Prognostic value of pretreatment FDG PET/CT in uterine cervical cancer according to two major histologic types: squamous cell carcinoma and adenocarcinoma

Document Type : Original Article


1 Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Japan

2 Department of Diagnostic Radiology, Japanese Red Cross Society Wakayama Medical Center, Japan

3 Department of Diagnostic Radiology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Japan


Objective(s): The aim of this study was to assess the prognostic value of pretreatment Positron emission tomography / computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT) in cervical cancer according to two major histologic types.
Methods: Eighty-three squamous cell carcinoma (SCC) patients and 35 adenocarcinoma (AC) patients who underwent pretreatment FDG-PET/CT were retrospectively analyzed. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were calculated. Kaplan-Meier analyses were used to compare correlations between each PET parameter and overall survival (OS). The prognostic values of imaging and clinical parameters were assessed using uni- and multivariable Cox proportional hazard models.
Results: SUVmax, SUVmean, and TLG were significantly higher in SCC than in AC (p<0.01 each). No significant difference in MTV was seen between the two groups (p=0.10). As for Kaplan-Meier analyses, in SCC, patients with SUVmax, SUVmean, MTV, and TLG exceeding cutoff values tended to show worse OS than patients with lower values (p=0.07, p=0.27, p<0.01, and p=0.01, respectively, for OS). On the other hand, in AC, patients with MTV and TLG exceeding cutoff values showed significantly worse PFS and OS (p<0.01 each for OS), while SUVmax and SUVmean were unrelated to OS (p=0.91 and p=0.83, respectively for OS). As for multivariable analyses, in SCC, TLG was identified as an independent prognostic factor for OS (p=0.01). In AC, MTV was identified as an independent prognostic factor for OS (p=0.02).
Conclusion: Our preliminary data suggest that FDG-PET/CT would be useful for predicting prognosis in cervical cancer, although the clinical significance of quantitative values may differ according to histopathological type.


Main Subjects

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136:E359-86.
  2. Gadducci A, Guerrieri ME, Cosio S. Adenocarcinoma of the uterine cervix: Pathologic features, treatment options, clinical outcome and prognostic variables. Crit Rev Oncol Hematol. 2019; 135:103-14.
  3. Williams NL, Werner TL, Jarboe EA, Gaffney DK. Adenocarcinoma of the cervix: should we treat it differently? Curr Oncol Rep. 2015; 17:17.
  4. Bray F, Carstensen B, Moller H, Zappa M, Zakelj MP, Lawrence G, et al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev. 2005; 14:2191-9.
  5. Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study. Gynecol Oncol. 2000; 78:97-105.
  6. Rose PG, Java JJ, Whitney CW, Stehman FB, Lanciano R, Thomas GM. Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in gynecologic oncology group trials of cisplatin-based chemoradiation. Gynecol Oncol. 2014; 135:208-12.
  7. Galic V, Herzog TJ, Lewin SN, Neugut AI, Burke WM, Lu YS, et al. Prognostic significance of adenocarcinoma histology in women with cervical cancer. Gynecol Oncol. 2012; 125:287-91.
  8. Park JY, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. Outcomes after radical hysterectomy in patients with early-stage adenocarcinoma of uterine cervix. Br J Cancer. 2010; 102:1692-8.
  9. Winer I, Alvarado-Cabrero I, Hassan O, Ahmed QF, Alosh B, Bandyopadhyay S, et al. The prognostic significance of histologic type in early stage cervical cancer - A multi-institutional study. Gynecol Oncol. 2015; 137:474-8.
  10. Spoozak L, Lewin SN, Burke WM, Deutsch I, Sun X, Herzog TJ, et al. Microinvasive adenocarcinoma of the cervix. Am J Obstet Gynecol. 2012; 206:80.e1-6.
  11. Scher N, Castelli J, Depeursinge A, Bourhis J, Prior JO, Herrera FG, et al. ((18)F)-FDG PET/CT parameters to predict survival and recurrence in patients with locally advanced cervical cancer treated with chemoradiotherapy. Cancer Radiother. 2018; 22:229-35.
  12. Cima S, Perrone AM, Castellucci P, Macchia G, Buwenge M, Cammelli S, et al. Prognostic Impact of Pretreatment Fluorodeoxy-glucose Positron Emission Tomography/ Computed Tomography SUVmax in Patients With Locally Advanced Cervical Cancer. Int J Gynecol Cancer. 2018; 28:575-80.
  13. Krhili S, Muratet JP, Roche S, Pointreau Y, Yossi S, Septans AL, et al. Use of Metabolic Parameters as Prognostic Factors During Concomitant Chemoradiotherapy for Locally Advanced Cervical Cancer. Am J Clin Oncol. 2017; 40:250-5.
  14. Hong JH, Min KJ, Lee JK, So KA, Jung US, Kim S, et al. Prognostic Value of the Sum of Metabolic Tumor Volume of Primary Tumor and Lymph Nodes Using 18F-FDG PET/CT in Patients With Cervical Cancer. Medicine (Baltimore). 2016; 95:e2992.
  15. Voglimacci M, Gabiache E, Lusque A, Ferron G, Ducassou A, Querleu D, et al. Chemoradiotherapy for locally advanced cervix cancer without aortic lymph node involvement: can we consider metabolic parameters of pretherapeutic FDG-PET/CT for treatment tailoring? Eur J Nucl Med Mol Imaging. 2019; 46:1551-9.
  16. Kidd EA, Siegel BA, Dehdashti F, Grigsby PW. The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer. 2007; 110:1738-44.
  17. Ueno Y, Lisbona R, Tamada T, Alaref A, Sugimura K, Reinhold C. Comparison of FDG PET metabolic tumour volume versus ADC histogram: prognostic value of tumour treatment response and survival in patients with locally advanced uterine cervical cancer. Br J Radiol. 2017; 90:20170035.
  18. Rahman T, Tsujikawa T, Yamamoto M, Chino Y, Shinagawa A, Kurokawa T, et al. Different Prognostic Implications of 18F-FDG PET Between Histological Subtypes in Patients With Cervical Cancer. Medicine (Baltimore). 2016; 95:e3017.
  19. Chou HH, Chang HP, Lai CH, Ng KK, Hsueh S, Wu TI et al. 18F-FDG PET in stage IB/IIB cervical adenocarcinoma/adenosquamous carcinoma. Eur J Nucl Med Mol Imaging. 2010,37:728-35.
  20. Matsuo K, Machida H, Mandelbaum RS, Konishi I, Mikami M. Validation of the 2018 FIGO cervical cancer staging system. Gynecol Oncol. 2019; 152:87-93.
  21. Bhatla N, Berek JS, Cuello Fredes M, Denny LA, Grenman S, Karunaratne K, et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet. 2019; 145:129-35.
  22. Sebastian TB, Manjeshwar RM, Akhurst TJ, Miller JV. Objective PET lesion segmentation using a spherical mean shift algorithm. Med Image Comput Comput Assist Interv. 2006; 9:782-9.
  23. Watanabe M, Nakamoto Y, Ishimori T, Saga T, Kido A, Hamanishi J, et al. Prognostic utility of FDG PET/CT in advanced ovarian, fallopian and primary peritoneal high-grade serous cancer patients before and after neoadjuvant chemotherapy. Ann Nucl Med. 2020; 34:128-35.
  24. Karamurzin YS, Kiyokawa T, Parkash V, Jotwani AR, Patel P, Pike MC, et al. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis. Am J Surg Pathol. 2015; 39:1449-57.
  25. Nishio S, Mikami Y, Tokunaga H, Yaegashi N, Satoh T, Saito M, et al. Analysis of gastric-type mucinous carcinoma of the uterine cervix - An aggressive tumor with a poor prognosis: A multi-institutional study. Gynecol Oncol. 2019; 153:13-9.
  26. Mikami Y. Gastric-type mucinous carcinoma of the cervix and its precursors - historical overview. Histopathology. 2020; 76:102-11.
  27. Yoo J, Choi JY, Moon SH, Bae DS, Park SB, Choe YS, et al. Prognostic significance of volume-based metabolic parameters in uterine cervical cancer determined using 18F-fluorodeoxyglucose positron emission tomography. Int J Gynecol Cancer. 2012; 22:1226-33.
  28. Xue F, Lin LL, Dehdashti F, Miller TR, Siegel BA, Grigsby PW. F-18 fluorodeoxyglucose uptake in primary cervical cancer as an indicator of prognosis after radiation therapy. Gynecol Oncol. 2006; 101:147-51.
  29. Crivellaro C, Signorelli M, Guerra L, De Ponti E, Buda A, Dolci C, et al. 18F-FDG PET/CT can predict nodal metastases but not recurrence in early stage uterine cervical cancer. Gynecol Oncol. 2012; 127:131-5.
  30. Grigsby PW, Siegel BA, Dehdashti F. Lymph node staging by positron emission tomography in patients with carcinoma of the cervix. J Clin Oncol. 2001; 19:3745-9.
  31. Hwang L, Bailey A, Lea J, Albuquerque K. Para-aortic nodal metastases in cervical cancer: a blind spot in the International Federation of Gynecology and Obstetrics staging system: current diagnosis and Future Oncol. 2015; 11:309-22.
  32. Khebbeb S, Rathat G, Serrand C, Bourdon A, Ferrer C, Duraes M. Interest of para-aortic lymphadenectomy for locally advanced cervical cancer in the era of PET scanning. Eur J Obstet Gynecol Reprod Biol. 2022; 272:234-239.
  33. Kidd EA, Spencer CR, Huettner PC, Siegel BA, Dehdashti F, Rader JS, et al. Cervical cancer histology and tumor differentiation affect 18F-fluorodeoxyglucose uptake. Cancer. 2009; 115:3548-54.
  34. de Geus-Oei LF, van Krieken JH, Aliredjo RP, Krabbe PF, Frielink C, Verhagen AF, et al. Biological correlates of FDG uptake in non-small cell lung cancer. Lung Cancer. 2007; 55:79-87.
  35. Lin AJ, Wright JD, Dehdashti F, Siegel BA, Markovina S, Schwarz J, et al. Impact of tumor histology on detection of pelvic and para-aortic nodal metastasis with (18)F-fluorodeoxyglucose-positron emission tomography in stage IB cervical cancer. Int J Gynecol Cancer. 2019; 29:1351-4.
  36. Kido A, Mikami Y, Koyama T, Kataoka M, Shitano F, Konishi I, et al. Magnetic resonance appearance of gastric-type adenocarcinoma of the uterine cervix in comparison with that of usual-type endocervical adenocarcinoma: a pitfall of newly described unusual subtype of endocervical adenocarcinoma. Int J Gynecol Cancer. 2014; 24:1474-9.
  37. Bonin L, Devouassoux-Shisheboran M, Golfier F. Clinicopathological characteristics of patients with mucinous adenocarcinoma of the uterine cervix: A retrospective study of 21 cases. J Gynecol Obstet Hum Reprod. 2019; 48:319-27.