Neoadjuvant radiotherapy in stage I cancer of the lower rectum

Introduction: The mortality rate in low rectal cancer is related to pelvic and distant recurrence. For stage I tumors, local excision has being used increasingly, but recent studies show the need for caution with the use of this technique, as they do not consider the possibility of a positive node in stage I rectal tumors. Therefore, preoperative radiotherapy should be considered for early tumors, as an attempt to prevent recurrence. Objective: Show the effectiveness of neoadjuvant radiotherapy in stage I cancer of the lower rectum of a cohort population. Material and method: A cohort study in a prospective database was made with a total of 538 patients, of which were considered 75 patients with stage I lower rectal cancer. Preoperative radiotherapy was performed and patients were followed up for a minimum period of five


Irradiation a b s t r a c t
Introduction: The mortality rate in low rectal cancer is related to pelvic and distant recurrence. For stage I tumors, local excision has being used increasingly, but recent studies show the need for caution with the use of this technique, as they do not consider the possibility of a positive node in stage I rectal tumors. Therefore, preoperative radiotherapy should be considered for early tumors, as an attempt to prevent recurrence.
Objective: Show the effectiveness of neoadjuvant radiotherapy in stage I cancer of the lower rectum of a cohort population.
Material and method: A cohort study in a prospective database was made with a total of 538 patients, of which were considered 75 patients with stage I lower rectal cancer. Preoperative radiotherapy was performed and patients were followed up for a minimum period of five years.
Results: Stage I/TI group had 27 patients. All of them presented complete response to the treatment and did not need to be operated. During the follow up time of five years, this group showed no recurrence rate. The stage I/TII group had 48 patients. During the follow up, 8 patients had to be operated due to suspicious lesion or scar. They were submitted to full total local excision. After evaluating the pathological specimen, none of them proved to be adenocarcinoma.
Conclusion: Preoperative radiation, not only reduced the local recurrence and mortality rate in lower rectal cancer, but also reduced the need for surgery in patients with stage I cancer.

Introduction
Preoperative radiotherapy in cancer of the lower rectum has been used since 1975. 1 However, during the last decade substantial progress has been made in treatment modalities. The surgical management currently includes a broad spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques; new and improved radiation techniques emerged (conformal radiotherapy, intraoperative radiotherapy) with or without combinations of chemotherapies. [2][3][4][5] The mortality rate is related to pelvic and distant recurrence. 6 Therefore, adequate surgical technique is mandatory in the treatment of the rectal cancer. 6,7 Also critical is the role of prognostic factors such as the pathologic T (tumor) and N (nodal) classification, circumferential resection margin, and response to preoperative therapy. 3 Nodes can be positive even in early tumors. 8 For stage I rectal cancer, local excision has being used increasingly, but recent studies show the need for caution with the use of this technique, as they do not consider the possibility of a positive node in stage I rectal tumors. 3,7,8 Nowadays, appropriate staging plays an increasingly important role, because many treatment decisions must be based on preoperative staging. 2,3 Current guidelines advocate for neoadjuvant treatment for stage II and III tumors, once it has been proved that preoperative radiation reduces local recurrence risk and improve long-term survival. [9][10][11][12] However, knowing that pre-operative radiotherapy is able to decrease, significantly, the number of undifferentiated cells; diminish the grade of tumor invasion in the rectal wall; reduce, statistically, the incidence of local recurrence and alter longterm survival rate leads to believe that neoadjuvant therapy should be used in early tumors as well, preventing a recurrence rate many times reported in stage I patients. 1 Objectives Show the effectiveness of neoadjuvant radiotherapy in stage I cancer of the lower rectum of a cohort population.

Methods
A cohort study in a prospective database was made from 1978 to 2012, with a total of 538 patients with lower rectum cancer, of which were considered 75 patients with stage I cancer. These individuals were submitted to preoperative radiotherapy. They were 27 patients stage I/TI and 48 patients stage I/T2. All of them had lower rectum adenocarcinoma and were followed by a 5-year minimum.
There was no gender, race and age distinction. Preoperative dosage of CEA, gamma GT, colonoscopy and abdominal ultrasound were performed in all the patients to stage the tumor. When available endorectal ultrasound was performed to evaluate size and infiltration of the tumor before and after the irradiation.
Proctoscopy and digital examination were performed at diagnosis and after the end of the irradiation treatment to evaluate tumor extension and wall infiltration.
Preoperative radiotherapy was performed with 200 cGy/daily for 4 consecutive weeks up to a total of 4500 cGy, by means of a linear megavoltage accelerator (25 MeV), in anterior and posterior pelvic fields.
Post-radiation protocol included periodical examination every 3 months for the first two years, with digital examination (or careful perineal palpation) and evaluation of the CEA and every 6 months for the next consecutive three years. Abdominal ultrasound was performed yearly and colonoscopy every other year. When clinical assessment suggested local or general recurrence, a CT scan or MR was accomplished.

Results
The 75 patients with lower rectum cancer were followed for a minimum period of 5 years.
The stage I/TI group had 27 patients, all of them submitted to the same protocol of neoadjuvant therapy. Everyone presented complete response to the treatment and did not need to be operated. During the follow up time of five years, this group showed no recurrence rate.
The stage I/TII group had 48 patients, all of them submitted to the same protocol of neoadjuvant therapy. During the follow up, 8 patients had to be operated due to suspicious lesion or scar. They were submitted to full total local excision. After evaluating the pathological specimen, none of them proved to be adenocarcinoma. It was found dysplasia and adenoma (Fig. 1).
One patient of this group had a distant metastasis, after 5 years that occurred in the lungs (Fig. 2).
The other 40 patients had complete response after neoadjuvant radiotherapy.

Discussion
Treatment of rectal cancer has dramatically evolved during the last three decades shifting toward a tailored approach  based on preoperative staging and response to neoadjuvant therapy. 13 Preoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer and recurrence, especially locally, is responsible for the great majority of deaths in the first two years after surgery. 14 Previous studies showed that there is a significant difference in the five-year survival rates in patients receiving preoperative radiotherapy, who had a corrected survival rate of 80% versus 34.4% of nonirradiated patients. The local recurrence rate was 2.9% in patients that received neoadjuvant therapy versus 23.5% in those who had not. 1 Endorectal ultrasound (ERUS) displays accuracy of 71-91% and 69-97% for T stage, and 62-83% for nodal staging. 15 Results confirmed in 200 patients, that after the irradiation an involution of the tumor size and volume occurred. 1 Comparing to other studies when preoperative radiotherapy was not used the recurrence rate was much higher. [15][16][17][18][19] According to Aguilar, patients undergoing local resection presented recurrence rate of 18% (T1) and 37% (T2) with 54 months of follow-up.
Patients undergoing local excision with transanal endoscopic microsurgery presented recurrence of 13% (T1), 17% (T2) with follow up of 24 months. 18 Bebenek showed 4.4% recurrence rate for T1 and T2 in two year follow up after abdominoperineal resection. 20 On the other hand, Lezoch showed a recurrence rate similar to the one presented in this study, with no recurrence in T1 and 2.85% in T2. The similar results are due to the use preoperative radiotherapy before performing a transanal endoscopic microsurgery. 21,22 Those results shown that receiving neoadjuvant therapy carries less risk of local recurrence than surgical techniques that did not receive pre operative radiotherapy (local excision, transanal endoscopic microsurgery, abdominoperineal resection, low anterior resection) ( Table 1).
A decrease of lymphatic invasion in patients that received preoperative radiotherapy is observed, and also confirmed through endorectal ultrasound, digital examination and endoscopic an involution on the size and volume of the tumor. 23,24 This study did not contemplate the possible complications presented by radiotherapy or alluded to molecular analysis since this was not its goal.

Conclusion
In this cohort, the use of neoadjuvant radiotherapy reduced the risk of local recurrence, the mortality rate, and the needed of surgery in stage 1 cancer of the lower rectum.