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Internal Validation of a Predictive Model for Overall Survival in Patients with FIGO stages I–IV Cervical Cancer

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Abstract

Purpose

To identify prognostic factors and to achieve the internal validation of a predictive model for overall survival in patients with cervical cancer at any stage.

Methods

A prospective cohort study was conducted between January 2010 and January 2019 on 229 women with cervical cancer. We performed a survival analysis using the Kaplan–Meier method and log-rank test, and, finally, developed a Cox model.

Results

Overall survival was 41 (IQR = 57.5) months (R = 1–264), with a cancer-specific mortality rate of 26.2%. We found significant differences in the median overall survival between the early and the locally advanced stages (43 versus 11 months, P = 0.001) and between the early and the advanced stages (40 versus 11 months, P = 0.003). There were no significant differences in the 5-year overall survival between the monotherapy based on types B and C2 radical hysterectomy (P = 0.1) and between the radical and the extrafascial hysterectomy (P = 0.2). Regarding the surgical approach for type B radical and total extrafascial hysterectomy, we could not study differences between laparotomic and laparoscopic routes due to a lack of enough amount of power. We developed a model with a Harrell´s concordance index of 0.87. The predictors of the model were primary surgery, maximum tumor diameter, and type of therapeutic response.

Conclusion

The cancer-specific mortality rate was 26.2%. We developed a model that, once statistical power was increased and externally validated, might provide useful prognostic information for both patients and oncologists at first consultation.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to the fact that their containing information could compromise the privacy of research participants.

Code Availability

Not applicable.

Abbreviations

ACC:

Advanced cervical cancer

BMI:

Body mass index

CC:

Cervical cancer

CI:

Confidence interval

C-index:

Harrell´s concordance index

C-section:

Cesarean section

DF:

Degrees of freedom

DSI:

Deep stromal invasion

ECC:

Early cervical cancer

ECOG:

Eastern Cooperative Oncology Group

EE:

Error estimate

Exp(βn):

Relative risk

FIGO:

International Federation of Gynecology and Obstetrics

GR:

Grade of recommendation

HPV:

Human papillomavirus

HR:

High-risk

IQR:

Interquartile range

LACC:

Laparoscopic approach to cervical cancer

LCC:

Locally advanced cervical cancer

LE:

Level of evidence

LHR:

Likelihood ratio

LVI:

Lymphovascular invasion

Me :

Median

MLN:

Metastatic lymph node

MPALN:

Metastatic para-aortic lymph node

MPLN:

Metastatic pelvic lymph node

MTD:

Maximum tumor diameter

N:

Sample size

NA:

Not available

NCI:

National Cancer Institute

OS:

Overall survival

PAL:

Para-aortic lymphadenectomy

PI:

Parametrial invasion

PL:

Pelvic lymphadenectomy

PS:

Performance status

R:

Range

RFS:

Recurrence-free survival

RH:

Radical hysterectomy

SD:

Standard deviation

SEER:

Surveillance, Epidemiology, and End Results

SIGN:

Scottish Intercollegiate Guidelines Network

SLNB:

Sentinel lymph node biopsy

:

Arithmetic mean

TEH:

Total extrafascial hysterectomy

VIF:

Variance inflation factor

Z-value:

Test de Wald

βn :

Predictor regression coefficient

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Inmaculada Rodríguez Jiménez

    Present address: Clinical Management Unit for Obstetrics and Gynecology, University Hospital Virgen Macarena, 3 Dr. Fedriani Ave, 41009, Seville, Spain

Authors and Affiliations

  1. Clinical Management Unit for Obstetrics and Gynecology, University Hospital Virgen Macarena, 3 Dr. Fedriani Ave, 41009, Seville, Spain

    Jorge Cea García & Francisco Márquez Maraver

  2. Institute of Science and Technology, Loyola University, De las Universidades Ave, 41704, Dos Hermanas, Seville, Spain

    Laura Ríos-Pena

  3. Department of Radiation Oncology, University Hospital Sanchinarro, 10 De Oña St., 28050, Madrid, Spain

    M. Carmen Rubio Rodríguez

  4. Department of Radiation Oncology, Hospital Puerta del Sur, 70 Carlos V Ave, 28 938, Móstoles, Madrid, Spain

    M. Carmen Rubio Rodríguez

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Contributions

All authors met the authorship criteria. JCG: Investigation, Conceptualization, Methodology, Writing-Original draft preparation, Visualization, Writing-Reviewing and Editing. LRP: Methodology, Software, Data Curation, Formal analysis, Validation, Writing-Reviewing and Editing, and Supervision. MCRR: Supervision. FMM: Resources and Supervision. IRJ: Resources and Supervision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jorge Cea García.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest or financial support.

Informed Consent

The research assistant obtained a written informed consent from each subject before each interview to participate and publish her data; participants were assured that they could stop the study process at any time and were assured that nonparticipation would have no consequences for their follow-up care or therapy. There was no refund for the participants.

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Appendices

Appendix I

Statistical analysis of the confounding factors of the association between the overall survival and the type of surgery/surgical approach. P-values are presented in the Table.

BRH vs. C2 RH

Laparoscopy

Laparotomy

2/TEH 19

Laparoscopy

Laparotomy

Surgical approach

34

13

34

13

N

BRH 4+5

BRH  +  2CRH 15

BRH  + C2RH 8/TEH 5

Type of surgery

1

0.358

 

0.184

Age

1

0.676

 

0.187

Comorbidities

1

0.473

 

–

Baseline PS

1

0.357

 

0.699

FIGO stage

0.22

0.199

 

0.596

Histological type

0.877

0.421

 

0.285

Histological grade

1

0.42

 

0.418

LVI

0.928

0.942

 

0.1

DSI

0.207

0.326

 

0.156

MTD

–

0.695

 

0.695

MTD ≥ 20 mm

–

–

 

0.521

Surgical technique

1

0.446

 

0.027

PL

0.17

0.451

 

0.381

PLNs

removed

–

–

 

0.119

PALNs

removed

1

1

 

1

MLNs

1

0.25

 

1

Recurrence

-

0.156

 

0.002

Follow-up duration

DSI deep stromal invasion, TEH total extrafascial hysterectomy, FIGO International Federation of Gynecology and Obstetrics, LVI lymphovascular invasion, MLN metastatic lymph node, MTD maximum tumor diameter, N sample size, PL pelvic lymphadenectomy, PLN pelvic lymph node, PALN para-aortic lymph node, PS performance status, RH radical hysterectomy.

Appendix II

Statistical analysis of the background variables and confounding factors of the association between the overall survival and the surgical approach in patients submitted to type B radical hysterectomy and in patients who underwent radical surgery alone vs. total extrafascial hysterectomy

Variables

Type B RH laparotomy (N = 4) vs. laparoscopy (N = 5) (p)

Radical surgery alone (N = 16) vs. TEH (N = 30) (p)

Age at diagnosis of CC

0.358

0.753

Menopausal state at diagnosis

0.919

0.794

Smoking prior to CC

0.072

0.794

BMI

0.07

0.228

Origin

0.268

0.289

Nationality

0.089

0.29

Marital status at survey

0.789

0.48

Religion

0.333

0.697

Social stratum

0.829

0.539

Educational level

0.176

0.67

Occupation

0.402

0.671

Comorbidities

0.676

0.877

Depression prior to CC

0.61

0.457

Prior C-section

0.409

0.39

Histological type

0.199

0.342

Histological grade

0.421

0.005

Low 43.75% < 76.67%

High

43.75% > 6.67%

LVI

0.42

0.457

MTD

0.326

0.002

21.6 vs. 5.88 mm

Stromal invasion

0.942

0.001

 < 1/3 31.25% < 73.33%

CC stage

0.357

 < 0.0001

IA1 18.75% < 83.33%

IB1

10% < 93.75%

Baseline PS score

0.473

1

Ovarian preservation

0.632

0.457

SLNB

0.012

Laparoscopy > laparotomy

 < 0.0001

43.75% > 0%

PL

0.446

 < 0.0001

100% > 13.33%

PAL

0.007

Laparotomy > laparoscopy

0.026

18.75 > 0%

Number of PLNs removed

0.451

0.85

Number of MPLNs removed

1

1

Intraoperative complications

0.729

0.731

Postoperative complications

0.025

27.27 vs. 64.52%

0.413

Overall complications 0.342

Time interval to diagnosis of surgical

complication

0.036

21 vs. 5.5 days

0.502

Length of hospital stay

0.007

6.11 vs. 3.22 days

0.018

5.07 vs. 2.68

Number of recurrences

0.25

1

Follow-up time > 2 years

 < 0.0001

100% vs. 71.88%

0.363

BMI body mass index, CC cervical cancer, C-section cesarean section, LVI lymphovascular invasion, MPLN metastatic pelvic lymph node, MTD maximum tumor diameter, PL pelvic lymphadenectomy, PAL para-aortic lymphadenectomy, PLN pelvic lymph node, PS performance status, RH radical hysterectomy, SLNB sentinel lymph node biopsy, TEH total extrafascial hysterectomy.

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Cea García, J., Márquez Maraver, F., Rodríguez Jiménez, I. et al. Internal Validation of a Predictive Model for Overall Survival in Patients with FIGO stages I–IV Cervical Cancer. Indian J Gynecol Oncolog 21, 67 (2023). https://doi.org/10.1007/s40944-023-00744-2

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