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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : -50 مورد

Treatment of locally recurrent rectal adenocarcinoma

Treatment of locally recurrent rectal adenocarcinoma
Authors:
Christopher G Willett, MD
Aparna R Parikh, MD, MS
Brian K Bednarski, MD, MEHP
Section Editor:
Richard M Goldberg, MD
Deputy Editor:
Sonali M Shah, MD
Literature review current through: Apr 2025. | This topic last updated: Feb 28, 2024.

INTRODUCTION — 

For patients with locally advanced rectal cancer without distant metastatic disease, initial management includes some combination of systemic therapy, radiation therapy (RT), and surgical resection (algorithm 1). However, locoregional relapses still occur in 4 to 8 percent of patients who receive appropriate initial treatment for locally advanced rectal cancer [1-3], although distant recurrences still predominate [3-6].

The treatment of locally recurrent rectal cancer is presented here. Other topics related to the management of locally advanced rectal cancer are discussed separately.

●(See "Radical resection of rectal cancer".)

●(See "Neoadjuvant therapy for rectal adenocarcinoma".)

●(See "Adjuvant therapy for resected rectal adenocarcinoma not treated with neoadjuvant therapy".)

THE CHALLENGE OF LOCALLY RECURRENT RECTAL CANCER — 

Management of locally recurrent rectal adenocarcinoma is a significant challenge for a number of reasons:

●Patients with locally recurrent rectal cancer form a very heterogeneous group, ranging from focused anastomotic recurrence to the involvement of adjacent soft tissue organs and the bony structures of the pelvis. Without treatment, these patients have a short life expectancy that is often complicated by relentless pelvic pain, malodorous discharge, and uncontrollable tenesmus, which significantly impairs quality of life [7].

●The clinical nature and prognosis of locally recurrent rectal cancer have changed since the introduction of preoperative radiation therapy (RT):

RT reduces local recurrence at all subsites but is especially effective at preventing anastomotic recurrences [8]. As a result, most recurrences after pelvic RT are not at the anastomotic site, and surgical treatment of nonanastomotic recurrences is more difficult.

Many patients who present with a local recurrence after prior RT have simultaneous distant metastases [9-12]. As an example, in the Dutch total mesorectal excision (TME) trial, 83 of the 129 patients with a local recurrence also had distant metastases (63 percent) [9]. One systematic review concluded that only approximately 40 percent of patients with locally recurrent rectal cancer are candidates for potentially curative treatment [13].

In part related to these issues, long-term outcomes seem to be worse after local recurrence in previously irradiated patients as compared with patients treated initially with surgery alone [8,12,14].

●The choice of therapy must take into consideration prior therapy, the local extent of the recurrence, and whether distant disease is present. For highly selected patients, surgery alone may be associated with long-term survival.

However, for most patients with an isolated local recurrence, combined modality therapy may provide better outcomes, particularly if patients have not been previously irradiated. Patients with distant metastases are usually approached initially with systemic chemotherapy to allow the natural history of the recurrent disease to declare itself. Some of these patients may eventually be determined to have potentially resectable distant (eg, liver, lung) as well as locally recurrent disease. For others who have unresectable distant metastases, palliation of pain, obstruction, or bleeding caused by a locally recurrent primary tumor may usually be achieved through a diverting colostomy or by nonsurgical means, such as with an endoscopically placed, intraluminal, self-expanding metal stent (for tumors not in the mid and distal rectum). (See "Initial systemic therapy for metastatic colorectal cancer" and "Locoregional methods for management of metastatic colorectal cancer", section on 'Management of the primary tumor' and "Enteral stents for the management of malignant colorectal obstruction".)

MODE OF PRESENTATION — 

Approximately one-third of patients may be asymptomatic at the time of recurrence, with the recurrence discovered during a routine postoperative follow-up evaluation [15-18]. (See "Post-treatment surveillance for colorectal cancer".)

Anastomotic recurrence can present with rectal bleeding or alteration of bowel habits. Pain is a more concerning symptom that may be associated with involvement or compression of organs, bone, or nerves.

Local recurrence after an abdominoperineal resection can present with a nonhealing perineal wound, a perineal mass, pelvic pain, or bowel obstruction that results from involvement of small bowel in the pelvic mass.

Up to 74 percent of patients with locally recurrent rectal cancer after combined modality therapy will present with synchronous distant metastatic disease [9-13,19,20].

PRETREATMENT EVALUATION — 

The pretreatment evaluation should focus on assessing fitness for major surgical intervention, tumor staging to ascertain the anatomy and the extent of local and distant disease, and biopsy confirmation of the recurrence. Locally recurrent rectal cancer is challenging to manage, particularly in patients who previously received radiation therapy. Multidisciplinary evaluation to develop the optimal treatment approach is necessary, with input from surgical oncology, medical oncology, and radiation oncology.

Physical examination, laboratory evaluation, and endoscopy — Patients with a suspected or confirmed local recurrence of rectal cancer should undergo a physical examination and digital clinical examination (which may require examination under anesthesia). A full colonoscopy should also be performed to evaluate the anastomotic site and assess the remainder of the large bowel for synchronous lesions.

For women with a suspected anterior recurrence, a vaginal examination must be performed; rarely, cystoscopy is needed in the presence of hematuria or if the scans raise the possibility of bladder invasion. In addition, serum levels of the tumor marker carcinoembryonic antigen (CEA) should be obtained. (See "Clinical presentation, diagnosis, and staging of colorectal cancer", section on 'Clinical staging evaluation' and "Pretreatment locoregional staging evaluation for rectal cancer", section on 'Imaging evaluation'.)

Imaging — All patients with suspected locally recurrent rectal cancer should undergo imaging evaluation to exclude the presence of distant metastatic disease, including a computed tomography (CT) of the chest, abdomen, and pelvis and/or an integrated positron emission tomography (PET)-CT scan. Locally recurrent or metastatic disease should be confirmed by biopsy. Of note, on pretreatment PET-CT imaging, it can be difficult to distinguish between soft tissue with ongoing inflammation that is mildly fludeoxyglucose avid and actual tumor recurrence. Biopsies of this area can be difficult, and a negative result may not be reliable. Sometimes, serial imaging is needed to distinguish between fibrosis and recurrent cancer. (See 'Biopsy' below.)

The preoperative evaluation of any patient with a locally recurrent rectal cancer should also include rectal protocol pelvic magnetic resonance imaging (MRI) [21-23]. High-resolution pelvic MRI is necessary to accurately assess the extent of tumor infiltration and its involvement of adjacent organs and structures. Obtaining high-quality MRI is essential to determine the feasibility of resection with negative margins and to plan for the resection of potentially involved structures. These images, combined with an understanding of the anatomical associations within the pelvis, are critical to planning a surgical approach with the goal of negative resection margins. MRI is preferred over CT imaging, which tends to underestimate the extent of disease, and endorectal ultrasound, which is less helpful for staging a local recurrence after prior surgical resection.

Biopsy — Histologic confirmation of the recurrence is an important step before proceeding with extensive radical surgery, especially if induction chemoradiation is planned. This may be accomplished by colonoscopy for an intraluminal recurrence. When the tumor is not accessible by endoscopy, CT-guided biopsy can often be performed.

When a tissue diagnosis cannot be obtained (eg, as a result of the location of the recurrence or if there is a significant degree of surrounding fibrosis) and there is convincing radiologic evidence of recurrence (eg, highly suggestive PET scan or serial radiologic examinations that demonstrate progressive enlargement of a suspected recurrent mass), it is reasonable to pursue multimodality treatment [24].

Classification of recurrence pattern — Preoperative imaging studies and operative findings are used to categorize the recurrence. There is no universal consensus on the best way to classify locally recurrent rectal cancer for the purpose of prognostication and treatment selection. Several have been proposed:

●A system proposed by the Mayo Clinic classifies patients into groups based on the presence of pain (S0 = asymptomatic; S1 = symptomatic without pain; S2 = symptomatic with pain) and the degree of fixation to anatomical structures located at the anterior, sacral, left, and right sides of the pelvis (F0 = not fixed to any site; F1 = fixed to one site; F2 = fixed at two sites; F3 = fixed at three sites) [25]. While the degree of fixation and pain did not appear to adversely affect survival in their initial report, a subsequent series with more patients indicated significantly reduced survival with symptomatic pain and more than one point of fixation [16].

●A different classification system proposed by the Memorial Sloan Kettering Cancer Center (MSKCC) was based upon the anatomical location of the recurrence within the pelvis and the structures that were involved [26]. Recurrences were defined as one of the following:

•Axial – Anastomotic recurrence after low anterior resection, perineal recurrence after abdominoperineal resection, or local recurrence after transanal excision

•Anterior – Involving urologic or gynecologic organs

•Posterior – Involving the sacrum or coccyx

•Lateral – Involving the pelvic sidewall structures

Using this system, tumors with a lateral component had a significantly reduced likelihood of a microscopically complete (R0) resection.

●Another classification of patterns of invasion was proposed by the Leeds group in 2005 [27]:

•Central – Tumor confined to pelvic organs or connective tissue without contact or invasion into bone

•Sacral – Tumor present in the presacral space and abuts into or invades into the sacrum

•Sidewall – Tumor involving the structures on the lateral pelvic sidewall, including the greater sciatic foramen, and the sciatic nerve through to the piriformis and the gluteal region

•Composite – Sacral and sidewall recurrence combined

This group did not address the prognostic or therapeutic implications of the classification system; however, they did provide an algorithmic approach to surgical management based upon the location of the recurrence.

MANAGEMENT

Surgical resection — Complete radical resection is a prerequisite for cure; outcomes are superior if microscopically complete (R0) resection can be achieved, even if this requires an extensive operative procedure (eg, pelvic exenteration) [28-32]. In these settings, the benefits of surgery (potential for cure, improved symptoms, quality of life) must be weighed against the postoperative morbidity, possibility of multiple permanent stomas, chronic pain, and even the limited survival that result from aggressive surgery.

Complete surgical removal offers the only hope for long-term survival in locally recurrent rectal cancer. External beam radiation therapy (RT) and/or chemotherapy alone may successfully palliate symptoms and prolong median survival to 12 to 15 months (compared with a median survival of three to eight months for untreated local recurrence), but five-year survival rates are <5 percent [17,33-36].

At some institutions, surgical resection alone is pursued for a small subset of patients with an isolated, small, central recurrence at the anastomotic site given some reports of long-term survival if the recurrence can be completely resected with negative margins [15,37-44]. However, others note that oncologic outcomes are poor, even in highly selected patients who undergo surgery for an anastomotic recurrence after transanal excision of an early stage rectal cancer [45,46]. In our view, surgery alone should not be used in the management of a local recurrence if RT has not been previously used. (See 'Patients with no prior radiation therapy' below.)

Even if it has been given within the past year, intraoperative radiation therapy (IORT) may still be an option [47]. (See 'Role of intraoperative radiation therapy' below.)

Aggressive attempts to obtain microscopically negative margins are warranted because a negative-margin resection is the single most important predictor of cancer-specific survival in patients undergoing surgery for recurrent rectal cancer [27,48-53].

For more extensive recurrences, a more extensive surgical procedure (eg, posterior or total pelvic exenteration for an anteriorly located recurrence, abdominosacral resection or partial sacrectomy for a posteriorly located recurrence) may be required. In these settings, the benefits of surgery (potential for cure, improved symptoms, quality of life) must be weighed against the surgical morbidity, possibility of multiple permanent stomas, chronic pain, and even limited survival that result from aggressive surgery. (See "Surgical treatment of rectal cancer", section on 'Multivisceral resection'.)

Resectability in recurrent rectal cancer is defined as the ability to complete a surgical resection with an R0 margin and acceptable postoperative morbidity and mortality. Tumor location and degree of local invasion are the most important factors in determining resectability. Based on evolving data to support radical surgery, specific contraindications to radical resection of recurrent rectal cancer include:

●Extension of tumor through the greater sciatic notch

●Unresectable extrapelvic disease

●Circumferential involvement of the pelvic wall

Relative contraindications before proceeding with radical surgical resection include [24,26]:

●Sciatic nerve root involvement at or above the level of S1-2

●Proximal (S1) sacral invasion extending to the sacral promontory

●Involvement of the paraaortic lymph nodes

●Tumor encasement of the external iliac vessels

In general, these factors preclude a potentially curative surgical procedure. However, there are reports in which extensive sacropelvic resections as well as hemipelvectomies have been performed successfully [37,54-57]. In general, these are very highly selected patients at institutions experienced in these types of procedures, and perioperative morbidity rates are high.

●At the University of Sydney, 49 patients underwent extended resections (defined as higher than the S3 spinal level) for locally recurrent disease. These procedures included 37 total pelvic exenterations [55]. Sixteen patients also had other bony structures resected aside from the sacrum. There were 21 high sacral resections, defined as resection of the sacrum proximal to S3. R0 resection margins were achieved in 74 percent of cases. There were no postoperative mortalities. However, there were 39 percent major morbidity and 78 percent minor morbidity in 40 of the 49 patients (82 percent overall morbidity). Eight of 10 patients resected at the S1 spinal level experienced major morbidity. The estimated five-year disease-free survival was 43 percent in those resected with R0 margins. There was a 45 percent relapse rate. The median overall survival for a patient undergoing R0 resection was 59 months, while it was 28 months for those undergoing R1 (microscopically positive) or R2 (gross residual disease) resection. In this series, six patients developed sensory loss, and seven patients experienced motor deficit postoperatively.

Distant metastases (typically to the liver or lung) may or may not be a relative contraindication to radical surgery depending on the location and potential for curative resection. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy" and "Surgical resection of pulmonary metastases: Outcomes by histology".)

Preoperative imaging is one of the most important tools the surgeon has to select patients for these procedures. It is essential to obtain high-quality pelvic MRI to better evaluate and plan for surgical resection. (See 'Pretreatment evaluation' above.)

Although radical pelvic resection has traditionally been associated with the need for permanent fecal and urinary diversion, continence preservation may be feasible if an oncologically sound resection of the recurrent tumor can be carried out without impairing the integrity of the pelvic floor muscles [58,59]. Ideally, the management of these patients should be by an experienced multidisciplinary surgical team, which may include colorectal surgeons (or surgical oncologists), plastic and reconstructive surgeons, urologists, and neurosurgeons, among others. (See "Surgical treatment of rectal cancer", section on 'Multivisceral resection'.)

Combined modality therapy — For most cases of locally recurrent rectal cancer, we suggest combined modality therapy rather than surgery alone. The specific approach depends on whether the patient received prior RT or not.

Randomized clinical trials are needed to assess combined modality therapy, either in patients who have or have not received prior RT. Most retrospective series of patients treated for locally recurrent rectal cancer include a mix of patients with and without prior RT. In general, most reports show better outcomes, including higher resectability rates, in patients treated with a combined modality approach as compared with surgery alone, regardless of the use of prior RT [15,31,47,49,52,60-63].

The largest series was a pooled analysis of 565 patients treated for locally recurrent rectal cancer at one of two major treatment centers (one Dutch, one American) [31]. Overall, 251 (44 percent) had a radical (R0) resection, and complete resection rates were higher among those who received preoperative treatment (43 and 50 percent for chemoradiation and full-course RT, respectively, compared with 26 percent for those without any preoperative treatment). Patients who were reirradiated had a similar outcome compared with patients who were RT-naïve and could undergo full-course RT, except that they had a higher local recurrence rate. In multivariate analysis, R0 resection and preoperative therapy had an impact on both local recurrence and overall survival.

Patients with no prior radiation therapy — For patients with an isolated local recurrence and no prior RT, we offer a similar approach to preoperative (ie, neoadjuvant) therapy as that used for patients with primary locally advanced rectal adenocarcinoma, with some exceptions. Based on the stage and extent of the local recurrence, options for preoperative therapy include total neoadjuvant therapy (TNT; chemotherapy followed by chemoradiation, or vice versa) and neoadjuvant chemoradiation (with adjuvant chemotherapy after completion of surgery). However, we do not offer neoadjuvant chemotherapy followed by response-guided RT, as this approach (which omits RT in select patients with a clinical response to neoadjuvant chemotherapy) has not been evaluated in patients with recurrent rectal cancer. Further details of the approach to neoadjuvant therapy for rectal adenocarcinoma are discussed separately. (See "Neoadjuvant therapy for rectal adenocarcinoma".)

For patients with bulky recurrent tumors or extensive nodal disease, we offer TNT using an oxaliplatin-based chemotherapy regimen for up to four months [64,65]. Chemotherapy is followed by long-course chemoradiation and then resection. Alternatively, long-course chemoradiation can be administered first, followed by chemotherapy and then resection. For patients with good performance status who are medically fit to tolerate aggressive systemic therapy, we offer preoperative fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) (table 1) to maximize the objective response rate to chemotherapy and the chances of an R0 resection. FOLFOX (fluorouracil, leucovorin, plus oxaliplatin) (table 2) or CAPOX (capecitabine plus oxaliplatin) (table 3) are appropriate alternatives for less medically fit patients at higher risk of treatment-related toxicity. Further details on the approach to TNT are discussed separately. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Total neoadjuvant therapy for locally advanced tumors'.)

Outcomes — The efficacy of concurrent preoperative chemoradiation for locally recurrent rectal cancer in previously unirradiated patients is supported by data from retrospective series [16,18,27,52,66-70] and a single randomized trial of preoperative chemoradiation versus RT alone that included patients with locally recurrent disease [71]. There are no randomized trials of resection alone versus combined modality therapy.

In several retrospective reports, rates of R0 resection in patients undergoing multimodality treatment range from 32 to 82 percent, five-year overall survival rates are 20 to 40 percent (37 to 60 percent among those undergoing R0 resection), perioperative morbidity and mortality rates are 24 to 44 and 0.6 to 9 percent, respectively, and rates of distant recurrence or a second local recurrence are 50 and 38 to 50 percent, respectively [16-18,21,27,66,70].

In the randomized trial, 207 patients with unresectable primary (n = 182) or locally recurrent (n = 25) rectal cancer were randomly assigned to RT (50 Gy) with or without concomitant chemotherapy with bolus fluorouracil [71]. Additional chemotherapy (leucovorin-modulated fluorouracil) was given for 16 weeks after surgery as adjuvant chemotherapy. None of the patients with locally recurrent tumors had been previously irradiated.

In the entire population, compared with preoperative RT alone, preoperative chemoradiation was associated with a significantly higher R0 resection rate (84 versus 68 percent) and pathologic complete response rate (16 versus 7 percent), as well as better five-year rates of local control (82 versus 67 percent), failure-free survival (63 versus 44 percent), and cancer-specific survival (72 versus 55 percent). Results were not stratified according to primary versus recurrent cancer. However, as a group, patients treated for locally recurrent cancer (n = 25) had a worse outcome than did those with primary disease (five-year failure-free and overall survival 30 and 37 percent, respectively). Furthermore, these patients were more likely to be categorically unresectable following preoperative therapy.

Treatment intensification increases toxicity and may not improve outcomes. This was shown in a retrospective report of 102 patients with locally recurrent rectal cancer after surgery alone who were treated with preoperative long-course RT (50.4 Gy) concurrent with FOLFOX given every two weeks for 12 weeks [32]. Ninety-six completed chemoradiation, of whom 75 went on to surgery (low anterior resection in 33, abdominal perineal resection in 23, Hartmann procedure in six, and pelvic exenteration in 13). There were 52 R0 resections, and the remainder had microscopic residual disease (13) or gross disease left behind (10). There were two perioperative deaths (both from sepsis) and 20 surgical complications (20 percent), which included four anastomotic leakages, three pelvic abscesses, eight wound infections, three intestinal obstructions, and two voiding dysfunctions. At a median follow-up of 46 months, the five-year overall and disease-free survival rates were 45 and 14 percent, respectively.

Prognostic factors after combined modality therapy were addressed in a series of 94 patients who received RT for previously unirradiated locally recurrent rectal cancer; 63 also received chemotherapy, and 46 had resection [67]. At a median follow-up of 19 months, tumor recurred locally in 49 (52 percent) and with distant metastases in 57 (61 percent). For the entire cohort, survival rates at one, two, and three years were 74, 56, and 36 percent, respectively. In multivariate analysis, factors that were associated with a significantly greater likelihood of survival were better performance status, lower American Joint Committee on Cancer (AJCC) stage at recurrence, and higher hemoglobin levels during RT.

Role of intraoperative radiation therapy — At many centers in the United States, Europe, and Asia, IORT has been used in conjunction with preoperative irradiation (with and without fluorouracil) and surgical resection when there is strong suspicion for gross residual cancer, positive resection margins, or the presence of tumor adherence to adjacent structures (eg, the pelvic sidewall or sacrum) [31,47,72-78]. IORT is usually not given if at the time of surgery, there is no tumor adherence and adequate soft tissue radial margins are present (>1 cm).

Although there are no randomized trials in which high-risk patients were randomized to receive or not receive IORT, favorable results are reported in series that utilize combined modality therapy that includes IORT administered at the time of surgical resection for locally recurrent disease; in most cases, IORT was preceded by external beam RT, usually with a concurrent fluoropyrimidine [19,31,47,78-83]. The largest series was a pooled analysis of 565 patients treated for locally recurrent rectal cancer at one of two major treatment centers (one Dutch, one American); all but 12 received IORT [31]. Overall, 251 (44 percent) had a radical (R0) resection, and the main factors related to the radicality of resection were preoperative treatment and a longer waiting time from the end of preoperative therapy to surgical resection with IORT. Radical resection was the most important factor influencing all oncologic outcomes. Overall survival rates at three and five years by extent of resection were R0 66 and 48 percent, R1 47 and 25 percent, and R2 37 and 17 percent, respectively.

An important point is that the use of IORT cannot compensate for incomplete resection in such patients [52,81,84]. This was illustrated in a series of 41 patients with locally recurrent rectal or rectosigmoid cancer who were treated with preoperative external beam RT, resection, and IORT [84]. At five years, the local control and survival rates for patients undergoing complete surgical resection were 47 and 21 percent, respectively, while the corresponding values for those undergoing only subtotal resection were 21 and 7 percent, despite the use of IORT in all patients.

Typical IORT doses are in the range of 10 to 20 Gy. The IORT dose is usually 10 to 12.5 Gy in patients undergoing complete resection with negative margins, 12.5 to 15 Gy in patients undergoing subtotal resection with microscopic residual, and 17.5 to 20 Gy in patients with macroscopic tumor after resection.

When IORT is used, it is critical for the surgeon and radiation oncologist to define all high-risk areas to determine the optimal position for the IORT field. To direct the IORT, cones are used with internal diameters ranging from 4 to 8 cm; cone size is selected to fully cover the high-risk area, generally on the sacrum or pelvic sidewall. The cone must abut the site being treated, which can be difficult if the high-risk area is located in an anatomically confined region such as the pelvis. Most IORT treatments in rectal cancer are given through the abdomen, but a perineal port is occasionally used to treat very low-lying tumor involving the coccyx, distal pelvic side wall, or portions of the prostate and bladder when an exenteration is not performed. IORT can also be delivered using high-dose-rate brachytherapy using a Harrison-Anderson-Mick (HAM) applicator. One advantage of the HAM applicator is its flexibility to treat tumors in complex anatomical positions such as narrow cavities, steeply sloping surfaces, or areas where treatment delivery requires "turning a corner" such as retropubic locations [85].

Patients with previous radiation therapy — For patients previously treated with RT, pelvic reirradiation is feasible in selected patients and may permit surgical salvage and long-term survival. Patients being considered for reirradiation need to be carefully selected, and careful attention to dose and technique is required to minimize the risk of serious late effects. Sophisticated RT techniques, such as intensity-modulated RT or proton beam irradiation, are often required to stay within normal tissue tolerance constraints. The dose of RT for reirradiation in this setting should be limited to 30 to 39 Gy. For patients with recurrent rectal cancer who are potential surgical candidates, a treatment strategy of TNT that combines neoadjuvant reirradiation and oxaliplatin-based chemotherapy regimen is used to optimize the chances of an R0 resection.

Surgery alone may result in long-term disease control in some patients who recur locally after prior combined modality therapy; however, outcomes are generally poor, and long-term cures are uncommon [3,14,48]. As an example, in one report of 50 patients who underwent surgical exploration for locally recurrent rectal cancer after primary combined modality therapy, only 24 could undergo an R0 resection (48 percent) [48]. Despite adjuvant chemotherapy in all patients, only eight (16 percent of the total) remained disease free for periods ranging from 21 to 69 months.

Pelvic reirradiation has generally not been undertaken for fear of prohibitive normal tissue complications. However, it is feasible in selected patients and may permit successful surgical salvage and long-term survival, albeit with higher complication rates than with reirradiation alone [52,86-91]. The following studies represent the range of findings:

●The benefits of reirradiation with or without surgery were assessed in a systematic review and meta-analysis of 17 studies (three prospective uncontrolled trials, the remainder retrospective reports) involving 744 patients [91]. For patients who underwent reirradiation plus surgery, pooled one-, two-, and three-year survival rates were 86, 72, and 52 percent, respectively, while for those undergoing reirradiation alone, the corresponding values were 64, 34, and 24 percent, respectively. The benefits of combined modality treatment came at the cost of more grade 3 or worse acute and late complications (12 versus 26 percent in the nonsurgical and surgically treated patients, respectively). In four studies that compared surgically and nonsurgically treated patients, those who underwent surgery had a sixfold higher risk of late complications (gastrointestinal, genitourinary, skin, and soft tissue).

●The importance of R0 resection was emphasized in a retrospective study from the Netherlands of 147 patients with locally recurrent rectal cancer, most of whom (n = 124) underwent preoperative combined modality treatment followed by extensive surgery and IORT; the remainder had surgery with or without postoperative adjuvant treatment [52]. Fifty-seven (39 percent) had undergone prior pelvic irradiation, and their course of RT was limited to 30.6 Gy; other patients received 50.4 Gy.

Patients who received either full-course irradiation or reirradiation as a component of treatment survived significantly longer and lasted longer without local recurrence or metastases than did those who were not irradiated. However, the single most important factor in predicting survival after radical surgery plus IORT for locally recurrent rectal cancer was a negative margin of resection. In the entire cohort, the actuarial five-year overall and cancer-specific survival rates were 32 and 39 percent, respectively, while among those with a R0 resection, the actuarial five-year overall and cancer-specific survival rates were 48 and 58 percent, respectively.

●Long-term toxicity to normal tissues depends in part upon the size of each treatment fraction as well as the total radiation dose. Decreasing the size of each radiation fraction should permit higher total doses without increasing late morbidity. Hyperfractionation administers multiple daily treatments with smaller-than-conventional fraction sizes given over approximately the same treatment duration.

The benefits for hyperfractionated RT in the setting of potentially curative treatment for previously irradiated recurrent rectal cancer have been shown in multiple retrospective reports and uncontrolled studies [87,88,92-94]. In a representative phase II study of 59 previously irradiated patients with an isolated local recurrence of rectal cancer, treatment consisted of hyperfractionated RT administered as 1.2 Gy fractions twice daily to a total dose of 30 Gy; concomitant chemotherapy (infusional fluorouracil) was administered to all patients [93]. Treatment was well tolerated overall; 51 of the 59 patients completed chemoradiation without treatment interruption, while six had a temporary interruption and only two discontinued treatment permanently. Grade 3 or lower gastrointestinal toxicity developed during treatment in only 5 percent, and there was no grade 4 toxicity. Tumor resection was performed in 30 patients (51 percent) and was R0 in 21 (36 percent). Five-year actuarial survival was 39 percent, and it was 67 percent in R0-resected patients. Late toxicities were infrequent and generally mild, and included skin fibrosis, male impotence, urinary incontinence, small bowel obstruction, and dysuria in 2, 2, 1, 1, and 1 percent of treated patients, respectively.

On the other hand, the systematic review mentioned above did not report any significant differences in acute or late toxicity for patients who were reirradiated using hyperfractionation versus conventional fractionation RT [91].

Benefit of adjuvant/neoadjuvant chemotherapy — There are few data to guide the use of adjuvant chemotherapy after combined modality therapy of a locally recurrent rectal adenocarcinoma if it was not administered in the neoadjuvant (induction therapy) setting, and its role is not established. In the few retrospective reports that include the use of adjuvant chemotherapy as a component of combined modality therapy, none of the reports concludes that administration of adjuvant chemotherapy contributed to more favorable long-term outcomes [12,48,61,83,93]. We would generally only consider adjuvant chemotherapy in a patient who had not received treatment with an oxaliplatin-based chemotherapy regimen (eg, FOLFOX, CAPOX) after initial resection.

At many institutions, including that of the authors, patients with bulky recurrent tumors or extensive nodal disease are offered initial chemotherapy with an oxaliplatin-based chemotherapy regimen (eg, FOLFOX, CAPOX, or FOLFOXIRI, unless there is a contraindication to the use of oxaliplatin) for up to four months in responding patients [64,65]. We would not offer adjuvant chemotherapy to a patient who has received preoperative chemotherapy. (See "Adjuvant therapy for resected rectal adenocarcinoma not treated with neoadjuvant therapy", section on 'Oxaliplatin versus fluoropyrimidines alone' and "Adjuvant therapy after neoadjuvant therapy for rectal cancer", section on 'Choice of postoperative regimen' and "Treatment protocols for small and large bowel cancer".)

PALLIATION OF OBSTRUCTIVE SYMPTOMS DUE TO LOCALLY ADVANCED DISEASE — 

Palliation should be considered in symptomatic patients who are not candidates for potentially curative multimodality therapy. Symptom relief can often be achieved through a diverting colostomy, endoscopic laser ablation, or stent placement (for tumors not in the mid or distal rectum); palliative tumor resection is uncommonly needed. This topic is discussed in detail separately. (See "Locoregional methods for management of metastatic colorectal cancer" and "Enteral stents for the management of malignant colorectal obstruction".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Colorectal cancer".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Colon and rectal cancer (Beyond the Basics)" and "Patient education: Treatment of metastatic colorectal cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●General principles – Management of locally recurrent rectal adenocarcinoma is a significant challenge. The choice of therapy depends upon prior therapy, the local extent of the recurrence, and whether distant disease is present. (See 'The challenge of locally recurrent rectal cancer' above.)

●Clinical presentation – Approximately one-third of patients with a local recurrence are asymptomatic, and the recurrence is discovered during a routine postoperative follow-up evaluation. Many patients with locally recurrent rectal cancer after initial combined modality therapy have synchronous distant metastatic disease. (See 'Mode of presentation' above.)

●Pretreatment evaluation – The pretreatment evaluation should focus on assessing fitness for major surgical intervention, tumor staging to ascertain the anatomy and the extent of local and distant disease, and biopsy confirmation of the recurrence. Patients with a suspected or confirmed local recurrence of rectal cancer should undergo (see 'Pretreatment evaluation' above):

•A physical examination and digital clinical examination. Gynecologic or cystoscopic evaluation may be needed for selected patients.

•Serum levels of carcinoembryonic antigen (CEA).

•A full colonoscopy to evaluate the anastomotic site and assess the remainder of the large bowel for synchronous lesions.

•CT of the chest, abdomen, and pelvis and/or a positron emission tomography (PET)-CT scan.

•High-resolution pelvic MRI is essential to determine extent of local tumor and to assess for resectability.

●Surgical resection – Complete radical resection is a prerequisite for cure. Aggressive surgical attempts to obtain microscopically negative margins are warranted due to the superior outcomes with microscopically complete (R0) resection. This may require an extensive operative procedure (eg, pelvic exenteration). (See 'Surgical resection' above.)

Specific contraindications to radical resection of recurrent rectal cancer include:

•Extension of tumor through the greater sciatic notch

•Unresectable extrapelvic disease

•Circumferential involvement of the pelvic wall

Relative contraindications before proceeding with radical surgical resection include:

•Sciatic nerve root involvement at or above the level of S1-2

•Proximal (S1) sacral invasion extending to the sacral promontory

•Involvement of the paraaortic lymph nodes

•Tumor encasement of the external iliac vessels

Distant metastases (typically to the liver or lung) may or may not be a relative contraindication depending on the location and potential for curative resection. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy" and "Surgical resection of pulmonary metastases: Outcomes by histology".)

●Combined modality therapy – For most patients with locally recurrent rectal cancer, especially those who have not received prior pelvic radiation therapy (RT), we suggest combined modality therapy rather than surgery alone (Grade 2C). (See 'Combined modality therapy' above.)

•No prior RT – For patients with an isolated recurrence and no prior RT, we offer a similar approach to preoperative (ie, neoadjuvant) therapy as that used for patients with primary locally advanced rectal adenocarcinoma, with some exceptions. Options for preoperative therapy include total neoadjuvant therapy (TNT) and neoadjuvant chemoradiation (with adjuvant chemotherapy after completion of surgery). However, we do not offer neoadjuvant chemotherapy followed by response-guided RT, as this approach (which omits RT in select patients with a clinical response to neoadjuvant chemotherapy) has not been evaluated in patients with recurrent rectal cancer. Further details are discussed separately. (See 'Patients with no prior radiation therapy' above and "Neoadjuvant therapy for rectal adenocarcinoma".)

•Prior RT – For patients previously treated with RT, pelvic reirradiation is feasible in selected patients and may permit surgical salvage and long-term survival. Patients being considered for reirradiation need to be carefully selected, and careful attention to dose and technique is required to minimize the risk of serious late effects. Sophisticated RT techniques, such as intensity-modulated RT or proton beam irradiation, are required to stay within normal tissue tolerance constraints. The dose of RT for reirradiation in this setting should be limited to 30 to 39 Gy. For those who are potential surgical candidates, a treatment strategy of TNT that combines neoadjuvant reirradiation and an oxaliplatin-based chemotherapy regimen is used to optimize the chances of an R0 resection. (See 'Patients with previous radiation therapy' above.)

●Indications for adjuvant chemotherapy – For patients who do not receive preoperative chemotherapy, the benefit of adjuvant chemotherapy is not established. For most patients, we would consider adjuvant chemotherapy only in a patient who had not received treatment with an oxaliplatin-based chemotherapy regimen (eg, oxaliplatin plus leucovorin and short-term infusional fluorouracil [FOLFOX], oxaliplatin plus capecitabine [CAPOX]) after initial resection. (See 'Benefit of adjuvant/neoadjuvant chemotherapy' above.)

●Patients ineligible for curative therapy – For symptomatic patients who are not candidates for potentially curative multimodality therapy, symptom relief can often be achieved through a diverting colostomy, endoscopic laser ablation, or stent placement (for tumors not in the mid or distal rectum); palliative tumor resection is uncommonly needed. (See 'Palliation of obstructive symptoms due to locally advanced disease' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Miguel A Rodriguez-Bigas, MD, and David P Ryan, MD, who contributed to earlier versions of this topic review.

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Topic 2528 Version 49.0

References

1 : Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial.

2 : Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.

3 : Impact of Recurrence and Salvage Surgery on Survival After Multidisciplinary Treatment of Rectal Cancer.

4 : Long-term oncologic results and complications after preoperative chemoradiotherapy for rectal cancer: a single-institution experience after a median follow-up of 95 months.

5 : Patterns and management of distant failure in locally advanced rectal cancer: a cohort study.

6 : Pulmonary recurrence predominates after combined modality therapy for rectal cancer: an original retrospective study.

7 : The impact of recurrent rectal cancer on quality of life.

8 : Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial.

9 : The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma.

10 : Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate.

11 : Local recurrence of rectal adenocarcinoma after 'curative' surgery with and without preoperative radiotherapy.

12 : Clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision with or without preoperative radiotherapy.

13 : Intentionally curative treatment of locally recurrent rectal cancer: a systematic review.

14 : Does radiotherapy of the primary rectal cancer affect prognosis after pelvic exenteration for recurrent rectal cancer?

15 : Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome.

16 : Curative potential of multimodality therapy for locally recurrent rectal cancer.

17 : A population-based study on the management and outcome in patients with locally recurrent rectal cancer.

18 : Extended radical resection: the choice for locally recurrent rectal cancer.

19 : Intraoperative irradiation after surgery for locally recurrent rectal cancer.

20 : Factors associated with anastomotic recurrence after total mesorectal excision in rectal cancer patients.

21 : Absence of tumor invasion into pelvic structures in locally recurrent rectal cancer: prediction with preoperative MR imaging.

22 : Pre-operative MR assessment of recurrent rectal cancer.

23 : Validation of MRI and Surgical Decision Making to Predict a Complete Resection in Pelvic Exenteration for Recurrent Rectal Cancer.

24 : Management of recurrent rectal cancer.

25 : Curative reoperations for locally recurrent rectal cancer.

26 : Colorectal cancer pelvic recurrences: determinants of resectability.

27 : Surgery for locally recurrent rectal cancer.

28 : Treatment of Locally Recurrent Rectal Carcinoma in Previously (Chemo)Irradiated Patients: A Review.

29 : The Evolution of Pelvic Exenteration Practice at a Single Center: Lessons Learned from over 500 Cases.

30 : Systematic Review of Pelvic Exenteration With En Bloc Sacrectomy for Recurrent Rectal Adenocarcinoma: R0 Resection Predicts Disease-free Survival.

31 : Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres.

32 : Concurrent chemoradiotherapy in the treatment of locally recurrent rectal cancer.

33 : Efficacy of chemoradiotherapy on pain relief in patients with intrapelvic recurrence of rectal cancer.

34 : Surgery and pre-operative irradiation for locally advanced or recurrent rectal cancer in patients over 75 years of age.

35 : Inoperable recurrent rectal cancer: results of a prospective trial with radiation therapy and razoxane.

36 : Management of recurrent rectal cancer: a population based study in greater Amsterdam.

37 : Composite abdominosacral resection for recurrent rectal cancer.

38 : Locally recurrent rectal cancer in Norway.

39 : Analysis of surgical salvage after failure of primary therapy in rectal cancer: results from Intergroup Study 0114.

40 : Abdominosacral resection for locally advanced and recurrent rectal cancer.

41 : Outcome of abdominosacral resection for locally advanced primary and recurrent rectal cancer.

42 : Is curative resection and long-term survival possible for locally re-recurrent colorectal cancer in the pelvis?

43 : Outcome in patients with resectable locally recurrent rectal cancer after total mesorectal excision with and without previous neoadjuvant radiotherapy for the primary rectal tumor.

44 : Surgical treatment of locally recurrent rectal cancer.

45 : Outcomes of salvage surgery for cure in patients with locally recurrent disease after local excision of rectal cancer.

46 : Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence.

47 : Standard fractionation external beam radiotherapy with and without intraoperative radiotherapy for locally recurrent rectal cancer: the role of local therapy in patients with a high competing risk of death from distant disease.

48 : Prognostic and predictive factors after surgical treatment for locally recurrent rectal cancer: a single institute experience.

49 : Prognostic factors after surgery for locally recurrent rectal cancer: an overview.

50 : Clinical algorithms for the surgical management of locally recurrent rectal cancer.

51 : Prognostic factors affecting oncologic outcomes in patients with locally recurrent rectal cancer: impact of patterns of pelvic recurrence on curative resection.

52 : Radical resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer.

53 : Factors affecting outcomes following pelvic exenteration for locally recurrent rectal cancer.

54 : Extended sacropelvic resection for locally recurrent rectal cancer: can it be done safely and with good oncologic outcomes?

55 : Assessing the impact of a sacral resection on morbidity and survival after extended radical surgery for locally recurrent rectal cancer.

56 : Sacral resection with pelvic exenteration for advanced primary and recurrent pelvic cancer: a single-institution experience of 100 sacrectomies.

57 : Abdominosacral resection: long-term outcome in 86 patients with locally advanced or locally recurrent rectal cancer.

58 : Preservation of bowel and urinary continence in the management of locally recurrent rectal cancer.

59 : Pelvic exenteration for advanced colorectal cancer with reconstruction of urinary and sphincter functions.

60 : Surgery for locally recurrent rectal cancer in the era of total mesorectal excision: is there still a chance for cure?

61 : The Outcomes and Patterns of Treatment Failure After Surgery for Locally Recurrent Rectal Cancer.

62 : Curative surgery for local pelvic recurrence of rectal cancer.

63 : Impact of multimodal therapy in locally recurrent rectal cancer.

64 : Improved Outcomes for Responders After Treatment with Induction Chemotherapy and Chemo(re)irradiation for Locally Recurrent Rectal Cancer.

65 : Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer.

66 : Intraoperative electron and external beam irradiation with or without 5-fluorouracil and maximum surgical resection for previously unirradiated, locally recurrent colorectal cancer.

67 : Prognostic factors affecting locally recurrent rectal cancer and clinical significance of hemoglobin.

68 : Extensive surgery after high-dose preoperative chemoradiotherapy for locally advanced recurrent rectal cancer.

69 : Is en-bloc resection of locally recurrent rectal carcinoma involving the urinary tract indicated?

70 : Preoperative irradiation and surgery for recurrent rectal cancer. Will intraoperative radiotherapy (IORT) be of additional benefit? A prospective study.

71 : Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer.

72 : Outcomes of clinical T4M0 extra-peritoneal rectal cancer treated with preoperative radiochemotherapy and surgery: a prospective evaluation of a single institutional experience.

73 : The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer.

74 : Unresectable colorectal cancer can be cured with multimodality therapy.

75 : Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy.

76 : Patterns of failure and local control after intraoperative electron boost radiotherapy to the presacral space in combination with total mesorectal excision in patients with locally advanced rectal cancer.

77 : Patterns of local recurrence in locally advanced rectal cancer after intra-operative radiotherapy containing multimodality treatment.

78 : Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience.

79 : High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer.

80 : Intraoperative electron beam radiation therapy for locally recurrent rectal carcinoma.

81 : Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer.

82 : Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer.

83 : Intraoperative Electron Radiation Therapy (IOERT) in the management of locally recurrent rectal cancer.

84 : Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

85 : Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

86 : Long-term results of reirradiation for patients with recurrent rectal carcinoma.

87 : Reirradiation of locally recurrent rectal cancer: a systematic review.

88 : Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation.

89 : Feasibility of reirradiation in the treatment of locally recurrent rectal cancer.

90 : The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

91 : Practical effectiveness of re-irradiation with or without surgery for locoregional recurrence of rectal cancer: A meta-analysis and systematic review.

92 : Accelerated hyperfractionation field-involved re-irradiation combined with concurrent capecitabine chemotherapy for locally recurrent and irresectable rectal cancer.

93 : Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study.

94 : Hyperfractionated accelerated reirradiation for rectal cancer: An analysis of outcomes and toxicity.