Distribution of patients with respect to age, stage, and histopathological differentiation

Age of patients ranged from 30 to 75 years with a mean value of 49.74 ± 11.19 years, 80 (47.9%) patients had Stage II and 87 (52.1%) had Stage III disease. All the patients had squamous cell histology with 85 (50.9%) having WD, 76 (45.5%) MD, and 6 (3.6%) PD histopathology.

Association of histopathological differentiation with age and stage of the patients

Majority of subjects (51.4%) aged <60>60 years were observed to be having MD histopathology (52%), but no significant association between age and histopathological differentiation was observed (P = 0.502). No significant association between stage and histopathological differentiation was also observed (P = 0.289).

Treatment outcome of the patients after receiving radical chemo-radiotherapy with median follow-up of 11 months

Of the 167 patients treated, 133 (79.6%) had a complete response and 34 (20.4%) had residual disease. Nineteen patients developed local recurrence and five patients had a distant relapse in a median follow-up of 11 months. The pattern of residual and recurrences cases is shown in the [Table 4] and [Table 5]. The distant relapse in PD group was seen in two patients out of six (33.3%) as compared with WD group which was seen in 1 out of 85 (1.17%) patients and MD group which was seen in 2 out of 76 (2.63%) which was significantly more, P = 0.025 (Fisher's exact test) and P = 0.011 (Fisher's exact test), respectively, and among patients with Stage III disease, 4 out of 87 (4.6%) developed distant relapse, whereas in Stage II, only 1 out of 80 (1.25%) had distant relapse. Local recurrence in MD group 9/76 (11.84%) and WD group 10/85 (11.75%) is similar, but local recurrence in Stage III disease (13/87 [14.95%]) is twice that of Stage II 6/80 (7.5%).

Comparing the residual pattern of disease with respect to stage and histopathological differentiation

Comparing the recurrence pattern of disease with respect to stage and histopathological differentiation

Treatment outcome association with age, stage, and histopathologic grading has been given in [Table 6].

Association of treatment response with stage of the disease, histopathological differentiation, and age of patients

Treatment outcome in relation to age, stage, and histopathological examination has shown no statistically significant relation; however, Stage II patients have better treatment response as compared to Stage III patients (P = 0.099).

On multivariate analysis, only one subgroup of patients who are <60 href="https://www.thieme-connect.com/products/ejournals/html/10.4103/ijmpo.ijmpo_152_16#TB_7" xss=removed>Table 7].

Multivariate analysis of different subgroup of patients in relation to age, stage, and histopathological differentiation with treatment response

Discussion

The value of histopathological differentiation as a prognostic factor for treatment response is controversial. Hardt et al.,[12] in his study observed that there was a lower incidence of complete response to radiation in keratinizing squamous cell cancers (WD) than in large cell nonkeratinizing squamous cell carcinoma, thus concluding that better differentiated forms of squamous cell carcinoma histology have poor treatment response, but no other study has found similar association. In our study, we found no association between histological differentiation and treatment response. Even studies done on head and neck squamous cell carcinoma have shown no relation between differentiation and treatment response.[13]

The relapse pattern in our study showed that distant relapse is more common in PD group as compared with that of WD and MD groups in Stage III as compared to Stage II, showing that less differentiated tumors and advanced stage are more aggressive, similar results were observed in head-and-neck squamous cell carcinoma where PD variety and advanced stage were more prone to nodal metastasis as compared to better differentiated forms.[13] Local recurrence is dependent on stage of the disease (Stage III 14.95% vs. Stage II 7.5%) and not on histopathological differentiation (MD group 11.84% vs. WD 11.75%).

Histopathological differentiation influencing survival in squamous cell carcinoma in either cervix or head and neck is not established even though some studies have found some correlation.[13],[14],[15] Our study too found no correlation between differentiation and survival.

From the facts of radiobiology, it is known that radiosensitivity of squamous cell carcinoma has bell-shaped curve, which ranges from extremely radiosensitive to extremely radioresistant, so the main factor responsible for treatment response seems to be intrinsic radiosensitivity of the tumor cell.[16]In vitro studies have shown intrinsic radiosensitivity of cervix tumors to be independent of disease stage, tumor differentiation, and patient age. However, increased tumor radioresistance for large volume disease has been observed probably due to the presence of hypoxic region in the tumor of large volume disease.[16],[17]

Patients with advanced cancer (Stage III and IVA) have poor treatment response.[12],[18],[19] In our study also, a trend toward a better response in Stage II as compared to Stage III was seen (P = 0.099), but no significant difference was seen probably because most of our Stage II patients had bulky disease (>4 cm).

Age as a prognostic factor for overall treatment outcome of carcinoma cervix is very controversial. Two European studies [7] have shown a better response in younger age whereas others have shown a better response in older patients.[12],[18] Eighty-five percent of our patients were <60>

We observed that histopathological differentiation and age have no association with treatment response but stage and volume of the disease do influence the treatment outcome. Intrinsic radiosensitivity of the tumor is an important factor which determines the treatment outcome. Histopathological differentiation does influence the aggressiveness of the disease with PD tumors being more aggressive than better-differentiated forms.

Conclusion

Advanced stage along with poor histopathological differentiation influences the aggressiveness of the tumor responsible for distant relapse. However, histopathological differentiation has no correlation with local treatment response and overall survival. The other factor influencing the treatment outcome is the intrinsic radiosensitivity of the tumor and volume of the disease, mainly responsible for local control. Intrinsic radiosensitivity of the tumor, which most likely governed by molecular characteristic of the tumor. This work lays the groundwork for identifying the molecular characteristics of differently differentiated tumors as predictive markers of radiation sensitivity and responsiveness.

Conflict of Interest

There are no conflicts of interest.

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Article published online:
17 June 2021

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