colleagues in 2003. The largest series to date was described in a study published by Park and co-workers, who reported on 79 patients who underwent laparoscopic radical trachelectomy. The mean age of the patients was 31 years (range, 20–40 years) and the mean tumor size was 1.8 cm (range, 0.4–7 cm). After a median follow-up period of 44 months (range, 3–105 months), nine (11.4%) patients had experienced recurrence and one (1.3%) had died of disease. In that study, the authors showed that a tumor size greater than 2 cm ( P = .039) and a depth of stromal invasion greater than 50% ( P = .016) were significant risk factors for recurrence.

More recently, robotic surgery has enhanced the capabilities of laparoscopic surgery by offering three-dimensional visualization, improved ergonomics, and instrumentation that allows surgeons to increase their dexterity in the surgical field. The safety and feasibility of robotic radical trachelectomy have been previously demonstrated. The robotic approach has been previously compared with the open approach for performance of radical trachelectomy. In a study by Nick and co-workers, the investigators compared 25 patients who underwent open radical trachelectomy and 12 patients who underwent robotic radical trachelectomy. Patients undergoing robotic radical trachelectomy had significantly less blood loss than patients undergoing open radical trachelectomy (median estimated blood loss, 62.5 mL [range, 25–450 mL] vs. 300 mL [range, 50–1100 mL], respectively; P = .0001) and spent fewer postoperative days in the hospital (median length of stay, 1 day [range, 1–2 days] vs. 4 days [range, 3–9 days], respectively; P < .001). There was no difference in operative time between robotic procedures and open procedures (328 minutes [range, 207–379 minutes] vs. 294 minutes [range, 203–392 minutes], respectively; P = .26), and there were no intraoperative complications with either type of procedure.

The largest study published to date comparing open radical trachelectomy and minimally invasive radical trachelectomy (laparoscopic or robotic) evaluated a total of 100 patients. Fifty-eight patients underwent open radical trachelectomy, and 42 patients underwent minimally invasive procedures (laparoscopic or robotic). There were no differences in age, body mass index, race, histology, LVSI, or stage between the two groups ( P > .05). The median surgical time for MIS was 272 minutes (range, 130–441 minutes) and for laparotomy was 270 minutes (range, 150–373 minutes; P = .78). Blood loss was significantly lower for MIS than for laparotomy (50 mL [range, 10–225 mL] vs. 300 mL [50–1100 mL]; P < .0001). Length of hospitalization was shorter for MIS than for laparotomy (1 day [range, 1–3 days] vs. 4 days [range, 1–9 days]; P < .0001). The median lymph node count was 17 (range, 5–47) for MIS vs. 22 (range, 7–48) for open procedures ( P = .03). There were no differences in the rate of postoperative complications (30% for MIS vs. 31% for open surgical procedures). After a median follow-up period of 30 months (range, 0.3–135 months), there was one recurrence in the laparotomy group and none in the MIS group. This patient died of disease.

To date, no data have been published comparing laparoscopic and robotic radical trachelectomy. However, based on retrospective data, it seems that the two approaches are equivalent in terms of perioperative outcomes and oncologic outcomes. There also does not seem to be a compromise in oncologic outcomes when the procedure is performed with a minimally invasive approach compared with the open approach. All patients undergoing radical trachelectomy should be offered the minimally invasive approach if they are deemed appropriate candidates.

Pelvic Lymphadenectomy and Lymphatic Mapping

The risk of pelvic lymph node metastases in patients with stage IA2 to IB1 tumors ranges from 5% to 15%. It is imperative that an evaluation of the pelvic lymph nodes be performed before radical trachelectomy is undertaken. Lymph nodes are removed from the level of the mid–common iliac vessels at the proximal border to the circumflex iliac vein distally, to the psoas muscle with the lateral femoral cutaneous nerve as the most lateral border of the dissection, and medially and inferiorly to the level of the internal iliac vessels and the obturator nerve. In general, if there is evidence of grossly enlarged or suspicious-appearing lymph nodes, these should be sent for frozen section evaluation; if they are determined to be positive for disease, then the procedure should be aborted because these patients are routinely treated with pelvic radiotherapy and chemotherapy.

The role of lymphatic mapping and sentinel nodes is not yet standard in patients with cervical cancer undergoing either radical hysterectomy or radical trachelectomy. A number of prospective studies have shown the safety and feasibility of sentinel node identification and lymphatic mapping in patients with early-stage cervical cancer. (See Chapter 6 .)

Obstetric Outcomes

A number of factors are to be considered when one is interpreting the data on preservation of fertility and the obstetric outcomes in patients undergoing radical trachelectomy. The published literature indicates that not all patients who undergo radical trachelectomy ultimately are able to conceive or even to consider becoming pregnant. The reasons for this vary, given that patients may not prioritize pregnancy immediately after a diagnosis of cancer. Other patients may have been counseled to wait for at least 1 year before attempting to conceive, in order to ensure that there is not an immediate recurrence. Another point to consider is that patients may not have been followed for enough time after radical trachelectomy for pregnancy to be detected, and thus publication of findings may have preceded the pregnancies, leading to a significant underestimation of the true pregnancy rate.

Speiser and co-workers reported their experience with 212 patients who underwent VRT and noted that 76 patients (35.8%) were planning a pregnancy when the data were collected (0–5 years after the procedure). These authors showed that the pregnancy rate for all patients after VRT was 24%. In the unselected population, 85.4% of patients conceive within 12 months if they are trying to conceive. In Speiser’s study, 50 women had a total of 60 pregnancies and 45 live births during the study period. Of the women who were planning to conceive, only those who had already had fertility issues or failed to conceive before trachelectomy had problems afterward. Possible changes that might influence fertility that are potentially caused by the operation itself are reduced cervical mucus; adhesions; reduced blood flow through the uterus, fallopian tubes, and ovaries; and cervical stenosis. Of the 60 pregnancies in the study, five resulted in miscarriage in the first trimester; one woman had an ectopic pregnancy. The rate of first-trimester miscarriages after VRT was lower than the rate in the unselected population (8.4% vs. 14%–20%). In the second trimester, miscarriage was more common (three patients had a late miscarriage), and this rate is comparable with rates in the unselected population (5% after RVT vs. 4% in the general population). There is no suggestion that hormonal treatment to improve fertility alters the oncologic results of VRT.

When considering fertility preservation and success rates after ART, one must take into account that the overall fertility rates are influenced by a number of factors. These include, but are not limited to, a lower overall number of abdominal radical trachelectomies reported in the literature, shorter follow-up time in comparison with published series on VRT, and a potential for greater compromise in blood flow to the uterus, given the larger surgical specimen with the abdominal approach.

In the most comprehensive review of the literature on ART published to date, Pareja and co-workers compiled data on 485 patients who underwent this procedure. They noted that fertility was preserved immediately after ART in the great majority of patients undergoing the procedure: 85%, which was similar to the 91.1% rate of fertility preservation in previously reported series of VRT. In 72 (15%) patients, fertility was not maintained. The reasons were immediate conversion to radical hysterectomy (47 patients), posttrachelectomy radical hysterectomy (6), and postoperative adjuvant radiotherapy and/or chemotherapy (19). Information on pregnancy outcomes was available for 298 patients. A total of 113 (38%) patients attempted to conceive, and 67 of them (59.3%) were successful. Of all patients whose fertility was retained, 67 (16.2%) were able to conceive. There were 18 pregnancy losses (five occurred in the first trimester, nine occurred in the second trimester, and the timing was not reported for the remaining four). Forty-seven deliveries were reported—19 at term, 12 before 36 weeks, and 16 not specified. Of note, there were 10 pregnancies ongoing at the time of the published report. For ART, once patients become pregnant, the rate of successful delivery at term is similar to that previously reported for patients who have undergone VRT (62.6% for ART vs. 68.8% for VRT). The rate of pregnancy loss after ART (24%) appears to be lower than the rate previously reported for VRT (30%), but higher than the rate in the general population (12%).

Data on pregnancy rates and fertility preservation in patients undergoing radical trachelectomy with a minimally invasive approach are limited. In the largest series of laparoscopic radical trachelectomies published to date, Park and co-workers published a report on 79 patients who underwent this procedure. A total of 13 (16.5%) patients were able to conceive. A total of 17 pregnancies were reported in these patients (four missed abortions, seven preterm deliveries, and six full-term deliveries).