Comprehensive Treatment and Prognostic Factors in Patients with Carcinoma of the Cervical Stump

Discussion

The diagnostic rules and therapeutic principles pertaining to CCS patients are usually the same as those for CACX patients, and pathologic examination of cervical tissue is the golden standard for the diagnosis of CCS^[4]. After STH, however, the cervical stump may develop a tight adherence to the urinary bladder, rectum, and even to peripheral tissues, thus increasing the difficulty of a second surgery. Therefore, the treatment method should vary from person to person, and the changes in pelvic anatomy, gross tumor volume and clinical stage, should be considered when a second surgical procedure is performed in order to, in advance, avoid, or, in time, treat the complications. Frequently seen prognostic correlation factors of CACX include pelvic lymphatic metastasis, infiltration into surrounding tissue, depth of infiltration into the cervical mesenchyma, vascular tumor embolus, tumor size, clinical stage, histologic grade, and radiochemotherapy^[5-7]. The results of our study revealed that pelvic lymphatic metastasis and vascular tumor embolus are 2 independent prognostic factors of survival. In general, the spread of CCS and the route of metastasis are similar to those of CACX. Nevertheless, nodal metastasis of occult cancer is more common and rather extensive. Surgery can result in derangement of and sabotage to parametrial tissue including that of the lymphatic system. The extensive bypass circuit of the lymphatic network which develops after surgery may increase the possibility of lymphatic metastasis. Although in this study no statistical differences were found in the comparison of disease among patients with different clinical stages, it was obvious that the survival rate of patients decreased with an increase in stage. Following conventional therapy, distant metastasis was slightly more prevalent than regional relapse, and the incidence of the complications was high. Since the small sample size and the varied clinical stages of patients in our study group may affect the prognostic factors, our suggestion for patients with high pathologic risk factors after STH is that extracorporeal and intra-vaginal canal radiotherapy or radiochemotherapy of the total pelvic cavity should be conducted in order to reduce pelvic recurrence or distant metastasis.

Radiotherapy refers to every stage of CCS. However, the curative effect is especially favorable for the middle-late stage patients undergoing radiation therapy with adjuvant chemotherapy. Therefore, a rational individualized therapeutic regimen should be adopted based on factors including clinical stage, extent of the regional involvement, length of the cervical stump canal, age, patient’s condition and underlying medical history. For the past few years, extracorporeal irradiation was the primary radiotherapy, and intracavitary irradiation was considered adjuvant. Since the uterine body is removed during STH, the placement of the radioactive source is restricted and is inserted into the cervical canal, which results in a changed radiation dose to the central axis of pelvic cavity and to the pelvic wall. Difficult placement of the intracavitary radioactive source in the cervical canal also brings about an unsatisfactory dose distribution, resulting in failure of the optimum dose. At the same time, an intracavitary below standard dosage requires a compensatory increased dosage of extracorporeal or vaginal irradiation, resulting in increased radiotherapy-induced complications, especially so in the advanced CCS patients. Postoperative adhesions, pelvic fibrosis and blood circulation disturbances decrease the tolerable dose of the radiation in patients, which also increases the probability of the complications^[8]. In recent years, conformal and intensity modulated radiation therapy have been adopted, which can raise the target site dose of the tumor, and reduce the exposure dose in the major peripheral organs, and therefore, reduce the complications induced by radiotherapy^[9].

Neoadjuvant chemotherapy, synchronized radiochemotherapy and radiosensitization have been frequently used in CCS cases, and chemotherapy via pelvic arterial cannula has been done in advanced stage CCS cases to improve the concentration of topical remedies and the curative effect. Neoadjuvant chemotherapy is applicable to patients with locally advanced disease and a larger tumor volume, with the expectation of increasing the success rate of surgery, reducing tumor dissemination and eliminating the subclinical foci of infection, such as the non-palpable masses. However, there are disadvantages because neoadjuvant chemotherapy is time consuming and costly. Synchronized radiochemotherapy can reduce the size of tumors and eliminate foci of micrometastasis. Additionally, it has a synergistic effect with radiotherapy in reducing the number of tumor cells, in accelerating cell growth and in the development of cross tolerance. Frequently used chemotherapeutic regimens include 5-FU + DDP. Monofactorial analysis in our group indicated that synchronized radiochemotherapy had statistical significance for the prognosis and treatment of CCS. The result of SCC-Ag detection before and after treatment can favorably reflect the status of tumor load and can be regarded as part of the routine examination in the follow-up after STH and in the excision of CCS.

Previously, it was reported that the utilization of STH plus partial resection of the central axis of the cervical canal could result in scarring of regional fibrous tissue, causing the cervical stump to be restricted, long term, blood supplied by small vessels. This results in the loss of a substantive nutrient source to new cells and in a reduction in the incidence of atypical hyperplasia as well^[10]. Concerning the patients who require preservation of the uterine cervix or those with an expected difficulty during the trachelectomy, routine cervical and cervical canal liquid-based cytologic film preparations should be performed, and procedures such as vaginoscope-guided cervical biopsy and fractional curettage should be done, if necessary. For patients with suspicious symptoms or physical signs, though they may not be visible, a conclusive diagnosis can be made by a 3-step diagnostic procedure, i.e., the cytological examination of the cervix, vaginoscopy including colposcope-guided biopsy plus cervical canal curettage, and pathologic examination. Attention should likewise be paid to the clinical indications of STH, including patient from 35 to 40 years of age or even younger, difficulty in performing total hysterectomy, severe complications and poor tolerance to surgery requiring that the duration of surgery be minimized^[11]. Postoperative regular examination of the cervix, close follow-up and observation are very important in preventing the occurrence of CCS.

The incidence rate of CCS is low, but the disease is difficult to cure. The incidence of the complications is high, and distant metastases are commonly seen. Thus, individualized treatment is essential. At present, combined therapy, such as the combination of surgery with chemotherapy and radiotherapy, has improved the cure rate. However, prevention is still the key to precluding the occurrence and reducing the incidence of CCS. It is necessary to strictly regard the indications for STH and to reinforce close postoperative follow-up.