Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer

doi:10.1016/S0140-6736(97)02250-2

The Lancet

Volume 350, Issue 9077, 23 August 1997, Pages 535-540

https://doi.org/10.1016/S0140-6736(97)02250-2 Get rights and content

Summary

Background

Stage Ib and IIa cervical carcinoma can be cured by radical surgery or radiotherapy. These two procedures are equally effective, but differ in associated morbidity and type of complications. In this prospective randomised trial of radiotherapy versus surgery, our aim was to assess the 5-year survival and the rate and pattern of complications and recurrences associated with each treatment.

Methods

Between September, 1986, and December, 1991, 469 women with newly diagnosed stage Ib and IIa cervical carcinoma were referred to our institute. 343 eligible patients were randomised: 172 to surgery and 171 to radical radiotherapy. Adjuvant radiotherapy was delivered after surgery for women with surgical stage pT2b or greater, less than 3 mm of safe cervical stroma, cutthrough, or positive nodes. The primary outcome measures were 5-year survival and the rate of complications. The analysis of survival and recurrence was by intention to treat and analysis of complications was by treatment delivered.

Findings

170 patients in the surgery group and 167 in the radiotherapy group were included in the intention-to-treat analysis; scheduled treatment was delivered to 169 and 158 women, respectively. 62 of 114 women with cervical diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm received adjuvant therapy. After a median follow-up of 87 (range 57–120) months, 5-year overall and disease-free survival were identical in the surgery and radiotherapy groups (83% and 74%, respectively, for both groups). 86 women developed recurrent disease: 42 (25%) in the surgery group and 44 (26%) in the radiotherapy group. Significant factors for survival in univariate and multivariate analyses were: cervical diameter, positive lymphangiography, and adeno-carcinomatous histotype. 48 (28%) surgery-group patients had severe morbidity compared with 19 (12%) radiotherapy-group patients (p=0·0004).

Interpretation

There is no treatment of choice for early-stage cervical carcinoma in terms of overall or disease-free survival. The combination of surgery and radiotherapy has the worst morbidity, especially urological complications. The optimum therapy for each patient should take account of clinical factors such as menopausal status, age, medical illness, histological type, and cervical diameter to yield the best cure with minimum complications.

Introduction

Stage Ib and IIa carcinoma of the cervix can be cured by radical surgery or radiotherapy with similar effectiveness, but the rate and types of complications differ. Radiotherapy is feasible and effective in almost all patients; 5-year survival after this therapy ranges from 78% to 91%.1, 2 By contrast, radical surgery affords the opportunity to study pathological findings, so that groups of at-risk patients who could benefit from adjuvant treatment can be identified. The 5-year cure rate after surgery for early-stage cervical tumours ranges from 54% to 90%; in most cases this rate is achieved with adjuvant therapy.3, 4 The treatment of choice will depend on the policy of the institution, the gynaecologist or radiation oncologist involved, and the age and the general health of the patient.

Apart from Newton's study⁵ about stage-I diseases, there have been no randomised studies to compare radiotherapy with radical surgery in one institution over a short period of time. We conducted a prospective, randomised study to compare external and internal radiotherapy with radical hysterectomy and node dissection. Our main aim was to evaluate 5-year survival and the rate and pattern of complications and recurrences associated with each procedure.

Section snippets

Methods

Between September, 1986, and December, 1991, 578 patients with primary invasive cervical cancer were referred to the Departments of Obstetrics and Gynecology and Radiation Oncology, at the Istituto di Scienze Biomediche S Gerardo, University of Milan, Monza. All patients received standard pretreatment evaluation, which included complete blood analysis, intravenous pyelogram, lymphangiography, cystoscopy, chest radiography, and other tests when indicated. The cervical diameter was assessed by

Results

The trial profile shows the flow of patients in the study (figure 1). Of the 468 patients with FIGO stage Ib or IIa cervical cancer, 125 were excluded because of age (< 30 years, >70 years; n=43), medical illness (n=54), previous or concurrent malignant disease (n=21), or the referring physician's or patient's preference for surgery, radiotherapy, or chemoradiotherapy (n=7).

Thus, 343 patients were randomised: 172 to radical surgery and 171 to radiotherapy. After randomisation, there were six

Discussion

Our review of the published research suggests that cure rates are similar for patients with stage-I cervical cancers who undergo surgery or radiotherapy. Newton⁵ reported that the 5-year survival rate for 119 patients with stage-I disease accrued over 10 years in a partly randomised study was 81% for radical surgery and 74% for radiotherapy; this difference was not significant. Morley and Seski's¹¹ study, of 446 patients with stage-Ib disease recruited between 1945 and 1975 and treated with

References (18)

HL Kottmeier
Complications following radiation therapy in carcinoma of the cervix and their treatment
Am J Obstet Gynecol
(1964)
M Newton
Radical hysterectomy or radiotherapy for stage I cervical cancer
Am J Obstet Gynecol
(1975)
D Chassagne et al.
A glossary for reporting complications of treatment in gynecological cancers
Radiother Oncol
(1993)
GW Morley et al.
Radical pelvic surgery versus radiation therapy for stage I carcinoma of the cervix (exclusive of microinvasion)
Am J Obstet Gynecol
(1976)
R Abad et al.
Clinical significance of adenocarcinoma of the cervix
Am J Obstet Gynecol
(1969)
PW Grigsby et al.
Adenocarcinoma of the uterine cervix: lack of evidence for a poor prognosis
Radiother Oncol
(1988)
DS Kim et al.
Preoperative adjuvant chemotherapy in the treatment of cervical cancer stage Ib, IIa and IIb with bulky tumor
Gynecol Oncol
(1988)
MS Piver et al.
Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (J3 cm) stage Ib cervical carcinoma
Am J Clin Oncol
(1988)
PC Morrow
Is pelvic radiation beneficial in the postoperative management of stage Ib squamous-cell carcinoma of the cervix with pelvic node metastasis treated by radical hysterectomy and pelvic lymphadenectomy?
Gynecol Oncol
(1980)

There are more references available in the full text version of this article.

Cited by (1440)

Comparison of photon energies and field techniques for ovarian dose reduction in volumetric modulated arc therapy
2024, Radiation Physics and Chemistry
For fertility preservation in young female patients undergoing pelvic radiotherapy for cervical cancer, lateral ovarian transposition (LOT) is a procedure that moves the ovaries away from the radiation field. However, it is still challenging to fully protect the ovaries from radiation damage in volumetric modulated arc therapy (VMAT). In this study, we optimized VMAT techniques and simulated the effect of the LOT position on the ovarian dose. Ten cervical cancer patients who received pelvic radiotherapy after LOT were retrospectively analyzed. A restricted arc plus split field technique, which incorporated beam avoidance sectors, split field, fixed jaw, and orthogonal collimator orientation with 10 MV energy (rasf-10MV-VMAT), was designed to minimize the dose to the ovaries. This technique was compared with dual-arc conventional VMAT (dac-6MV-VMAT) and restricted arc and field VMAT (raf-6MV-VMAT) techniques with 6 MV energy. Ovarian dose, target coverage, and organs at risk (OAR) sparing were compared. The location of the ovaries in the anterior-posterior and superior-inferior directions was changed to simulate the effect of the LOT position on the ovarian dose. Compared to dac-6MV-VMAT and raf-6MV-VMAT, rasf-10MV-VMAT decreased the ovarian dose significantly more, especially for a low-dose volume. Both ovaries, received a 44.0–52.1 % lower volume of >3 Gy dose, and (0.5–1.9 Gy) lower maximum and mean doses with rasf-10MV-VMAT (p < 0.05). Rasf-10MV-VMAT also improved target conformity and coverage more than raf-6MV-VMAT (p < 0.05) and reduced the bladder mean dose more than dac-6MV-VMAT (p < 0.05). The ovarian dose decreased with the distance from the target contour, and placing the ovaries near the mid-frontal plane or as high as possible after the LOT lowered ovarian exposure. This technique, using 10 MV photon energy combined with field technique optimization, reduced the ovarian dose, particularly by decreasing the low-dose exposure of ovarian tissue and improving the target conformity simultaneously. The ovarian dose could be minimized by a proper LOT position. This optimized technique could enhance ovarian protection and fertility preservation for young female survivors of cervical cancer.
Systematic Review and Meta-analysis of laparoscopic radical hysterectomy vs. Robotic assisted radical hysterectomy for early stage cervical cancer
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology
Following compelling evidence that open techniques may be related to better survival and disease free survival rates, many gynecologic oncologists in the US have turned away from performing laparoscopic radical hysterectomy (LRH) and robotic radical hysterectomy (RRH) for the treatment of early-stage cervical cancer. While this may be warranted as a safety concern, there is little high-quality data on the head-to-head comparison of LRH and RRH and therefore little evidence to answer the question of where this decrease in patient survival is originating from. In our systematic review, we aimed to compare the complications and outcomes of LRH against those of RRH.
We searched PubMed, Cochrane CENTRAL, Medline, ClinicalTrials.Gov, SCOPUS, and Web of Science from database inception until February 1st, 2022.
A total of 676 studies were identified and screened through a manual three-step process. Ultimately 33 studies were included in our final analysis. We included all studies that compared LRH and RRH and included at least one of our selected outcomes. We included retrospective cohorts, prospective cohorts, case-control, and randomized clinical trials.
Data was independently extracted manually by multiple observers and the analysis was performed using Review Manager Software. PRISMA guidelines were followed. We analyzed homogenous data using a fixed-effects model, while a random-effects model was used for heterogeneous outcomes. We found that following RRH, women had a decreased hospital stay (MD = 0.80[0.38,1.21],(P < 0.002). We found no differences in estimated blood loss (MD = 35.24[-0.40,70.89],(P = 0.05), blood transfusion rate ((OR = 1.32[0.86,2.02],(P = 0.20), rate of post-operative complications (OR = 0.84[0.60,1.17],(P = 0.30), the operative time (MD = 6.01[-4.64,16.66],(P = 0.27), number of resected lymph node (MD = -1.22[-3.28,0.84],(P = 0.25) intraoperative complications (OR = 0.78[0.51,1.19],(P = 0.25), five-year overall survival (OR = 1.37[0.51,3.69],(P = 0.53), lifetime disease free survival (OR = 0.89[0.59,1.32],(P = 0.55), intraoperative and postoperative mortality (within 30 days) (OR = 1.30[0.66,2.54],(P = 0.44), and recurrence (OR = 1.14[0.79,1.64],(P = 0.50).
RRH seems to result in the patient leaving the hospital sooner after surgery. We were unable to find any differences in our ten other outcomes related to complications or efficacy. These findings suggest that the decreased survival seen in minimally invasive RH in previous studies could be due to factors inherent to both LRH and RRH.
CRD42022273727.
High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial
2023, Gynecologic Oncology
Radiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer.
This was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival.
Progression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%).
High-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS.
Clinical trial information: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.
Vulvar cancer survival by primary treatment modality: A retrospective cohort study
2023, Gynecologic Oncology
To compare survival and complications for women with vulvar cancer treated with primary radiation vs surgery.
Retrospective cohort study of Kaiser Permanente members diagnosed with vulvar squamous cell carcinoma (SCC) between 2008 and 2018 and treated with primary surgery (PS only), surgery with adjuvant radiation (PS + RT), or primary radiation (PRT). Primary outcomes were 1- and 3-year overall (OS) and progression-free (PFS) survival. Multivariable regression adjusted for age, stage, comorbidities, and smoking.
We included 201 women: 114 PS only (56.7%), 36 PS + RT (17.9%), and 51 PRT (25.4%). PS only patients had less advanced disease. Crude 1- and 3-year OS were 96.5% and 82.6% for PS only compared to 72.2% and 48.3% for PS + RT and 72.6% and 53.9% for PRT (p < 0.001). There were no statistical differences in hazard of death when controlling for stage and other covariates (PRT vs PS only: aHR 1.35, 95% CI 0.61–2.99; PS + RT vs PS only: aHR 1.28, 95% CI 0.60–2.75; PS + RT vs PRT: aHR 0.95, CI 0.48–1.90). Older age and stage III disease were poor prognostic factors. Risk of lymphedema was elevated with PS + RT (36.1% vs 20.2% for PS only and 9.8% for PRT, p = 0.011). Wound infection was more likely in surgical groups, whereas hospital readmission and blood transfusion were more common with PRT.
Vulvar cancer survival was not statistically different among women treated with primary radiation compared to primary surgery when controlling for stage. Surgery followed by adjuvant radiation demonstrated elevated rates of lymphedema. Primary radiation therapy may be an acceptable alternative to primary surgery in women who are likely to need adjuvant therapy.
A novel predictor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors
2023, Gynecologic Oncology Reports
For early-stage cervical cancer patients experiencing radical surgery, postoperative radiotherapy was recommended for patients with a combination of intermediate-risk factors. However, there was no consensus on whether to administer concurrent chemotherapy. The aim of the study was to confirm the clinical value of the controlling nutritional status (CONUT) score in guiding the use of concurrent chemotherapy during postoperative radiotherapy.
A total of 969 patients with FIGO stage IB-IIA cervical cancer were retrospectively analyzed. Kaplan-Meier survival analysis was performed to compare disease-free survival (DFS) and cancer-specific survival (CSS) rates between different group. A Cox proportional hazards regression test was used to conduct multivariate analyses.
For the patients in the high CONUT group (≥3), the addition of concurrent chemotherapy had better 5-year DFS (91.2 % vs. 72.8 %, P = 0.005) and CSS (93.8 % vs. 77.4 %, P = 0.013) than those without it. Meanwhile, the patients with concurrent chemotherapy had less rate of locoregional recurrence (8.5 % vs 16.7 %, P = 0.034) and distant metastases (11.7 % vs 30.4 %, P = 0.015). The multivariate analysis showed that concurrent chemotherapy was detected to be a factor significantly associated with DFS (P = 0.011), local control (P = 0.041), distant metastasis (P = 0.005) and CSS (P = 0.023). For the patients in low CONUT group (<3), there was no difference in prognosis between patients.
Pretreatment CONUT score may be a predictive factor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors during postoperative radiotherapy, and it can be helpful to determine the adjuvant treatment scheme.
Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study
2023, Gynecologic Oncology
Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival.
This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups.
956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%).
Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029).
Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.

View all citing articles on Scopus

View full text

ArticlesRandomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Am J Obstet Gynecol

Am J Obstet Gynecol

Radiother Oncol

Am J Obstet Gynecol

Am J Obstet Gynecol

Radiother Oncol

Gynecol Oncol

Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (J3 cm) stage Ib cervical carcinoma

Am J Clin Oncol

Is pelvic radiation beneficial in the postoperative management of stage Ib squamous-cell carcinoma of the cervix with pelvic node metastasis treated by radical hysterectomy and pelvic lymphadenectomy?

Gynecol Oncol

Articles
Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer