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Originally published as JCO Early Release 10.1200/JCO.2009.21.8255 on March 23 2009 © 2009 American Society of Clinical Oncology.
Reply to P. Morice et alCancer Registry of Norway, Oslo, Norway
Dept. of Clinical Cancer Research, Division of Cancer Medicine and Radiotherapy, Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello; Faculty Division the Norwegian Radium Hospital, University of Oslo, Oslo, Norway We appreciate the opportunity to respond to thoughtful comments by Morice et al1 regarding our recent article in Journal of Clinical Oncology.2 Morice et al1 note there was a relatively high number of patients with cervical and ovarian cancer having postcancer pregnancies in our data. We believe there may be several explanations for this. During the study period, conservative, fertility-preserving surgery was introduced for selected women with stage I cervical or ovarian cancer tumors. However, we observed a few women undergoing similar surgery before the procedure was standardized. All patients included in the analyses had histologically verified malignancies. Of the ovarian cancers, there were 29 epithelial and 39 nonepithelial. Among the cervical cancers, there were 78 adenocarcinomas and 107 squamous cell carcinomas. Most of these were small tumors, in general micro-invasive disease (stage Ia), and often seen together with histology consistent with borderline ovarian or cervical intraepithelial neoplasia III tumors. Whereas these tumors are registered as malignancies, treatment is limited as in the case of premalignant tumors to conization or unilateral salpingo-oophorectomy with preservation of the contra-lateral ovary and uterus. The data used in our study is generated in the same manner as the numbers used in Cancer in Norway, an annual publication covering cancer incidence, prevalence, and mortality in the Norwegian population.3 The file is derived from the main database in the Cancer Registry, including all new invasive cancer cases in the period studied. Carcinoma in situ of the uterine cervix and borderline tumors of the ovary are not included. Preservation of reproductive function in fertile women who not have completed family planning is important, if the staging and risk profile allows it. Most women in our cohort have been treated at the Norwegian Radium Hospital (Oslo, Norway). Conservative treatment for cervical and ovarian cancers of low stage and low risk has been offered to selected young women systematically since 1995 in Norway. However, already in 1987, women with epithelial ovarian cancers underwent conservative surgery at the Norwegian Radium Hospital, and women with nonepithelial cancers had that opportunity even earlier. Patients with cervical cancer at stage Ia1 (micro-invasive disease) were treated with conization since 1987; and from 1992, trachelectomy with pelvic lymphadenctomy was introduced (C.G. Trope, personal communication, January 2009). Besides the fact that most women in our study had micro-invasive disease, there was a considerably long median observation time (> 12 years) compared with Maneo et al4 (5.75 years) and most other studies in this area. This could have resulted in an increased number of women having postcancer pregnancies. The completeness of the registry-based information about new cancer cases and pregnancies is regarded as nearly 100% (overall completeness, 99.7%), and the loss to follow-up due to emigration is insignificant in our population (< 0.3%).5,6 Our article focused on the coincidence of pregnancy and cancer, with survival as the end point.2 Our next article (in preparation) will be focusing on reproduction rates for cancer survivors compared with the general population. The different histological types will be considered in subanalyses in that article to further address differences in prognosis. Regarding the comment about recurrence in persons with cervical and hematological cancer, we never considered postcancer pregnancies as a positive prognostic factor. The survival analyses reveals an 80% lower risk of cause-specific death among those patients, but the most appropriate interpretation would be that a self-selection among women with good prognosis and no recurrence resulted in the choice of becoming pregnant after cancer and cancer treatment. This is also described in the article as "the healthy mother effect."2 The analyses are performed with a time-dependent variable to take into account the time variance from the time of diagnosis to the time of becoming pregnant, respectively, to the time of death. This is described under sections Patient Selection and File Construction and Statistics.2 Lastly, we would like to express our support for the establishment of national guidelines such as those that Morice et al1 are presently proposing for patients with cervical, breast, or ovarian cancer diagnosed during pregnancy. As they mention, we strongly support a multidisciplinary team approach in such challenging clinical situations, to give the women affected and their unborn fetuses the best possible treatments and future prospects. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Morice P, Uzan C, Gouy S, et al: Cancer during pregnancy: The time has come for a prospective program. J Clin Oncol doi: 10.1200/JCO.2008.21.6192. 2. Stensheim H, Møller B, van Dijk T, et al: Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: A registry-based study. J Clin Oncol 27:45–51, 2009. 3. Institute of Population-Based Cancer Research. Cancer in Norway 2004. Oslo: Cancer Registry of Norway, 2005. p.22–24. 4. Maneo A, Chiari S, Bonazzi C, et al: Neoadjuvant chemotherapy and conservative surgery for stage IB1 cervical cancer. Gynecol Oncol 111:438–443, 2008.[CrossRef][Medline] 5. Statistics Norway: Population statistics. Immigration and emigration, 2007. http://www.ssb.no/english/subjects/02/02/20/innvutv_en/. 6. Institute of Population-Based Cancer Research. Cancer in Norway 2006: Erratum/special issue. Oslo: Cancer Registry of Norway, 2007, pp S17-S37. http://www.kreftregisteret.no/en/General/Publications/Cancer-in-Norway/Cancer-in-Norway-2006/.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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