Lack of effect of tumor size on the prognosis of carcinoma of the uterine cervix Stage IB and IIA treated with preoperative irradiation and surgery.
ABSTRACT The purpose of this analysis was to evaluate the prognostic significance of cervical tumor size in patients with Stages Ib and IIa carcinoma of the cervix treated with preoperative irradiation and radical or conservative hysterectomy.
This study is a retrospective analysis of 177 patients. One hundred forty-one patients had Stage Ib and 36 patients had Stage IIa carcinoma of the cervix. All patients were treated with preoperative irradiation and surgery. Radiation therapy consisted of external pelvic irradiation and intracavitary brachytherapy; total doses ranged from 30 to 60 Gy to the pelvic sidewall and 60 to 70 Gy to point A. Surgery consisting of radical hysterectomy and lymph node dissection or a conservative hysterectomy and lymph node dissection was performed 4 to 6 weeks after completion of irradiation.
The 5-year progression-free survivals were 80% for Stage Ib and 63% for Stage IIa (p = 0.03). The 5-year cumulative pelvic failure rates for Stage Ib were 16% for tumors <3 cm and 9% for tumors >3 cm (p = 0.90). The 5-year cumulative pelvic failure rates for Stage IIa were 22% for tumors <3 cm and 22% for tumors >3 cm (p = 0.75). The corresponding cumulative distant metastasis failure rates at 5 years for Stage Ib were 21% for tumors <3 cm and 21% for tumors >3 cm (p = 0.60). For patients with Stage IIa disease, the 5-year cumulative distant metastasis rates were 33% for tumors <3 cm and 36% for tumors >3 cm (p = 0.70). A multivariate analysis was performed to evaluate prognostic factors for the endpoint of progression-free survival. The variables that were analyzed were patient age, tumor histology, tumor size, clinical stage, point A and pelvic lymph node irradiation dose, and cervical tumor status and pelvic lymph node status at the time of hysterectomy. The variables that were found to be of independent significance for progression-free survival by multivariate analysis were pelvic lymph node irradiation dose (p <0.001), pelvic lymph node status at the time of hysterectomy (p = 0.01), and clinical stage (p = 0.02). Cervical tumor size at the time of diagnosis and the presence of tumor cells in the cervix in the hysterectomy specimen was not an independent prognostic factor by multivariate analysis. The overall severe complication rate was 11% for all patients.
For this population of patients treated with preoperative irradiation and surgery, pelvic lymph node status at the time of hysterectomy and the preoperative irradiation dose to the pelvic lymph nodes are independent predictors of progression-free survival and the development of distant metastasis. The pretreatment cervical tumor size is of less importance for predicting progression-free survival and the development of distant metastasis but clinical stage is an important prognostic variable. These results are in contrast with those of surgery or irradiation alone, in which primary tumor size is a critical prognostic factor for all outcome parameters.
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ABSTRACT: Purpose. – To identify prognostic factors and treatment toxicity in a series of operable stages IB and II cervical carcinomas.Patients and methods. – Between May 1972 and January 1994, 414 patients (pts) with cervical carcinoma staged according to the 1995 FIGO staging system underwent radical hysterectomy with (n=380) or without (n=34) bilateral pelvic lymph node dissection. Lateral ovarian transposition to preserve ovarian function was performed on 12 pts. The methods of radiation therapy (RT) were not randomised and depended on the usual practices of the surgical teams. Group I: 168 pts received postoperative RT (64 pts received vaginal brachytherapy alone 〚mean total dose (MD): 50 Gy〛, 93 pts had external beam pelvis RT (EBPRT) 〚MD: 45 Gy over 5 weeks〛 followed by vaginal brachytherapy 〚MD: 20 Gy〛, and 11 pts had EBPRT alone 〚MD: 50 Gy over 6 weeks〛. Group II: 246 pts received preoperative utero-vaginal brachytherapy 〚MD: 65 Gy〛, and 32 of theses 246 pts also received postoperative EBPRT 〚MD: 45 Gy over 5 weeks〛 delivered to the parametric and the pelvic lymph nodes with a midline pelvic shield. The mean follow-up was 106 months.Results. – The 10-year disease-free survival (DFS) rate was 80%. From 75 recurrences, 35 were isolated locoregional. Multivariate analysis showed that independent factors decreasing the probability of DFS were: both exo and endocervical tumour site (p=0.047), lymph-vascular space invasion (p=0.041), age ≤ 51 yr (p=0.013), 1995 FIGO staging system (stage IB1 vs stage IIA, p=0.004, stage IB1 vs stage IB2, p=0.0009, and stage IB1 vs stage IIB with 1/3 proximal parametrical infiltration, p=0.00002), and histological pelvic involved lymph nodes (p=0.00009). Methods of adjuvant RT did not influence the probability of DFS (group I vs group II, p=0.10). The postoperative complication rate was 10.2% in group I and 8.9% in group II (p=0.7) but the postoperative urethral complication rate necessitating surgical intervention with reimplantation was lower in group I than in group II (0.6% vs 2.3%, respectively, p=0.03). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 10.4%. EPRT significantly increased the 10-year rate for grade 3 and 4 late radiation complications (yes vs no: 22% vs 7%, respectively, p=0.0002).Conclusion. – In our series, the methods of adjuvant RT (primary surgery vs preoperative uterovaginal brachytherapy) do not seem to influence the prognosis of the stage IB, IIA, and IIB (with 1/3 proximal parametrical involvement only) cervical carcinomas. The postoperative EPRT applied according to histopathological risk factors after surgical treatment increases the risk of late radiation complications.Cancer/Radiothérapie 06/2002; 6(4):217-237. · 1.11 Impact Factor
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ABSTRACT: Purpose. – To identify prognostic factors and treatment toxicity in a series of operable bulky stages I and II cervical carcinomas treated with a therapeutic modality combining primary irradiation and surgery.Patients and methods. – Between July 1982 and May 1996, 66 patients with bulky squamous-cell cervical carcinomas (stages IB2, IIA, and IIB with 1/3 proximal parametrial invasion) underwent primary external beam pelvic radiation therapy (37.40 Gy to 40 Gy over 4.5 weeks) and low-dose-rate uterovaginal brachytherapy (20 Gy) followed, 5 to 6 weeks later, by class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. The four last patients received concomitant chemotherapy during the first and the fourth radiation week combining 5-FU and cisplatin. A clinical pelvic lymph node involvement had been observed in 7 patients. The clinical median tumor size was 5 cm in diameter (range: 4.5-8 cm). The median follow-up was 97 months.Results. – Pathologic complete tumor response in specimen of hysterectomy were observed in 46 patients. Six patients had pathologic unilateral iliac lymph node involvement. The 5- and 10-year specific survival rates were 79 and 74%, respectively. The 5- and 10-year disease-free survival rates were 76% and 71%, respectively. The 10-year local control rate was 85%. The 10-year probability for pelvic recurrence was significantly influenced by the pathologic tumor response: 26% in the residual group vs 5% in the complete tumor response group, P=0.024). After multivariate analysis, the independent factors decreasing the probability of disease-free survival were: pathologic pelvic lymph node involvement (P=0.029), and parametrial invasion (P=0.031). Five late severe complications recquiring surgical intervention were observed: 2 bowell obstructions, 1 ureteral stenosis, 1 vesicovaginal fistula, and 1 radiation induced unilateral femoral necrosis.Conclusion. – A good local control is obtained after combined primary radiation therapy and surgery for bulky stages I and II cervical carcinomas. In our more recent practice, the treatment combines primary concomitant chemoradiation followed by surgery including pelvic and para-aortic lymphadenectomy.Cancer/Radiothérapie 04/2002; 6(2):85-98. · 1.11 Impact Factor
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ABSTRACT: Purpose. – To evaluate preliminary results in terms of toxicity, local tumour control, and survival after preoperative concomitant chemoradiation for operable bulky cervical carcinomas.Patients and methods. – Between December 1991 and October 2001, 42 patients (pts) with bulky cervical carcinomas stage IB2 (11 pts), IIA (15 pts), and IIB (16 pts) with 1/3 proximal parametrial invasion. Median age was 45 years (range: 24–75 years) and clinical median cervical tumour size was 5 cm (range: 4.1–8 cm). A clinical pelvic lymph node involvement has been observed in 10 pts. All patients underwent preoperative external beam pelvic radiation therapy (EBPRT) and concomitant chemotherapy during the first and the fourth radiation weeks combining 5-fluorouracil and cisplatin. The pelvic dose was 40.50 Gy over 4.5 weeks. EBPRT was followed by low-dose-rate uterovaginal brachytherapy with a total dose of 20 Gy in 17 pts. After a rest period of 5–6 weeks, all pts underwent class II modified radical hysterectomy with bilateral lymphadenectomy. Para-aortic lymphadenectomy was performed in eight pts without pathologic para-aortic lymph node involvement. Twenty-one of 25 pts who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy of 20 Gy. The median follow-up was 31 months (range: 3–123 months).Results. – Pathologic residual tumour or lymph node involvement was observed in 23 pts. Among the 22 pts with pathologic residual cervical tumour (1 cm: 10 pts), seven underwent preoperative EBRT followed by uterovaginal brachytherapy vs. 15 treated with preoperative EBRT alone (P = 0.23). Four pts had pathologic lymph node involvement, three pts had vaginal residual tumour, and four pts had pathologic parametrial invasion. The 2- and 5-year overall survival rates were 85% and 74%, respectively. The 2- and 5-year disease-free survival (DFS) rates were 80% and 71%, respectively. After multivariate analysis, the pathologic residual cervical tumour size was the single independent factor decreasing the probability of DFS (P = 0.0054). The 5-year local control rate and metastatic failure rate were 90% and 83.5%, respectively. Haematological effects were moderate. However, six pts had grade 3 acute intestinal toxicity. Four severe late complications requiring surgical intervention were observed (one small bowel complication, three ureteral complications).Conclusion. – Primary concomitant chemoradiation followed surgery for bulky operable stage I–II cervical carcinomas can be employed with acceptable toxicity. However, systematic preoperative uterovaginal brachytherapy should increase local tumour control.Cancer/Radiothérapie 06/2004; 8(3):168-177. · 1.11 Impact Factor