A survival study of uterine cervical patients in the North East India: Hospital-cancer registry-based analysis

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Byline: Amal. Kataki, Jagannath. Sharma, Manigreeva. Krishnatreya, Nizara. Baishya, Debabrata. Barmon, Pankaj. Deka, Manoj. Kalita

Background: Uterine cervical cancer constitutes a major proportion of cancer in females of our population. The objective of this study was to conduct a clinical study of uterine cervical cancers including their survival from hospital-cancer registry data. Materials and Methods: Data of uterine cervical cancer patients diagnosed from January 1, 2010 to December 31, 2010 and that were treated at a regional cancer center in North East (NE) India was recruited. The cases were analyzed for age group distribution, stage, and treatment types. Survival from the date of first diagnosis and hazard ratios (HRs) was estimated. Survival probability and HRs were calculated by Kaplan-Meier method and Cox-proportional regression analysis, respectively. Active follow-up was done for the survival analysis. Results: One hundred and ninety-three patients (53.4%) were included for the analysis. Median age was 48 years, 56.5% (108/193) of patients were in the age group of 45-64 years, 56.5% (109/193) were Stage II patients, radiotherapy alone was the main treatment modality in 65.8% (127/193) of cases, 5-year overall survival (OS) was 40.7%, median survival was 44 months, early staged and advanced stage patients had 47.7%, and 29.4% 5-year OS (P = 0.002), respectively, and HR for advanced stages was 1.8 (P = 0.003, confidence interval (CI) = 1.2 to 2.7). Conclusion: Describing the clinical characteristics and survival of uterine cervical cancer patients is important for planning and identifying the gaps for its control in the NE India.

Introduction

Uterine cervix cancer is one of the leading causes of cancer deaths among women in the world, and it is a leading cause of cancers in females of low-middle income countries such as India.[1] Due to an effective screening program in the developed countries, the burden of uterine cervical cancers is on a decline in those countries. In India, uterine cervical cancers have the highest disease frequency with an estimated 1,34,000 new cases and 73,000 deaths each year.[2] The age adjusted incidence rates for uterine cervical cancers in India ranges from 5.6 per 100,000 populations to as high as 24.3 per 100,000 populations.[3]

Cancer of the uterine cervix is considered relatively as a fatal cancer. The 5-year survival in patients affected with uterine cervical cancers in low-middle income countries is poorer, especially when diagnosed in advanced stages. The late diagnosis of uterine cervical cancers in developing countries such as India can be attributed to fear and ignorance about this disease among all sections of women. Moreover, there is a lack of adequate facilities across the country for proper early diagnosis of uterine cervix cancers. A study in the Indian context has shown that with a proper approach, population-based screening programs are feasible in the country.[4] High level of illiteracy is an impediment toward effective control of uterine cervix cancer in our settings. Education of patients helps in the early detection of cancer patients.[5] Furthermore, a study in our settings has shown that a large proportion of patients with uterine cervix cancers were illiterates.[6]

Currently, there are no data that has shown the 5-year survival statistics of patients with uterine cervical cancers from the North East (NE) India. A nationwide multi-centric study has shown that on an annual basis, 38,771 patients with cervical cancers in the country do not get the benefit of required treatment and thus they have poorer survival.[7] Thus, it becomes imperative to understand the survival of uterine cancer patients treated in our settings, as it will help for planning and control of cancers of the uterine cervix in our population. In this study, we aimed to conduct a clinical study of uterine cervical cancers including 5-year survival analysis from the hospital-cancer registry data.

Materials and Methods

This study was conducted as part of Pattern of Care and Survival Studies, which has been approved by the Institutional Review Board of our institute. This was a retrospective single-centric study done on electronically recorded data obtained from the hospital-based cancer registry of a regional cancer center in the NE India. The hospital-cancer registry of our regional cancer center serves as one of the major sources of registration for NE population-based cancer registries. Patients with uterine cervical cancers which were diagnosed during the period from January 1, 2010 to December 31, 2010 were considered for the present study. The cases of uterine cervix cancer were identified in the registry database by the International Statistical Coding for Disease-10th revision coding (C.53). The cases were evaluated for median age and age groups, stage at diagnosis, and treatments received. Median and 5-year overall survival (OS) was estimated from the date of first diagnosis (DOFD), and hazard ratios (HRs) were calculated. The patients in the study cohort were staged according to the International Federation of Gynecology and Obstetrics staging system. The treatment categories in the study were surgery, radiotherapy (RT), RT + chemotherapy (RT + CT), and surgery followed by RT. The data were categorical except for age of the patients. Follow-up for survival analysis was active.

Patient follow-up

The closing period of patient follow-up was 60 months or 5-year from DOFD. The last date of patient follow-up was first recorded from the patient case sheets. Information on death was then searched in the hospital mortality records by matching the unique hospital identification number allotted to each patient at the time of registration and in cases where vital status information of the patients could not be obtained from hospital visits and mortality records till the closing period of the study, telephonic calls were made to the phone numbers which were provided at the time of patient registration. Moreover, in cases where the patient follow-up was not complete till 5-year, the day of last hospital visit was noted as censored date. The demographic follow-up or telephonic follow-up was carried out by trained medical social workers.

Statistical analysis

Kaplan-Meier estimate was used to predict the survival probabilities of the patients and survival was also estimated as median survival function. The test was conducted at 95% confidence interval (95% CI), and P < 0.05 was considered statistically significant. The survival differences were statistically compared by log-rank test. Cox-proportional regression analysis for estimating the HR was done after adjusting for age of the patients. Statistical Package for Social Sciences (SPSS) version 17.0 (International Business Machines Corp., Chicago, IL, USA) was used for the present analysis.

Results

A total of 361 uterine cervix cancer patients were diagnosed during the study period. Out of 361 patients, 193 patients (53.4%) had information on stage and treatments in our present data base. Hence, the final data set for analysis consisted of information on 193 patients. Median age of patients was 48 years (range = 25-91 years). Sixty-five (33.7%) patients were in the age group of 45-54 years, 52 (26.9%) patients were in 35-44 years age group, in the age group of 55-64 there were 44 (22.8%) patients, 14 (7.3%) were in 65-74 years, 13 (6.7%) patients were <35 years, and 2.6% of patients were over 75 years of age [Figure 1].{Figure 1}

Stage at diagnosis and treatment types

The stage distribution in descending order was Stage II in 56.5% of patients, Stage III in 35.8% of patients, Stage I in 4.1% of patients, and in 7 (3.6%) patients the stage at diagnosis was Stage IV [Table 1]. Among treatment groups, 127 (65.8%) patients received RT, 63 (32.6%) patients received RT + CT, and two (1.0%) patients underwent surgery followed by RT as shown in [Table 1]. One (0.5%) patient was treated by surgery.{Table 1}

Survival estimates and hazards

On follow-up, 98 (50.8%) patients of the study cohort were dead at the closing period and 95 (49.2%) patients were either alive or censored at variable length of time from the DOFD. The median survival was 44 months (standard error = 6.6, 95% CI, 31.0-56.9). The 5-year cumulative OS was 40.7% [Figure 2]. The number of patients in Stage I and Stage IV was less. Hence, the patients in Stage I and Stage II were clubbed as early cases and patients in Stages III and IV as advanced cases. The median survival in early cases was 62 months and in advanced cases, the median survival was 32 months. The 5-year OS was higher in the early cases compared to advanced cases of uterine cervix cancers (47.7% vs. 29.4%, P = 0.002) as shown in [Figure 3]a. After adjusting for the age of patients, HR for advanced cases was 1.8, P = 0.003, CI = 1.2-2.7 [Table 2].{Figure 2}{Figure 3}{Table 2}

Radiotherapy and chemo-radiotherapy

The median survival in the RT group was 38 months, and in the RT + CT group, it was 57 months. The 5-year OS in the RT + CT and RT alone group was 39.1% and 38.9%, respectively ( P = 0.153) [Figure 3]b.

Discussion

Increasing age is an important risk factor in the development of uterine cervical cancers. In this study, the median age of treated patients was 48 years and the lower age limit was 25 years. The frequency of cytopathological abnormalities increases with age, and maximum frequency was observed in older women beyond 40 years of age.[8] In this study, 56.5% of all treated patients were in the age group of 45-64 years of age and 10% of all patients who underwent treatment were above 65 years of age.

In this analysis, majority (56.5%) of patients were diagnosed in Stage II disease. In our settings, patients in Stage II were mostly Stage IIB and in Stages III-IV, it was Stage IIIB. The proportion of Stage IV cancers were less than Stage I uterine cervical cancers in the present analysis. Clinical experience from our setting suggests that a majority of patients sought health care after many months since the appearance of clinical symptom of uterine cervical cancer.[9] This is the main attribute for advanced cases of uterine cervix. In addition, due to lack of a sustained and organized screening program in this part of the country, most of the patients with uterine cervical cancers presents at a fairly advanced stage of their diseases. Screening programs to include human papilloma virus testing along with cytological examinations is recommended as sensitive tool for primary screening of uterine cervical cancer.[10] The overall population-based relative survival declined from 66% to 61% in France between 1995-1999 and 2000-2004.[11] This was attributed to the removal of less aggressive tumors by more intensive cervical screening for preinvasive lesions.[12]

In our settings, RT was the main modality of treatment alone in 65.8% of cases and in combination with other forms in 99.5% of cases. A study has shown that definitive RT alone gives a complete response in 88% of cases with a recurrence rate of 30%.[13] The survival benefit due to chemoradiotherapy compared to RT alone is well established in uterine cervical cancers.[14],[15],[16],[17],[18] Our retrospective review has shown that in our settings, 32.6% of patients had received RT + CT. A nationwide study by Nandakumar et al. has shown that this scenario is reflected all across the country, as many patients would have been benefitted by addition of CT to RT.[7] Nonetheless, factors such as availability of resources, general health of the patients, and socioeconomic conditions limits the proportion of patients in the RT + CT group in comparison. Moreover, in early cases (Stage IB), surgery followed by adjuvant RT has shown to significantly increase disease free survival.[19] Thus, RT is the main modality alone or in combination. Moreover, every effort should be made to improve the access of patients with uterine cervical cancers to center where RT facilities are available.

This is the first study from the NE India that shows the 5-year survival of patients with uterine cervical cancers from this region. The 5-year OS in patients with uterine cervical cancers is wide ranging and depended upon the types of study. From observational studies to randomized-controlled trials, the 5-year OS ranged from 52% to 75%.[7],[18],[20] In this analysis, the 5-year OS was 40.7% with a median survival of 44 months, which was lower in the comparison. Furthermore, our study has revealed that the 5-year OS significantly improved from 29.4% to 47.7% ( P < 0.05) in patients who were diagnosed in early stages in comparison to advanced staged cases. It is known that patients with advanced uterine cervical cancers are more likely to die due their diseases. Our study has also shown that hazard of death in patients diagnosed in advanced stages was 1.8 times ( P < 0.05). Though in our present study, RT + CT showed better survival, but it was statistically not significant ( P > 0.05) and the number of patients in RT + CT and RT group were not comparable for a fair comparison.

There are certain limitations in this type of study, like the lack of data on disease statuses during follow-up, as the follow-up was mostly telephonic. Hence, the analysis was categorical with limited clinical utility. Furthermore, this was a retrospective analysis and there was a selection bias in the inclusion of patients for the analysis.

Conclusion

Our study has shown the survival of uterine cervical cancer patients treated in our settings, which was lower compared to more developed settings. And, this study showed that early diagnosis of uterine cervical cancers significantly improved the 5-year OS. Thus, population-based screening program for uterine cervical cancers should be implemented in our population for its better control.

Acknowledgment

The authors would like to thank the National Centre for Disease Informatics and Research under Indian Council of Medical Research for providing the necessary technical support to our hospital-cancer registry.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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