key: cord-0773195-e6f03vrd
authors: Matsuo, Koji; Huang, Yongmei; Matsuzaki, Shinya; Deshpande, Rasika R.; Klar, Maximilian; Roman, Lynda D.; Wright, Jason D.
title: Association between hysterectomy wait-time and all-cause mortality for micro-invasive cervical cancer: treatment implications during the coronavirus pandemic
date: 2021-07-23
journal: Arch Gynecol Obstet
DOI: 10.1007/s00404-021-06151-2
sha: d10678f17c367e2879e2b0f737d83e8c3e39c1fe
doc_id: 773195
cord_uid: e6f03vrd

nan

In 2021, a global pandemic caused by a novel coronavirus (COVID-19) continues to be a major health threat. In the United States, nearly 33.5 million people have tested positive for COVID-19 and over 602,400 patients have died from complications related to COVID-19 as of early July 2021 [1] . The pandemic crisis is stressing the healthcare systems creating unprecedented challenges in providing timely oncologic care. Multiple studies have demonstrated that COVID-19 has resulted in delayed cancer care [2, 3] .

A recent high-quality meta-analysis concluded that cancer treatment delay is associated with increased mortality in various malignancies, but valid data on cervical cancer remain scant [4] . Given that the majority of women with early-stage cervical cancer are treated surgically with hysterectomy, we examined the association between hysterectomy wait-time and oncologic outcomes for women with microinvasive cervical cancer.

This retrospective observational study examined women with stage IA squamous, adenocarcinoma, and adenosquamous carcinomas of the uterine cervix diagnosed from 2004 to 2015 in the National Cancer Database. All women underwent primary hysterectomy. Cases with no wait-time were excluded due to the assumption of occult malignancy. Associations between surgical wait-time, defined as time interval from cancer diagnosis to hysterectomy, and oncologic outcomes including surgical-pathological factors (pathological parametrical invasion, nodal metastasis, and lympho-vascular space invasion) and all-cause mortality were examined [5] .

A generalized linear regression model was used to assess the association between wait-time and pathologic characteristics. Binary logistic regression and Cox proportional hazards regression models with restricted cubic spline transformation of surgery wait-time were used to assess the nonlinear associations between outcome measures, adjusting for other patient and tumor characteristics. The Columbia University Institutional Review Board deemed exempted this study due to the use of publicly available data.

A total of 2732 women were examined. The median age was 43 (IQR 36-52) years. Squamous histology (n = 1792, 65.5%) and stage IA1 disease (n = 1185, 43.4%) were the most frequent tumor characteristics. The median hysterectomy wait-time was 6 (IQR 4-9) weeks. Non-Hispanic Black and Hispanic patients, and uninsured and Medicaid insurance were independently associated with longer hysterectomy wait-time in multivariable analysis (all, P < 0.001; Table 1 ). Longer hysterectomy wait-time was not associated with increased risks of pathological parametrial involvement, regional lymph node metastasis, or lympho-vascular space invasion ( Fig. 1A-C) . The median follow-up was 4.5 (IQR 2.2-7.2) years, and 136 (5.0%) deaths occurred. Longer hysterectomy wait-time was not associated with allcause mortality risk (P = 0.431; Fig. 1D ).

The observed result with absence of association between hysterectomy wait-time and mortality risk is somehow reassuring. Notably, our results for micro-invasive cervical cancer differ from data for stage IB tumors in which longer wait times to hysterectomy are associated with increased mortality [5] . Our findings may be due, at least in part, to the favorable prognosis for micro-invasive cervical cancer. Important limitations in this study included missing information on underlying reason of hysterectomy delay, comorbidities, occult cancer diagnosis, and use of excisional biopsy prior to hysterectomy.

As there are few data to describe the survival effect of delay in hysterectomy in cervical cancer [4, 6] , our analysis of stage IA tumors provides valuable information in the management of women with early-stage cervical cancer and suggests that recommendations by recent expert panels to postpone hysterectomy for 6-8 weeks among patients with early-stage cervical cancer in centers or regions with a high burden of COVID-19 disease are reasonable for stage IA disease and do not adversely impact survival [7] .

No number; SD, standard deviation; CI confidence interval; and NOS not otherwise specified Mean wait-time (weeks) from cervical cancer diagnosis to hysterectomy is shown § Estimated parameters (beta) from generalized linear regression model. *P < 0.05, **P < 0.001. Due to the collinearity between age < 40, facility location and type unknown categories, betas were non-estimated for facility location and type unknown categories Funding Ensign Endowment for Gynecologic Cancer Research (K.M.). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The data on which this study is based are publicly available upon request at https:// www. facs. org/ quali ty-progr ams/ cancer/ ncdb. . For all-cause mortality, lympho-vascular space invasion, pathological parametrial tumor involvement, and lymph node metastasis were additionally included as covariates in the multivariable Cox proportional hazard regression model Transparency The manuscript's corresponding author (J.D.W.) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. National Cancer Database is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The program is the source of the de-identified data used; and the program has not verified and is not responsible for the statistical validity of the data analysis or the conclusions derived by the study team.

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Effect of delay in surgical therapy for early-stage cervical cancer: an implication in the coronavirus pandemic

Wait-time for hysterectomy and survival of women with early-stage cervical cancer: a clinical implication during the coronavirus pandemic

COVID-19 global pandemic: options for management of gynecologic cancers