ESGO-ESTRO-ESP Guidelines cervical cancer

NICOLÒ BIZZARRI

ENYGO chair

Gynecologic Oncology Unit

Policlinico Agostino Gemelli IRCCS

Rome, ITALY

GENERAL RECOMMENDATIONS

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

FIGO IA1 CERVICAL CANCER

FIGO IA1-IA2 CERVICAL CANCER

1567 patients with adenocarcinoma

5749 SCC

FIGO stage IA1 and IA2

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There was no statistical difference in survival between patients having either histology undergoing

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• local excision
• simple hysterectomy
• radical hysterectomy

Am J Obstet Gynecol. 2017;217(3):332.e1-332.e6.

FIGO IB1-IIA1 CERVICAL CANCER

Int J Gynecol Cancer. 2020;30(1):15.

In light of the results obtained by these studies the European Society of Gynaecological Oncology (ESGO) Scientific Committee and Council herewith issues a statement that the current ESGO recommendation regarding the approach for radical surgery for cervical cancer (“minimal invasive approach is favored”) is no longer valid.

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It should be removed and replaced by

“OPEN APPROACH IS THE GOLD STANDARD”.

MIS in cervical cancer should be:

• prospectively recorded
• only in highly specialised centres
• appropriately trained surgeons
• avoid spillage of tumour cells in the peritoneal cavity
• patients must be informed about the available prospective and retrospective evidence on survival

FIGO IB1-IIA1 CERVICAL CANCER

Rychlik A, Angeles MA, Migliorelli F, et al. Int J Gynecol Cancer. 2020;30(3):358-363. 

Macrometastatic disease was missed on frozen section in 3/13 (23.1%) FIGO 2018 stage IIIC patients. The three patients with ITC were also missed by frozen section examination.

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Including micrometastases, sensitivity was 81.2% and NPV was 97.9%.

Cibula D, Kocian R, Plaikner A, et al. Eur J Cancer. 2020;137:69-80.

FIGO IB1-IIA1 CERVICAL CANCER

ABRAX TRIAL: Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement

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• COMPLETION group, n=361
• ABANDON group, n=154
• 91.4% of COMPL group underwent adjuvant chemoradiation, 100% of ABAND group were treated with primary chemoradiation
• Median follow-up of 48.9 months
• No significant difference was found between the groups in the risk of recurrence (HR=1.154; p=0.446), local recurrence (HR=0.836; p=0.557), or death (HR=1.064; p=0.779)
• Higher EARLY treatment-related complications in COMPLETION (p=0.040) vs higher LATE treatment-related complications in ABANDON group (p=0.030)

Cibula D, Dostalek L, Hillemanns P, et al. Eur J Cancer. 2021;143:88-100

FIGO IB1-IIA1 CERVICAL CANCER

Retrospective, multi-center, observational cohort study

419 patients <50 years with clinical FIGO 2009 stage IA1-IB1/IIA1 cervical carcinoma

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• Ovarian transposition performed in 28/155 (18.1%) patients
• 1/264 (0.4%) patient had ovarian metastasis from endocervical adenocarcinoma

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• 5-year DFS of patients undergoing CONSERV versus OOPHOR was 90.6% versus 82.2%, respectively (p=0.028); no OS difference
• Two patients (1.3%) developed recurrence on the conserved ovary
• CONSERV represented an independent protective factor of recurrence (HR:0.361, 95%CI 0.169-0.769; p=0.008)

FIGO IB1-IIA1 CERVICAL CANCER

There are no significant differences in terms of both recurrence rate and overall survival among patients with stage IB-IIA cervical cancer undergoing simple extrafascial hysterectomy (class I) or radical hysterectomy (class III). Morbidity is proportional to the extent of radicality.

Class II and class III radical hysterectomies are equally effective in surgical treatment of cervical carcinoma, but the former is associated with a lesser degree of late complications.

FIGO IB1-IIA1 CERVICAL CANCER

• The extent of parametrectomy had no influence on survival in tumors of 20 mm or less.
• DFS was significantly better in tumors 20-40 mm and >40 mm if more radical hysterectomy was performed.

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For larger tumors, a more radical hysterectomy might be associated with better DFS.

FIGO IB1-IIA1 CERVICAL CANCER

Front Oncol. 2018;8:568

• Midterm analysis
• No 2-y DFS difference
• Type II hysterectomy can effectively reduce the surgical time and intraoperative blood loss, decrease postoperative complications, and improve the quality of life of early-stage cervical cancer patients.

FIGO IB1-IIA1 CERVICAL CANCER

INTERMEDIATE RISK FACTORS

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Combination of:

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• Depth of stromal infiltration
• Tumor diameter
• LVSI

HIGH RISK FACTORS

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At least one:

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• N+
• Parametrium +
• Surgical margins +

ADJUVANT RT

ADJUVANT CT-RT

FIGO IB1-IIA1 CERVICAL CANCER

• Retrospective cohort study
• Stage IB; LN negative
• Prognostic factors:
• LVSI + deep stromal invasion OR
• LVSI and tumour size ≥ 2 cm OR
• Tumour size ≥ 4 cm
• Primary surgical treatment 1/2005 - 12/2015
• Three institutions
• Prague (NO adjuvant treatment in IR group)
• MSKCC + Melbourne (Adjuvant chemoradiotherapy in IR group)

Cibula D, Abu-Rustum NR, Fischerova D, et al.

Gynecol Oncol. 2018;151(3):438-443.

FIGO IB1-IIA1 CERVICAL CANCER

• Phase III, international, multicenter, randomized, non-inferiority trial
• 514 eligible patients (including 10% expected drop-out) will be randomized
• Intermediate-risk early-stage cervical cancer
• Primary Endpoint: DFS
• It is estimated that the accrual will be completed by 2027 and primary endpoint results will be published by 2031
• Estimated trial completion with OS is by 2034

Int J Gynecol Cancer. 2022;ijgc-2022-003918.

Trial Registration NCT04989647

FIGO IB1-IIA1 CERVICAL CANCER

• 13 patient
• Clinical response rate was 84.5% (11 out of 13 patients)
• Median follow-up was 37 months (range 18–76)
• One distant recurrence, 12 months after CKC, in the liver
• Pegnancy rate of 66.7%

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

FIGO IB3-IVA CERVICAL CANCER

NCI Clinical Announcement on concurrent

chemoradiation for cervical cancer – 1999

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"strong consideration should be given to the

incorporation of concurrent cisplatin based

chemotherapy in women who require radiation

therapy for treatment of cervical cancer"

NCI Issues Clinical Announcement on Cervical Cancer: Chemotherapy Plus Radiation Improves Survival.

FIGO IB3-IVA Pelvic N+ CERVICAL CANCER

ACCURACY OF DIFFERENT METHODS OF DIAGNOSING PA N+

Smits et al. IJGC 2014

Marnitz et al. IJGC 2020

Gouy et al. Lancet Oncol 2012

Gouy at al. JCO 2013

Cartron et al. Gynecol Obstet Fertil 2005

Gouy et al. JCO 2013

Kohler et al. AJOG 2015

ROLE OF STAGING PARA-AORTIC LND: RCTs

Closed for LACK OF ACCRUAL

ROLE OF STAGING PARA-AORTIC LND: RCTs

Lai et al. Gynecol Oncol 2003

Conclusion: 

The benefit of pretreatment surgical staging for cervical carcinoma remained unproven. The detrimental effects of surgical staging observed in this study must be considered in the design of clinical guidelines or future trials.

ROLE OF STAGING PARA-AORTIC LND: RCTs

Marnitz S, Tsunoda AT, Martus P, et al. Int J Gynecol Cancer. 2020;30(12):1855-1861.

ROLE OF STAGING PARA-AORTIC LND: RCTs

UTERUS-11 TRIAL

Major limitations:

• no PET/CT scan
• ITT population lowered power of study (beta 70%)

Conclusion:

• No difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer.
• There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging.

P<0.05

Marnitz S, Tsunoda AT, Martus P, et al. Int J Gynecol Cancer. 2020;30(12):1855-1861.

ROLE OF STAGING PARA-AORTIC LND: RCTs

Int J Gynecol Cancer. 2022;ijgc-2022-003953

Int J Gynecol Cancer. 2022;ijgc-2022-003910

PAROLA TRIAL

The PAROLA trial is an international multicentric study that aims to evaluate 3-year disease-free survival benefit of para-aortic surgical staging in patients with stage IIIC1r cervical cancer on pretreatment PET/CT.

FIGO IB3-IVA Bulky N+ CERVICAL CANCER

• 381 women with LACC
• Retrospective multicenter study
• Group 1 LN debulking and para-aortic LND
• Group 2 para-aortic LND
• Group 3 no lymph node surgical staging

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• No DFS or OS difference
• No difference in intra or post-op complications

FIGO IB3-IVA Bulky N+ CERVICAL CANCER

• FIGO 2009 stage IB2, IIA2–IVA cervical cancer with lymph nodes ≥1.5 cm
• Retrospective multicenter study
• 101 (53%) nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) neither treatment

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• No difference in RFS and OS

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• Combination of debulking with boosting was associated with decreased RFS and OS compared with debulking alone (worse prognosis??)
• Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy

Int J Gynecol Cancer. 2022;32(7):861-868.

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

FIGO IVB/RECURRENT CERVICAL CANCER

Int J Gynecol Cancer. 2022;32(6):732-739.

• 83 patients with oligometastatic/persistent/recurrent cervical cancer with 125 lesions treated by stereotactic body radiotherapy
• Forty-six (55.4%) patients had a complete response
• Fifteen patients (18.1%) had mild acute toxicity
• Late toxicity was documented in four patients (4.8%)

RECURRENT CERVICAL CANCER AFTER RT

RECURRENT CERVICAL CANCER AFTER RT

Retrospective analysis

63 patients

LEPR was defined as an en bloc lateral resection of a pelvic tumour involving sidewall muscle, and/or bone, and/or major nerve, and/or major vascular structure

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Negative surgical margins achieved in 85.7% patients

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Major postoperative complications occurred 27.7% patients

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Negative surgical margins major prognostic factor

Although the LEPR is associated

with considerable morbidity (≈ 30%), a long-term survival seems to be achieved in those women with completeresection.

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

ESGO-ESTRO-ESP GUIDELINES CERVICAL CANCER

FOLLOW UP AFTER TREATMENT

FOLLOW UP AFTER TREATMENT

The annual risk of recurrence model from SCCAN study represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient’s risk status and respective annual recurrence risk.

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It can easily be used in routine clinical settings internationally.

Cibula D, Dostálek L, Jarkovsky J, et al. The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer. Eur J Cancer. 2021;158:111-122

Also included in the ESGO-ESTRO-ESP guidelines

2022 ESGO-ESTRO-ESP guidelines cervical cancer