Neoadjuvant chemotherapy, radical hysterectomy and chemoradiation for stage iva cervical carcinoma

Despite the efficacy of chemotherapy and radiotherapy in the management of locally advanced cervical carcinoma, the overall survival rates are relatively inauspicious. We recount a case involving a 56-year-old stage IVA cervical cancer patient who underwent neoadjuvant chemotherapy, a type V radical hysterectomy and adjuvant chemoradiation in April 2006. The patient remained in clinical remission for five years until she developed a metastatic pulmonary nodule in her right middle lobe that originated from the primary cervical cancer. Thereafter, the patient was diagnosed with a right metastatic cardiophrenic nodule that responded favorably to chemotherapy. However, in August 2014, she presented with a metastatic posterior cranial fossa tumor from which she ultimately expired; interestingly, radiologic imaging revealed no evidence of an abdominopelvic recurrence. While a radical hysterectomy is often indicated for advanced cervical cancer patients with residual disease or those who fail chemoradiation, perhaps in select cases (e.g., stage IVA disease), initial treatment with neoadjuvant chemotherapy and surgery followed by chemoradiation may improve patient survival.

Cervical cancer; Radical hysterectomy; Chemoradiation; Outcomes.

[1] Siegel R.L., Miller K.D., Jemal A.: “Cancer statistics, 2018”. CA Cancer J. Clin., 2018; 68, 7-30.

[2] Razzaghi H., Epidemic Intelligence Service Program, Centers for Disease Control and Prevention; Atlanta Georgia, Saraiya M., Thompson T.D., Henley S.J., Viens L., et al.: “Five-year relative survival for human papillomavirus-associated cancer sites”. Cancer, 2018, 124, 203-211.

[3] Monk B.J., Sill M.W., McMeekin D.S., Cohn D.E., Ramondetta L. M., Boardman C.H., et al.: “Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study”. J. Clin. Oncol., 2009, 27, 4649-4655.

[4] Rosen V.M., Guerra I., McCormack M., Nogueira-Rodrigues A., Sasse A., Munk V.C. et al.: “Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab-Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer”. Int. J. Gynecol., 2018, 27, 1237-1246.

[5] Sebastião A.M., da Silva Rocha L.S., Gimenez R.D., de Barros L. A.B., Fukushima J.T., da Silva S.C.S., et al.: “Carboplatin-based chemoradiotherapy in advanced cervical cancer: an alternative to cisplatin-based regimen?”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2017, 201, 161-165.

[6] Lèguevaque P., Motton S., Delannes M., Querleu D., Soulé-Tholy M., Tap G., et al.: “Completion surgery or not after concurrent chemoradiotherapy for locally advanced cervical cancer?”. Eur. J. Obstet. Gynecol. Rep. Biol., 2011, 155, 188-192.

[7] Classe J.M., Rauch P., Rodier J.F., Morice P., Stoeckle E., Lasry S., et al.: “Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: Morbidity and outcome: Results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer)”. Gynecol. Oncol., 2006, 102, 523-529.

[8] Ferrandina G., Margariti P.A., Smaniotto D., Petrillo M., Salerno M. G., Fagotti A., et al.: “Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients admin-istered concomitant chemoradiation followed by radical surgery”. Gynecol. Oncol., 2010, 119, 404-410.

[9] Touboul C., Uzan C., Mauguen A., Gouy S., Rey A., Pautier P., et al.: “Prognostic Factors and Morbidities After Completion Surgery in Patients Undergoing Initial Chemoradiation Therapy for Locally Advanced Cervical Cancer”. the Oncologist, 2010, 15, 405-415.

[10] Wakatsuki M., Kato S., Kiyohara H., Ohno T., Karasawa K., Tamaki T., et al.: “The prognostic value of rectal invasion for stage IVA uterine cervical cancer treated with radiation therapy”. Bmc. Cancer, 2016, 16, 244.

[11] Platt S.L., Patel A., Humphrey P.J., Al-Booz H.and Bailey J.: “Completion surgery after chemoradiotherapy for cervical cancer– is there a role? UK Cancer Centre experience of hysterectomy post chemoradiotherapy treatment for cervical cancer”. J. Obstet. Gynaecol., 2019, 39, 68-73.

[12] Vale C., Tierney J.F., Stewart L.A., Brady M., Dinshaw K., Jakobsen A., et al.: “Reducing uncertainties about the effects of chemoradio-therapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials”. J. Clin. Oncol., 2009, 26, 5802-5812.

[13] Marin F., Plesca M., Bordea C.I., Moga M.A., Blidaru A.: “Types of radical hysterectomies : From Thoma Ionescu and Wertheim to present day”. J. Med. Life, 2015, 7, 172-176.

[14] Benedetti Panici P., Bellati F., Manci N., Pernice M., Plotti F., Di Donato V., et al.: “Neoadjuvant Chemotherapy Followed by Radical Surgery in Patients Affected by FIGO Stage IVA Cervical Cancer”. Ann. Surg. Oncol., 2007, 14, 2643-2648.

[15] Gallotta V., Chiantera V., Conte C., Vizzielli G., Fagotti A., Nero C., et al.: “Robotic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study”. J. Minim. Invasive Gynecol., 2017, 24, 133-139.

[16] Ferrandina G., Gambacorta A., Gallotta V., Smaniotto D., Fagotti A., Tagliaferri L., et al.: “Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study”. Int.

[17] Ferrandina G., Palluzzi E., Gallotta V., Gambacorta M.A., Autorino R., Turco L.C., et al.: “Neoadjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study”. Eur. J. Surg. Oncol., 2018, 44, 1062-1068.

[18] Fanfani F., Vizza E., Landoni F., de Iaco P., Ferrandina G., Cor-rado G., et al.: “Radical hysterectomy after chemoradiation in FIGO stage III cervical cancer patients versus chemoradiation and brachytherapy: Complications and 3-years survival”. Eur. J. Surg. Oncol., 2016, 42, 1519-1525.

[19] Keys H.M., Bundy B.N., Stehman F.B., Muderspach L.I., Chafe W. E., Suggs C.L., 3rd. et al.: “Cisplatin, radiation and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage”. IB cervical carcinoma. NEJM., 1999, 340, 1154-1161.

[20] Zigras T., Lennox G., Willows K. Covens A.: “Early Cervical Cancer: Current Dilemmas of Staging and Surgery”. Curr. Oncol. Rep., 2017, 19, 51.

[21] Marchetti C., De Felice F., Di Pinto A., Romito A., Musella A., Palaia I., et al. Marchetti C., De Felice F., Di Pinto A., Romito A., Musella A., Palaia I., et al.: “Survival Nomograms after Curative Neoadjuvant Chemotherapy and Radical Surgery for Stage IB2-IIIB Cervical Cancer”. Cancer Res. Treat., 2018, 50, 768-776.

[22] Lorusso D., Petrelli F., Coinu A., Raspagliesi F. Barni S.: “A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer”. Gynecol. Oncol., 2014, 133, 117-123.

[23] Kitagawa R., Katsumata N., Shibata T., Kamura T., Kasamatsu T., Nakanishi T., Nishimura S., et al.: “Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505”. J. Clin. Oncol., 2015, 33, 2129-2135.

[24] Micha J. P., Sassoon A.F., Wong H. and Goldstein B.H.: “Prolonged remission of recurrent cervical carcinoma following paclitaxel and carboplatin chemotherapy with paclitaxel maintenance chemotherapy”. Anticancer. Drugs, 2015, 26, 793-796.

[25] Giavedoni M.E., Staringer L., Garrido R., Bertoncini C., Sardi M., Perrotta M. et al.: “Experience with concurrent chemoradiotherapy treatment in advanced cervical cancer: results from a hospital in Argentina”. Ecancermedicalscience, 2019, 13, 919.

[26] Abaid L.N., Micha J.P., Rettenmaier M.A., Brown J.V., Mendivil A.A., Lopez K.L., et al.: “A phase II study of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage primary epithelial ovarian, fallopian tube, or peri-toneal carcinoma”. Cancer Chemother. Pharmacol., 2013, 72, 101-107.

[27] Rose P.G., Java J., Whitney C.W., Stehman F.B., Lanciano R., Thomas G.M., et al.: “Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG OncologyGynecologic Oncology Group Randomized Trials of Chemoradiotherapy”. J. Clin. Oncol., 2015, 33, 2136-2142.

[28] Micha J.P., Brown J.V.: “Primary Surgical Cure of Stage III-B Cer-vical Carcinoma with Adnexal Metastasis”. Gynecol. Oncol., 1998, 71, 317-319.

[29] Matsuo K., Mandelbaum R.S., Adams C.L., Roman L.D.and Wright J. D.: “Performance and outcome of pelvic exenteration for gynecologic malignancies: A population-based study”. Gynecol. Oncol., 2019, 153, 368-375.