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. 2021 Sep;162(3):532-538.
doi: 10.1016/j.ygyno.2021.06.017. Epub 2021 Jul 1.

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis

Kimberly Levinson  1 , Anna L Beavis  2 , Christopher Purdy  3 , Anne F Rositch  4 , Akila Viswanathan  5 , Aaron H Wolfson  6 , Michael G Kelly  7 , Krishnansu S Tewari  8 , Leah McNally  9 , Saketh R Guntupalli  10 , Omar Ragab  11 , Yi-Chun Lee  12 , David S Miller  13 , Warner K Huh  14 , Kelly J Wilkinson  15 , Nicola M Spirtos  16 , Linda Van Le  17 , Yovanni Casablanca  18 , Laura L Holman  19 , Steven E Waggoner  20 , Amanda N Fader  21
Affiliations

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis

Kimberly Levinson et al. Gynecol Oncol. 2021 Sep.

Erratum in

Abstract

Purpose: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment.

Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk.

Results: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI.

Conclusions: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Keywords: Adenocarcinoma; Adjuvant radiation; Cervical cancer; Stage I.

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Conflict of interest statement

Declaration of Competing Interest Dr. Van Le reports royalties from Wolters Kluwer (as an editor of TeLinde's textbook). Dr. Huh reports money paid to him from consultancy with DYSIS. Dr. Miller reports money paid to him from consultancy with Tesaro, Eisai, Incyte, Karyopharm, and Genentech as well as money paid to his institution from Merck. He also reports money paid to his institution from grants or grants pending with nVision Medical, Advenchen, Forty Seven, Merck, Syros, and US BIOTEST. Dr. Ragab reports money paid to him from Consultancy with Regeneron. Dr. Viswanathan reports employment with money paid to her from Elsevier as the Ediotr in Chief for Seminars in Radiation Oncology. She also has an R01 NIH grant with money to her institution, and she received textbook royalties from Springer. Dr. Tewari has received money paid to him from consultancy with Clovis, Merck, Abbvie, Amgen, GSK, and Astra-Zenega, as well as payment for lectures from Clovis, Merck, Abbvie, Amgen, GSK, Astra-Zenega. Drs. Levinson, Fader, Beavis, Wolfson, Waggoner, Guntupalli, Lee, Kelly, McNally, Casablanca, Rositch, Spirtos, Wilkinson, Holman and Chris Purdy have no financial disclosures.

Figures

Figure 1:
Figure 1:. RFS - Positive LVSI, superficial DOI, impact of TS (SCC and AC modeled separately) (online only)
* The impact of tumor size for AC tumors is significant with a 36 mo RFS of 0.88 vs. 0.55 for TS <2cm vs. ≥4cm. Alternatively, tumor size (<2cm vs. ≥4cm) in patients with SCC does not significantly change 36 month RFS (0.97 vs. 0.91).
Figure 2:
Figure 2:. RFS - Positive LVSI, TS 2–4cm, impact of DOI (SCC and AC modeled separately) (online only)
* The impact of deep invasion for SCC tumors is significant with a 36 mo RFS of 0.96 vs. 0.73. Alternatively, deep invasion (compared to superficial invasion) in patients with AC does not significantly change 36 month RFS (0.65 vs. 0.58).
Figure 3.
Figure 3.. AC Nomogram for Recurrence
For each variable, the assigned points are provided in parentheses after the level of the variable. For example, positive LVSI assigns 5.4 points. Utilize the tumor size variable based on whether there is positive or negative lymphovascular invasion: VI =P for positive lymphovascular invasion, VI=N for negative lymphovascular invasion.
Figure 4.
Figure 4.. SCC Nomogram for Recurrence
For each variable, the assigned points are provided in parentheses after the level of the variable. For example, positive LVSI assigns 1.8 points. Utilize the tumor size variable based on whether there is positive or negative lymphovascular invasion: VI =P for positive lymphovascular invasion, VI=N for negative lymphovascular invasion.
See this image and copyright information in PMC

Comment in

References

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