Prognostic significance of pathological response after neoadjuvant chemotherapy or chemoradiation for locally advanced cervical carcinoma

Myrna Candelaria, José Chanona-Vilchis, Lucely Cetina, Diana Flores-Estrada, Carlos López-Graniel, Aaron González-Enciso, David Cantú, Adela Poitevin, Lesbia Rivera, Jose Hinojosa, Jaime de la Garza, Alfonso Dueñas-Gonzalez, Myrna Candelaria, José Chanona-Vilchis, Lucely Cetina, Diana Flores-Estrada, Carlos López-Graniel, Aaron González-Enciso, David Cantú, Adela Poitevin, Lesbia Rivera, Jose Hinojosa, Jaime de la Garza, Alfonso Dueñas-Gonzalez

Abstract

Background: Cisplatin-based chemoradiation is the standard of care for locally advanced cervical cancer patients; however, neoadjuvant modalities are currently being tested. Neoadjuvant studies in several tumor types have underscored the prognostic significance of pathological response for survival; however there is a paucity of studies in cervical cancer investigating this issue.

Methods: Four cohorts of patients with locally advanced cervical carcinoma (stages IB2-IIIB); included prospectively in phase II protocols of either neoadjuvant chemotherapy with 1) cisplatin-gemcitabine, 2) oxaliplatin-gemcitabine, 3) carboplatin-paclitaxel or 4) chemoradiation with cisplatin or cisplatin-gemcitabine followed by radical hysterectomy were analyzed for pathological response and survival.

Results: One-hundred and fifty three (86%) of the 178 patients treated within these trials, underwent radical hysterectomy and were analyzed. Overall, the mean age was 44.7 and almost two-thirds were FIGO stage IIB. Pathological response rates were as follows: Complete (pCR) in 60 cases (39.2%), Near-complete (p-Near-CR) in 24 (15.6 %) and partial (pPR) in 69 cases (45.1%). A higher proportion rate of pCR was observed in patients treated with chemoradiotherapy (with cisplatin [19/40, 47.5%]; or with cisplatin-gemcitabine [24/41, 58.5%] compared with patients receiving only chemotherapy, 6/23 (26%), 3/8 (37.5%) and 8/41 (19.5%) for cisplatin-gemcitabine, oxaliplatin-gemcitabine and carboplatin-paclitaxel respectively [p = 0.0001]). A total of 29 relapses (18.9%) were documented. The pathological response was the only factor influencing on relapse, since only 4/60 (6.6%) patients with pCR relapsed, compared with 25/93 (26.8%) patients with viable tumor, either pNear-CR or pPR (p = 0.001). Overall survival was 98.3% in patients with pCR versus 83% for patients with either pNear-CR or pPR (p = 0.009).

Conclusion: Complete pathological response but no Near-complete and partial responses is associated with longer survival in cervical cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

Figures

Figure 1
Figure 1
(A) Overall survival according to type of response. At a median follow-up time of 29.6 months (2.9–66.4), the survival for complete pathological response is 98.3% whereas is 83% for those with near-complete and partial response, (p = 0.009). (B) Overall survival for those with a response less than complete (near-complete and partial response). The survival for near-complete is 83.3% whereas is 82.3% for those with partial response (p = 0.820).

References

    1. Mohar A, Frias-Mendivil M. Epidemiology of cervical cancer. Cancer Invest. 2000;18:584–590.
    1. Peters WA, 3rd, Liu PY, Barrett R, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W, Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18:1606–1613.
    1. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gerhenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. New Engl J Med. 1999;340:1137–1143. doi: 10.1056/NEJM199904153401501.
    1. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL, Walker JL, Gersell D. A comparison of weekly cisplatin during radiation therapy versus irradiation alone each followed by adjuvant hysterectomy in bulky stage IB cervical carcinoma: a randomized trial of the Gynecology Oncology Group. New Engl J Med. 1999;340:1154–1161. doi: 10.1056/NEJM199904153401503.
    1. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalacos S. Concurrent cisplatin-based chemoradiation improves progression-free survival in advanced cervical cancer: results of a randomized Gynecologic Oncology Group study. New Engl J Med. 1999;340:1144–1153. doi: 10.1056/NEJM199904153401502.
    1. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC, Jr, Clarke-Pearson DL, Liao SY. A randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stages 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;17:1339–1348.
    1. Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: A systematic review and meta-analysis. Lancet. 2001;358:781–786. doi: 10.1016/S0140-6736(01)05965-7.
    1. Neoadjuvant chemotherapy for cervical cancer meta-analysis collaboration Neoadjuvant chemotherapy for locally advanced cervix cancer: a systematic review and meta-analysis of individual patient data from 21 randomized controlled trials. Eur J Cancer. 2003;39:2470–2486. doi: 10.1016/S0959-8049(03)00425-8.
    1. Duenas-Gonzalez A, Cetina L, Mariscal I, de la Garza J. Modern management of locally advanced cervical carcinoma. Cancer Treat Rev. 2003;29:389–399. doi: 10.1016/S0305-7372(03)00068-9.
    1. Stebbing JJ, Gaya A. The evidence-based use of induction chemotherapy in breast cancer. Breast Cancer. 2001;8:23–37.
    1. Kurosumi M. Significance of histopathological evaluation in primary therapy for breast cancer – recent trends in primary modality with pathological complete response (pCR) as endpoint. Breast Cancer. 2004;11:139–47.
    1. Dueñas-Gonzalez A, Lopez-Graniel C, González A, Reyes M, Mota A, Muñoz D, Solorza G, Hinojosa LM, Guadarrama R, Florentino R, Mohar A, Melendez J, Maldonado V, Chanona J, Robles E, De la Garza J. A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma. Ann Oncol. 2001;12:541–547. doi: 10.1023/A:1011117617514.
    1. Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez A, Gomez E, Rivera L, Mohar A, Chanona G, Trejo-Becerril C, de la Garza J. Induction chemotherapy with gemcitabine and oxaliplatin for locally advanced cervical carcinoma. Am J Clin Oncol. 2003;26:22–25. doi: 10.1097/00000421-200302000-00005.
    1. Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez-Enciso A, Cetina L, Rivera L, Mariscal I, Montalvo G, Gómez E, De la Garza J, Chanona G, Mohar A. A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation. Ann Oncol. 2003;14:1278–84. doi: 10.1093/annonc/mdg333.
    1. Duenas-Gonzalez A, Cetina-Perez L, Lopez-Graniel C, Gonzalez-Enciso A, Gomez-Gonzalez E, Rivera-Rubi L, Montalvo-Esquivel G, Munoz-Gonzalez D, Robles-Flores J, Vazquez-Govea E, de La Garza J, Mohar A. Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: a randomized phase II study. Int J Radiat Oncol Biol Phys. 2005;61:817–823. doi: 10.1016/j.ijrobp.2004.07.676.
    1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481.
    1. Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187–220.
    1. Cetina L, Rivera L, Hinojosa J, Poitevin A, Uribe J, Lopez-Graniel C, Cantu D, Candelaria M, de la Garza J, Duenas-Gonzalez A. The routine management of locally advanced cervical cancer with concurrent radiation and cisplatin, five-year results. BMC Women's Health. 2006;6:3. doi: 10.1186/1472-6874-6-3.
    1. Chang TC, Lai CH, Hong JH, Hsueh S, Huang KG, Chou HH, Tseng CJ, Tsai CS, Chang JT, Lin CT, Chang HH, Chao PJ, Ng KK, Tang SG, Soong YK. Preliminary results of concurrent radiotherapy and chemotherapy with cis-platinum, vincristine and bleomycin in bulky, advanced cervical carcinoma. A pilot study. Gynecol oncol. 1992;44:182–188. doi: 10.1016/0090-8258(92)90036-I.
    1. Singh KC, Agarwal A, Agarwal S, Rajaram S, Goel N, Agarwal N. "Quick Course" neoadjuvant chemotherapy with cisplatin, bleomycin and vincristine in advanced cervical cancer. Gynecol Obstet Invest. 2004;58:109–113. doi: 10.1159/000078863.
    1. Porzio G, ficorella C, Toro G, Paris I, Recevuto E, Marchetti P. Short-term weekly neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer. Tumori. 2001;87:25–26.
    1. Kim DS, Moon H, Hwang YY, Cho SH. Preoperative adjuvant chemotherapy in the treatment of cervical cancer stage Ib, IIa, and IIb with bulky tumor. Gynecol Oncol. 1988;29:321–332. doi: 10.1016/0090-8258(88)90231-4.
    1. Benedetti Panici P, Scambia G, Greggi S, Di Roberto P, Baiocchi G, Mancuso S. Neoadjuvant chemotherapy and radical surgery in locally advanced cervical carcinoma: a pilot study. Obstet Gynecol. 1988;71:344–348.
    1. Lacava JA, Leone BA, Machiavelli M, Romero AO, Perez JE, Elem YL, Ferreyra R, Focaccia G, Suttora G, Salvadori MA, Cuevas MA, Acuna LR, Acuna JR, Langhi M, Amato S, Castaldi J, Arroyo A, Vallejo CT. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma. J Clin Oncol. 1997;15:604–609.
    1. Zanetta G, Lissoni A, Pellegrino A, Sessa C, Colombo N, Gueli-Alletti D, Mangioni C. Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer. Ann Oncol. 1998;9:977–980. doi: 10.1023/A:1008461408626.
    1. Sugiyama T, Nishida T, Kumagai S, Nishio S, Fujiyoshi K, Okura N, Yakushiji M, Hiura M, Umesaki N. Combination therapy with irinotecan and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer. Br J Cancer. 1999;81:95–98. doi: 10.1038/sj.bjc.6690656.
    1. Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez-Enciso A, Mohar A, Rivera L, Mota A, Guadarrama R, Chanona G, De la Garza J. Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced cervical carcinoma. Results from two consecutive phase II trials. Ann Oncol. 2002;13:1212–1219. doi: 10.1093/annonc/mdf196.
    1. Duenas-Gonzalez A, Lopez-Graniel CM, Mota A, Mohar A. Neoadjuvant chemotherapy followed by surgery in locally advanced cervical carcinoma. J Clin Oncol. 2002;20:2908–2909.
    1. Buda A, Fossati R, Colombo N, Fei F, Floriani I, Gueli Alletti D, Katsaros D, Landoni F, Lissoni A, Malzoni C, Sartori E, Scollo P, Torri V, Zola P, Mangioni C. Randomized trial of neoadjuvant chemotherapy comparing paclitaxel, ifosfamide, and cisplatin with ifosfamide and cisplatin followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the SNAP01 (Studio Neo-Adjuvante Portio) Italian Collaborative Study. J Clin Oncol. 2005;23:4137–4145. doi: 10.1200/JCO.2005.04.172.
    1. Resbeut M, Cowen D, Viens P, Noirclerc m, Perez T, Gouvernet J, Delpero JR, Gamerre M, Boubli L, Houvenaeghel G. Concomitant chemoradiation prior to surgery in the treatment of advanced cervical carcinoma. Gynecol Oncol. 1994;54:68–75. doi: 10.1006/gyno.1994.1168.
    1. Jurado M, Martinez-Monge R, Garcia-Foncillas J, Azinovic I, Aristu J, Lopez-Garcia G, Brugarolas A. Pilot study of concurrent cisplatin, 5-fluorouracil, and external beam radiotherapy prior to radical surgery +/- intraoperative electron beam radiotherapy in locally advanced cervical cancer. Gynecol Oncol. 1999;74:30–37. doi: 10.1006/gyno.1999.5424.
    1. Mancuso S, Smaniotto D, Benedetti-Panici P, Favale B, Greggi S, Manfredi R, Margariti PA, Morganti AG, Scambia G, Tortoreto F, Valentini V, Cellini N. Phase I-II trial of preoperative chemoradiation in locally advanced cervical carcinoma. Gynecol Oncol. 2000;78:324–328. doi: 10.1006/gyno.2000.5862.
    1. Lopez-Graniel C, Dolores R, Cetina L, Gonzalez A, Cantu D, Chanona J, Uribe J, Candelaria M, Brom R, de la Garza J, Duenas-Gonzalez A. Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer. BMC Cancer. 2005;5:118. doi: 10.1186/1471-2407-5-118.
    1. Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, O'Donoghue DP, Moriarty M, Fennelly D, Sheahan K. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47:141–146. doi: 10.1111/j.1365-2559.2005.02176.x.
    1. Trodella L, Granone P, Valente S, Margaritora S, Macis G, Cesario A, D'Angelillo RM, Valentini V, Corbo GM, Porziella V, Ramella S, Tonini G, Galetta D, Ciresa M, Vincenzi B, Cellini N. Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging. Ann Oncol. 2004;15:389–398. doi: 10.1093/annonc/mdh099.
    1. Splinter TA, Scher HI, Denis L, Bukowski R, Simon S, Klimberg I, Soloway M, Vogelzang NJ, van Tinteren H, Herr H. The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer – Genitourinary Group. J Urol. 1992;147:606–608.
    1. Chollet P, Amat S, Cure H, de Latour M, Le Bouedec G, Mouret-Reynier MA, Ferriere JP, Achard JL, Dauplat J, Penault-Llorca F. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer. 2002;86:1041–1046. doi: 10.1038/sj.bjc.6600210.
    1. Brain E, Garrino C, Misset JL, Carbonero IG, Itzhaki M, Cvitkovic E, Goldschmidt E, Burki F, Regensberg C, Pappo E, Hagipantelli R, Musset M. Long-term prognostic and predictive factors in 107 stage II/III breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy. Br J Cancer. 1997;75:1360–1367.
    1. Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR. Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2004;91:2012–2017. doi: 10.1038/sj.bjc.6602235.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere