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Diagnostics
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Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer
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Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 13693

Special Issue Editors

Dr. Angela Santoro

E-Mail Website
Guest Editor
General Pathology Unit, Department of Woman and Child’s Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: breast pathology; gynecological oncology; molecular pathology
Special Issues, Collections and Topics in MDPI journals
Dr. Gian Franco Zannoni

E-Mail Website
Guest Editor
General Pathology Unit, Department of Woman and Child’s Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: breast pathology; gynecological oncology; molecular pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cervical cancer is the fourth most common cancer in women worldwide, and the second most common in low- and middle-income countries. Clinical stage is the most significant prognostic factor. Locally advanced cervical cancer (LACC) is defined as a ≥4 cm mass, being classified as FIGO stages IB2-IVA, with involvement of the lower third of the vagina and/or extension to the pelvic wall, and/or hydronephrosis or non-functioning kidney and/or involvement of pelvic and/or paraaortic lymph nodes. Neoadjuvant radiochemotherapy followed by surgery or perioperative treatment is well established as current standard treatment for LACC. The effects of preoperative treatment can be evaluated by histology, and determination of tumor regression is frequently integrated in the pathology reports of resection specimens. Histopathological determination of tumor regression provides important prognostic information. Regression grading systems mostly refer to the number of neoplastic cells, induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor compared to the former tumor site. Currently, there is no agreement and common standard for processing resection specimens after neoadjuvant treatment and for reporting of tumor regression for cervix cancers, but several different scores have been proposed. It is still a matter of debate which system may provide better results in terms of interobserver agreement or prognostic value. In order to improve cervix cancer care, we retain that future studies are necessary for the implementation of the best classification system, able to correctly define the tumoral bed. Finally, an adequate tumor regression scoring system with significant correlation with outcome could be considered an important piece of the puzzle in tailored therapies for patients with LACC.

Dr. Angela Santoro
Prof. Gian Franco Zannoni
Guest Editors

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Keywords

  • neoadjuvant therapy
  • cervical cancer
  • prognosis
  • molecular alterations

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Published Papers (5 papers)

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Research

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10 pages, 807 KiB  
Article
Pretreatment Radiologically Enlarged Lymph Nodes as a Significant Prognostic Factor in Clinical Stage IIB Cervical Cancer: Evidence from a Taiwanese Tertiary Care Center in Reaching Consensus
by Chia-Hao Liu, Szu-Ting Yang, Wei-Ting Chao, Jeff Chien-Fu Lin, Na-Rong Lee, Wen-Hsun Chang, Yi-Jen Chen and Peng-Hui Wang
Diagnostics 2022, 12(5), 1230; https://doi.org/10.3390/diagnostics12051230 - 14 May 2022
Cited by 10 | Viewed by 2021
Abstract
The incidence of lymph node (LN) involvement and its prognostic value based on radiological imaging in stage IIB cervical cancer (CC) remains unclear, and evidence regarding oncological outcomes of patients with stage IIB CC with LN metastases is limited. In this study we [...] Read more.
The incidence of lymph node (LN) involvement and its prognostic value based on radiological imaging in stage IIB cervical cancer (CC) remains unclear, and evidence regarding oncological outcomes of patients with stage IIB CC with LN metastases is limited. In this study we retrospectively reviewed the incidence and prognostic significance of pretreatment radiologic LN status in 72 patients with clinical stage IIB CC (FIGO 2009), with or without radiologic evidence of LN enlargement. An enlarged LN was defined as a diameter > 10 mm on CT/MRI. Progression-free survival (PFS) and overall survival (OS) were assessed. Radiologic LN enlargement of >10 mm was observed in 45.8% of patients with stage IIB CC. PFS (p = 0.0088) and OS rates (p = 0.0032) were significantly poorer in the LN group (n = 33) than in the non-LN group (n = 39). Univariate Cox analysis revealed that LN > 10 mm contributed to a higher rate of recurrence and mortality. In conclusion, nearly half of the patients with clinical stage IIB CC had enlarged LNs (>10 mm) identified during pretreatment radiologic evaluation, which negatively impacted prognosis. Our findings highlight the need to incorporate CT- or MRI-based LN assessment before treatment for stage IIB CC. Full article
(This article belongs to the Special Issue Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer)
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9 pages, 680 KiB  
Article
Margin Status Post Cervical Conization Predicts Residual Adenocarcinoma In Situ (AIS) and Occult Adenocarcinoma in a Predominantly Hispanic Population
by Linda J. Hong, Sandy Huynh, Joy Kim, Laura Denham, Mazdak Momeni and Yevgeniya J. M. Ioffe
Diagnostics 2021, 11(10), 1889; https://doi.org/10.3390/diagnostics11101889 - 13 Oct 2021
Cited by 1 | Viewed by 2743
Abstract
Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate [...] Read more.
Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate how conization margin status correlates with residual disease upon hysterectomy. Methods: A retrospective study utilizing a comprehensive cancer center database was conducted. Data from patients with histologically proven AIS of the cervix were abstracted. Results: Of 47 patients that met the criteria, 23 (49%) were Hispanic, 21 (45%) were White, two (4%) were Asian, and one (2%) was Black. The median age was 37. Forty-two patients underwent cervical conizations; 13/42 (48%) had positive margins upon conization; 28/42 (67%) underwent hysterectomies. Furthermore, 6/13 (46%) patients with positive conization margins had residual disease in hysterectomy specimens, with 2/13 (15%) found to have invasive cancer. In contrast, 0/14 (0%) of patients with negative margins had residual disease (p = 0.036, Chi-squared 4.41, df = 1). In total, 2/27 (7%) patients who underwent hysterectomies had invasive cancer (7%). Conclusions: Positive margins upon cervical conization for AIS of the cervix were correlated with a relatively high rate of residual AIS and occult invasive cancer. Negative conization margins were correlated with no residual disease. Those patients may be candidates for fertility-sparing treatment. Full article
(This article belongs to the Special Issue Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer)
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13 pages, 1088 KiB  
Article
Prediction Model for Tumor Budding Status Using the Radiomic Features of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Cervical Cancer
by Gun Oh Chong, Shin-Hyung Park, Shin Young Jeong, Su Jeong Kim, Nora Jee-Young Park, Yoon Hee Lee, Sang-Woo Lee, Dae Gy Hong, Ji Young Park and Hyung Soo Han
Diagnostics 2021, 11(8), 1517; https://doi.org/10.3390/diagnostics11081517 - 23 Aug 2021
Cited by 8 | Viewed by 2502
Abstract
Objective: To compare the radiomic features of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and intratumoral heterogeneity according to tumor budding (TB) status and to develop a prediction model for the TB status using the radiomic feature of 18F-FDG [...] Read more.
Objective: To compare the radiomic features of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and intratumoral heterogeneity according to tumor budding (TB) status and to develop a prediction model for the TB status using the radiomic feature of 18F-FDG PET/CT in patients with cervical cancer. Materials and Methods: Seventy-six patients with cervical cancer who underwent radical hysterectomy and preoperative 18F-FDG PET/CT were included. We assessed the status of intratumoral budding (ITP) and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Three conventional metabolic parameters and fifty-nine features were extracted and analyzed. Univariate analysis was used to identify significant metabolic parameters and radiomic findings for TB status. The prediction model for TB status was built using 3 machine learning classifiers (random forest, support vector machine, and neural network). Results: Univariate analysis led to the identification of 2 significant metabolic parameters and 12 significant radiomic features according to intratumoral budding (ITB) status. Among these parameters, following multivariate analysis for the ITB status, only compacity remained significant (odds ratio, 5.0047; 95% confidence interval, 1.1636–21.5253; p = 0.0305). Two conventional metabolic parameters and 25 radiomic features were selected by the Lasso regularization, and the prediction model for the ITB status had a mean area under the curve of 0.762 in the test dataset. Conclusion: Radiomic features of 18F-FDG PET/CT were associated with the ITB status. The prediction model using radiomic features successfully predicted the TB status in patients with cervical cancer. The prediction models for the ITB status may contribute to personalized medicine in the management of patients with cervical cancer. Full article
(This article belongs to the Special Issue Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer)
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9 pages, 600 KiB  
Article
Prognostic Factors Associated with 5-Year Overall Survival in Cervical Cancer Patients Treated with Radical Hysterectomy Followed by Adjuvant Concurrent Chemoradiation Therapy at a Tertiary Care Center in Eastern Europe
by Mihai Stanca and Mihai Emil Căpîlna
Diagnostics 2021, 11(3), 570; https://doi.org/10.3390/diagnostics11030570 - 22 Mar 2021
Cited by 13 | Viewed by 2633
Abstract
Background: This retrospective observational study aims to assess the 5-year overall survival and the prognostic significance of risk factors of patients who underwent radical hysterectomy followed by adjuvant concurrent chemoradiation therapy (CCRT) for FIGO stage IB1-IIB cervical cancer in a tertiary care center [...] Read more.
Background: This retrospective observational study aims to assess the 5-year overall survival and the prognostic significance of risk factors of patients who underwent radical hysterectomy followed by adjuvant concurrent chemoradiation therapy (CCRT) for FIGO stage IB1-IIB cervical cancer in a tertiary care center in Eastern Europe. Methods: From January 2010 to February 2019, 222 patients with stage IB1-IIB cervical cancer were treated with radical hysterectomy followed by adjuvant CCRT in our institution. The baseline information consisting of demographic and clinicopathologic data, treatment choices, recurrences, and outcome information was collected and examined. The survival rates were illustrated using Kaplan–Meier curves and prognosis analyses were accomplished using Cox multivariate analyses. Results: The 222 participants had a mean age of 51.2 years (28–76). The median follow-up time was 65.5 months (3–128). Tumor characteristics revealed FIGO stage (IB1 2.3%, IB2 35.1%, IB3 16.7%, IIA1 9%, IIA2 8.6%, IIB 28.4%) and the most encountered histologic cell type was squamous cell carcinoma (80.06%) followed by adenocarcinoma (11.3%). At the time of examination, 157 patients (70.07%) were alive, of which 135 (61%) were alive free of disease and 22 (9%) were alive with disease. The multivariate Cox regression analysis acknowledged stage IIB, parametrial involvement, and the presence of lymph node metastases as independent prognostic risk factors, significantly worsening the oncologic outcomes influencing the survival with a P-value of 0.076, 0.0001, and 0.008, respectively. The 5-year overall survival was 69.9%. Conclusions: Altogether, the study enhances the significance of prognostic risk factors on the 5-year overall survival of patients who underwent radical hysterectomy followed by adjuvant CCRT for FIGO stages IB1-IIB cervical cancer, allowing comparisons with other regions. Full article
(This article belongs to the Special Issue Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer)
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Review

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11 pages, 1733 KiB  
Review
Depth of Stromal Invasion as the Most Prognostically Relevant Regression System in Locally Advanced Cervical Cancer after Neoadjuvant Treatment: A Systematic Review and Meta-Analysis Grading
by Gian Franco Zannoni, Antonio Travaglino, Antonio Raffone, Damiano Arciuolo, Nicoletta D’Alessandris, Giulia Scaglione, Pietro Tralongo, Frediano Inzani, Giuseppe Angelico and Angela Santoro
Diagnostics 2021, 11(10), 1772; https://doi.org/10.3390/diagnostics11101772 - 26 Sep 2021
Cited by 12 | Viewed by 2735
Abstract
Background: several different criteria have been proposed to categorize the pathological response in cervical cancer after neoadjuvant therapy; although it is unclear what the most prognostically valuable one is. Objective: to assess the prognostic value of pathological criteria for categorizing the response in [...] Read more.
Background: several different criteria have been proposed to categorize the pathological response in cervical cancer after neoadjuvant therapy; although it is unclear what the most prognostically valuable one is. Objective: to assess the prognostic value of pathological criteria for categorizing the response in cervical cancer after neoadjuvant therapy, through a systematic review and meta-analysis. Methods: four electronic databases were searched from January to December 2020 for all studies, assessing the prognostic value of pathological response in cervical cancer after neoadjuvant therapy. Hazard ratio (HR) for overall survival (OS) was calculated with a significant p-value < 0.05. A meta-analysis was performed for each criteria assessed in at least three studies. Results: sixteen studies were included. Criteria for pathological response included (i) residual stromal invasion < vs. >3 mm; (ii) complete response vs. any residual; (iii) proportion of viable cells; (iv) residual tumor diameter; and (v) intracervical vs. extracervical residual. Criteria (i) and (ii) were suitable for meta-analysis. The presence of a residual tumor with stromal invasion > 3 mm showed a HR of 4.604 (95% CI; 3.229–6.565; p < 0.001), while the presence of any residual showed a HR of 1.610 (95% CI; 1.245–2.081; p < 0.001); statistical heterogeneity was absent in both analyses. Conclusions: dichotomizing the pathological response in cervical cancer after neoadjuvant therapy as < vs. >3 mm stromal invasion is more prognostically valuable than dichotomizing as complete response vs. any residual. Further studies are necessary to evaluate other systems. Full article
(This article belongs to the Special Issue Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer)
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