In general, local recurrence is the reflection of an aggressive biological behaviour of the primary tumour as it is accompanied by synchronous distant disease in a high percentage of patients. In the Dutch TME trial,58
83 of 129 patients (63%) with local recurrence also had distant metastases. The Swedish Rectal Cancer Trial and Stockholm I trial reported distant disease in 66 of 143 patients (46%) and 86 of 156 patients (55%) with local recurrence, respectively.59,60
Our systematic review suggests that 40% of unselected consecutive patients with locally recurrent rectal cancer are candidates for intentionally curative treatment. Curative treatment of both local and distant recurrence is achievable in only a small subgroup of patients (). Probably such treatment should only be considered in patients with indolent tumour behaviour based on a long disease-free interval (at least 2 yr) from primary treatment.
Overall, half of the patients were classified as having S2 clinical presentation (symptomatic with pain). Although these were selected patients who were candidates for intentionally curative treatment, this finding is concordant with an unselected cohort of 156 patients with locally recurrent rectal cancer from the Stockholm Rectal Cancer Study: the rates of S0, S1 and S2 clinical presentation were 13%, 33% and 54%, respectively.60
Intractable pain associated with a pelvic recurrence is an awful clinical condition. While distant disease is the determining factor for prognosis in most of these patients, local recurrence will generally affect quality of life.61,62
Complete or partial initial relief of pain after radiotherapy alone or after multimodality treatment, including surgery, is reported in up to 83% of patients, although the rate of long-term pain-free survival is about 30%.27,41,63
The 2 most important predictors of radical resection of local recurrence are previous anterior resection instead of APR and the absence of pain at the time of recurrence.43,64,65
Intraluminal recurrences, especially after initial local excision, are separated from the bony pelvis and sacral nerves by remaining soft tissue, thereby not resulting in pain and enabling resection with adequate margins in almost all patients.26,35,39
Given the worse outcome for local recurrence after prior APR, optimal primary treatment of distal cancers is of utmost importance. The pelvis becomes narrower at the level of the levator ani. When following this natural curve, the surgeon will end up with a so-called coning resection, thereby increasing the risk of tumour-positive margins. The extralevatoric APR with en bloc removal of the levator muscle in combination with downstaging by neoadjuvant therapy will improve local control in distal rectal cancers.66,67
We found a wide variety in treatment protocols with regard to perioperative radiotherapy for locally recurrent rectal cancer reported in the studies we reviewed ( and ). Some institutes did not include EBRT or IORT in their protocols, while the indication for radiotherapy ranged from highly selective to routine use at other centres. In addition, EBRT had been applied either in the preoperative or in the postoperative setting. Chemotherapy was not always added as radiosensitizer, especially in series published before 2005. The indication for EBRT did not depend only on prior EBRT; comparing data on EBRT from and revealed that some patients received no irradiation during the entire treatment, neither for the primary tumour, nor for the local recurrence. On the other hand, there is a tendency toward reirradiation in patients with locally recurrent rectal cancer after prior pelvic radiotherapy.
There is no concluding evidence to determine the most optimal treatment strategy for locally recurrent rectal cancer. This is also related to the heterogeneity of the disease, as shown in the present review, based on type of primary surgery, previous radiotherapy, extent of recurrent disease (i.e., fixation grade, extension to pelvic sidewall) and the presence of symptoms or distant metastases. The available data do not enable pooling of data from several subgroups to compare different treatment approaches among different disease entities. However, there is increasing consensus that EBRT should be given preoperatively with concurrent chemotherapy, as demonstrated by papers published since 2006 (). This recommendation is based on the need for optimal preoperative downsizing and downstaging to maximize the chance of an R0 resection, which is the most important predictor for survival after treatment for locally recurrent rectal cancer.68,69
The calculated overall R0 resection rate of 56% leads us to conclude that there is room for improvement. The use of IORT is still controversial, and data from randomized controlled trials are lacking.
There is a need for more complete and uniform reporting on outcome parameters (). Better comparison of data can be achieved by determining outcomes for similar groups of patients (e.g., those who undergo R0 or R0/R1 resection) using standardized parameters, such as 3- and 5-year local control and overall survival. Missing follow-up data and inappropriate length of follow-up in most of the remaining studies reflect the low quality of available data on the treatment of locally recurrent rectal cancer.
The use of EBRT for primary rectal cancer has increased during the past decades. Without previous radio-therapy, patients with locally recurrent rectal cancer can be optimally treated by full-dose (chemo)radiotherapy. In the Dutch TME trial, radiotherapy at a dose of 45 Gy or higher was applied in 42% of patients for local recurrence after TME alone, whereas the rate was only 4% for the preoperative radiotherapy group.69
A radiotherapy dose less than 45 Gy was associated with shorter survival after local recurrence in both univariable and multivariable analysis. Long-term follow-up of the Swedish and Dutch rectal cancer trials showed that time from local recurrence to death was significantly shorter in the irradiation group than in patients who underwent surgery alone.59,69
Thus, radiotherapy does not affect systemic dissemination and, therefore, local recurrences after radiotherapy are more often concomitant with distant disease, leading to a worse prognosis from time of local recurrence. From these data, it can be concluded that radiotherapy for primary resectable rectal cancer mostly prevents potentially curable local recurrence. More selective application of neoadjuvant therapy for primary resectable rectal cancer can minimize early and late adverse effects, and broadens therapeutic options if local recurrence develops.