Impact of radiographically bulky nodes on recurrence and overall survival in patients with locally advanced cervical cancer

Purpose of investigation: The authors sought to investigate the significance of radiographically bulky nodes (BN) on progression free survival (PFS) and overall survival (OS) in patients with locally advanced cervical cancer (CC) in an era of cisplatin chemoradiation. Methods and Materials: The authors performed a retrospective, IRB-approved review of women with Stage IB1 to IVA CC undergoing primary chemoradiation with cisplatin from February 2000 to February 2015. BN were defined as > 1.5 centimeters on pretreatment imaging. Results: Of the 127 patients identified, 29 (22.8%) had radiographically BN. Median PFS was 16.6 months for patients with BN compared to 57.4 months for those without (p = 0.001). Median OS for patients with BN was not statistically different from for those without. BN had no impact on site of recurrence (p = 0.99). Both stage (p = 0.01) and BN (p = 0.01) were independently prognostic for PFS; only stage (p = 0.002) was prognostic for OS. Conclusions: For locally advance CC, BN disease shortened PFS but did not affect OS.

Cervical cancer; Bulky lymphadenopathy; Chemoradiation

[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.

[2] Siegel R.L., Miller K.D., Jemal A.: “Cancer statistics, 2016”. CA Cancer J. Clin., 2016, 66, 7.

[3] Goff B., Muntz H., Paley P., Tamimi H., Koh W., Greer B.E.: “Impact of Surgical Staging in Women with Locally Advanced Cervical Cancer”. Gynecol. Oncol., 1999, 74, 436.

[4] Podczaski E.S., Palombo C., Manetta A., Larson J., DeGeest K., Mortel R., Andrews C.: “Assessment of Pretreatment Laparotomy in Patients with Cervical Carcinoma prior to Radiotherapy”. Gynecol. Oncol., 1989, 75, 71.

[5] Chung C., Nahhas W., Stryker J., Curry S., Abt A.: “Analysis of factors contributing to treatment failures in stages IB and IIA carcinoma of the cervix”. Am. J. Obstet. Gynecol., 1980, 138, 550.

[6] Carl U.M., Bahnsen J., Wiegel T.: “Radiation therapy of para-aortic lymph nodes in cancer of the uterine cervix”. Acta Oncol., 1993, 32, 63.

[7] Kosary C.L.: “FIGO Stage, Histology, Histologic Grade, Age and Race as Prognostic Factors in Determining Survival for Cancers of the Female Gynecological System : An Analysis of 1973-87 SEER Cases of Cancers of the Endometrium, Cervix, Ovary, Vulva, and Vagina”. Semin. Surg. Oncol., 1994, 46, 31.

[8] Cosin J.A., Fowler J.M., Chen M.D., Paley P.J., Carson L.F., Twiggs L.B.: “Pretreatment surgical staging of patients with cervical carcinoma: the case for lymph node debulking”. Cancer, 1998, 82, 2241.

[9] Hacker N., Wain G., Nicklin J.: “Resection of bulky positive lymph nodes in patients with cervical carcinoma”. Int. J. Gynecol. Cancer, 1995, 5, 250.

[10] Fletcher G.H.: “Subclinical Disease”. Cancer, 1984, 53, 1274.

[11] Perez C.A., Grigsby P.W., Nene S.M., Camel H.M., Galaktos A., Kao M.S., Lockett M.A.: “Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone”. Cancer, 1992, 69, 2796.

[12] Eifel P., Morris M., Wharton J., Oswald M.J.: “The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell carcinoma of the uterine cervix”. Int. J. Radiat. Oncol. Biol. Phys., 1994, 29, 9.

[13] Vargo J.A., Kim H., Choi S., Sukumvanich P., Olawaiye A.B., Kelley J.L.: “Extended field intensity modulated radiation therapy with concomitant boost for lymph node-positive cervical cancer: Analysis of regional control and recurrence patterns in the positron emission tomography/computed tomography era”. Int. J. Radiat. Oncol. Biol. Phys., 2014, 90, 1091.

[14] Wharton J.T., Jones III H.W., Day Jr. T.G., Rutledge F.N., Fletcher G.H.: “Preirradiation celiotomy and extended field irradiation for invasive carcinoma of the cervix”. Obstet. Gynecol., 1977, 49, 333.

[15] Withers H.R., Peters L.J., Taylor J.M.G.: “Dose-response relationship for radiation therapy of subclinical disease”. Int. J. Radiat. Oncol. Biol. Phys., 1995, 31, 353.

[16] Potish R., Downey G., Adcock L., Prem K., Twiggs L.: “The role of surgical debulking in cancer of the uterine cervix”. Int. J. Radiat. Oncol. Biol. Phys., 1989, 17, 979.

[17] Keys H., Bundy BN., Stehman F., Muderspach L.I., Chafe W.E., Suggs C.L., et al.: “Cisplatin, Radiation, and Adjuvant Hysterectomy Compared with Radiation and Adjuvant Hysterectomy for Bukly Stage IB Cervical Carcinoma”. N. Engl. J. Med., 1999, 340, 1154.

[18] Morris M., Eifel P.J., Lu J., Grigsby P.W., Levenback C., Stevens R.E., et al.: “Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer”. N. Engl. J. Med., 1999, 340, 1137.

[19] Rose P.G., Bundy B.N., Watkins E.B., Thigpen J.T., Deppe G., Maiman M.A., et al.: “Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervixl Cancer”. N. Engl. J. Med., 1999, 340, 1144.

[20] Whitney C.W, Sause W., Bundy B.N., Malfetano J.H., Hannigan E.V., Fowler W.C., et al.: “Randomized Comparison of Fluorouracil Plus Cisplatin Versus Hydroxyurea as an Adjunct to Radiation Ther- apy in Stage IIB-IVA Carcinoma of the Cervix With Negative Para-Aortic Lymph Nodes: A Gynecologic Oncology Group and Southwest Oncology Group Study”. J. Clin. Oncol., 1999, 17, 1339.

[21] Cheung T.H., Lo K.W.K., Yim S.F., Yau S.H., Yu M.M.Y., Yeung W.K.: “Debulking metastatic pelvic nodes before radiotherapy in cervical cancer patients: A long-term follow-up result”. Int. J. Clin. Oncol., 2011, 16, 546.

[22] Kupets R., Thomas G.M., Covens A.: “Is there a role for pelvic lymph node debulking in advanced cervical cancer?” Gynecol. Oncol., 2002, 87, 163.

[23] Tammela J., Bundy B., Odunsi K.: “Reassessment of pelvic lymph node debulking in advanced cervical cancer”. Gynecol. Oncol., 2004, 92, 1014.

[24] STROBE: “STROBE statement—checklist of items that should be included in reports of observational studies”. November, 2007. Available at: https://www.strobe-statement.org/index.php?id=available-checklists

[25] Cervical Cancer: “National Comprehensive Cancer Network. October 10, 2016”. Available at: https://www.nccn.org/professionals/ physician_gls/pdf/cervical.pdf

[26] Varia M.A., Bundy B., Deppe G., Mannel R., Averette H., Rose P., Connelly P.: “Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study”. Int.J. Radiat. Oncol. Biol. Phys., 1998, 42, 1015.

[27] Yap M.L., Cuartero J., Yan J., Pintilie M., Fyles A., Levin M., et al.: “The role of elective para-aortic lymph node irradiation in patients with locally advanced cervical cancer”. Clin. Oncol. (R. Coll. Radiol.), 2014, 26, 797.

[28] Bipat S., Glas A.S., Van Der Velden J., Zwinderman A.H., Bossuyt P.M.M., Stoker J.: “Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: A systematic review”. Gynecol. Oncol., 2003, 91, 59.

[29] Boss E.A., Barentsz J.O., Massuger L.F.A.G., Boonstra H.: “Urogenital radiology Review article The role of MR imaging in invasive cervical carcinoma”. Eur. Radiol., 2000, 10, 256.

[30] Wright J.D., Dehdashti F., Herzog T.J., Mutch D.G., Huettner P.C., Rader J.S., et al.: “Preoperative lymph node staging of early-stage cervical carcinoma by [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography. Cancer, 2005, 104, 2484.

[31] Selman T.J., Mann C., Zamora J., Appleyard T.L., Khan K.: “Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis”. CMAJ, 2008, 178, 855.

[32] Choi H.J., Roh J.W., Seo S.S., Lee S., Kim J.Y., Kim S.K., et al.: “Comparison of the accuracy of magnetic resonance imaging and positron emission tomography/computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma: a prospective study”. Cancer, 2006, 106, 914.

[33] Loft A., Berthelsen A.K., Roed H., Ottosen C., Lundval L., Knudsen J., et al.: “The diagnostic value of PET/CT scanning in patients with cervical cancer: A prospective study”. Gynecol. Oncol., 2007, 106, 29.

[34] Leblanc E., Gauthier H., Querleu D., Ferron G., Zerdoud S., Morice P., et al.: “Accuracy of 18-fluoro-2-deoxy-D-glucose positron emission tomography in the pretherapeutic detection of occult para-aortic node involvement in patients with a locally advanced cervical carcinoma”. Ann. Surg. Oncol., 2011, 18, 2302.

[35] Ramirez P.T., Jhingran A., MacApinlac H.A., Eushcer E.D., Munsell M.F., Coleman R.L., et al.: “Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer”. Cancer, 2011, 117, 1928.

[36] Duenas-Gonzalez A., Zarba J.J., Patel F., Alcedo J.C., Beslija S., Casanova L., et al.: “Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix”. J. Clin. Oncol., 2011, 29, 1678.

[37] Cihoric N., Tapia C., Kruger K., Aebersold D.M., Kaleser B., Lossl K.: “IMRT with 18 FDG-PET\CT based simultaneous integrated boost for treatement of nodal positive cervical cancer”. Radiat.Oncol., 2014, 9, 83.

[38] Shumway J.W., Echeverria A.E., Patel U., Asper J., Bonnen M., Ludwig M.: “Effectiveness of intensity-modulated radiation therapy with simultaneous integrated boost in cervical cancer patients with PET positive lymph nodes”. J. Radiat. Oncol., 2017, 6, 167.