Clinical Investigation
Long-Term Outcome and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinoma of Cervix After Definitive Radiotherapy

https://doi.org/10.1016/j.ijrobp.2010.02.009Get rights and content

Purpose

To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery.

Methods and Materials

A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed.

Results

The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease.

Conclusion

Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease.

Introduction

Adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix are relatively uncommon histologic subtypes of cervical cancer. The incidence of cervical cancer has decreased during the past 40 years with the introduction of Papanicolaou smear screening. However, recently, the absolute incidence rate of AC/ASC and its relative proportion compared with squamous cell carcinoma (SCC) have increased in many countries 1, 2. In general, patients with AC/ASC undergo the same first-line treatment as those with SCC. However, it remains uncertain whether AC/ASC patients have a worse prognosis than those with SCC and whether they should follow the same treatment strategy. In some reports, patients' survival for both histologic subtypes were similar 3, 4. However, in others, the AC/ASC patients had worse outcomes 5, 6, 7. Despite the analysis and publication of various prognostic factors for AC/ASC, those related to the outcome of patients primarily treated with radiotherapy (RT) are not well established, because many studies included heterogeneous patient populations, were published in early eras, or had small case numbers. Because RT is a major treatment modality for AC/ASC of the cervix, it is necessary to clarify these issues using on a larger patient population.

We have previously reported the patient characteristics and treatment results for 53 AC/ASC patients primarily treated with RT between 1990 and 1996. We found that our AC/ASC patients had worse survival rates and inferior local control compared with those with SCC (7). In the present study, we extended our analysis to a larger population of 148 AC/ASC patients primarily treated with RT between 1990 and 2004. The increase in case numbers should enable us to better identify the prognostic factors and determine the salvage rate by surgery for selected patients with local failure. Furthermore, concurrent chemoradiotherapy (CCRT) was not a common practice at the time of our previous report but has become standard treatment since 1999. We therefore tried to analyze the efficacy of CCRT for AC/ASC. The present study, although it was a retrospective analysis, included a relatively large series and might help us understand the clinical behavior of AC/ASC, the response to RT/CCRT, and provide useful information for designing appropriate treatment strategies.

Section snippets

Patients and staging workup

Between 1990 and 2004, 158 patients with International Federation of Gynecology and Obstetrics Stage I-IVA AC/ASC of the cervix primarily underwent RT at Chang Gung Memorial Hospital (Lin-Kou, Taiwan). Only 148 patients who completed the full RT course were included in the present study. For Stage IB and IIA, bulky tumor was defined as a tumor diameter >4 cm by clinical palpation. The staging workup included the usual radiographs, laboratory analysis, and computed tomography/magnetic resonance

Patient characteristics

Of the 148 patients, 90 (61%) had AC and 58 had ASC. The distribution of clinical parameters and treatment-related variables is listed in Table 1 and 2, respectively. The median age was 54 years (range, 32–89), 8 years younger than our patients with SCC who were primarily treated with RT (8). The percentage of well/moderately differentiated histologic features was greater for AC patients (62%) than for ASC patients (28%). Most (76%) patients had Stage IB-IIA bulky or greater disease. Elevation

Discussion

Patients with AC/ASC of the cervix have been reported to have a worse prognosis than those with SCC 5, 7. The present updated report of 148 AC/ASC patients has provided additional confirmation. The difference in the 5-year RFS rates between the SCC and AC/ASC patients was 20–35% and was statistically significant in a stage-by-stage comparison. The survival rate of patients with SCC in the present updated analysis was similar to that of our previous reports 7, 8, suggesting the reproducibility

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