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Surgical Management of Recurrent Rectal Cancer

April 25, 2023 - read ≈ 22 min

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Author

Kellie L Mathis, MD, MSc, Professor of Surgery

Mayo Clinic, 200 First Street SW, Rochester, MN, USA 55905

Content

Introduction

Many changes have occurred in the management of rectal cancer in the last several decades. These changes have included transition of radiation and chemotherapy to the neoadjuvant setting, new and improved chemotherapy regimens, and focus on high quality surgery with total mesorectal excision. Together, this change in strategy has resulted in a dramatic decrease in local recurrence rates from 20%[1] down to approximately 10%.[2]

Similarly, changes have been made in the management of locally recurrent disease. Presentations like sacral invasion and involvement of major vasculature that were previously considered contraindications to surgical intervention may now be considered resectable in highly specialized centers.

Locally recurrent rectal cancer is defined as a recurrence (usually pelvic) following surgical resection for a primary rectal cancer in the absence of unresectable distant metastasis.  Most local recurrences occur within the first 2 years of completion of treatment for the primary disease,[3, 4] and 80% of local recurrences occur by 5 years.[5] Without treatment, the prognosis for locally recurrent rectal cancer is dismal with a 5 year survival of approximally 9%.[6]

This chapter will briefly overview the presentation, diagnosis, multidisciplinary management, and outcomes of recurrent rectal cancer.

Symptoms

Following treatment of primary rectal cancer, patients should be surveyed for a total of 5 years.  This includes a regular history and physical, regular carcinoembryonic antigen (CEA) evaluation, frequent endoscopy to evaluate the anastomosis if present and rule out metachronous lesions in the remainder of the colon, and computed tomography (CT) scans of the chest and abdomen to rule out metastatic disease.[7, 8]

Many patients with locally recurrent rectal cancer are asymptomatic and the local recurrence is suspected based on a CEA elevation or is seen on imaging and/or endoscopy that is done as part of the surveillance regimen.[2, 9]

In symptomatic patients, the most common symptoms are change in bowel habits consistent with obstruction, hematochezia, and pelvic pain.

Risk factors for local recurrence

Risk factors for the development of locally recurrent rectal cancer include characteristics of the primary tumor such as distal location, need for abdominal perineal resection, advanced T stage, advanced N stage, poor differentiation, lymphovascular invasion, the presence of lateral pelvic lymph nodes on initial presentation, extramural venous invasion, preoperative obstruction, preoperative perforation, and fistulization.

Surgical factors such as a positive circumferential resection margin are also predictive of recurrence.[5, 10, 11]

Diagnostic Work-Up

Given the high associated morbidity for surgery for local recurrence, it is imperative to select the patients who are most likely to benefit and avoid a highly morbid operation in patients who are unlikely to have an R0 resection. 

The diagnostic workup includes a general physical exam, laboratory studies including a CEA, CT scans of the chest abdomen and pelvis to rule out metastatic disease, a pelvic Magnetic Resonance Imaging (MRI) exam to understand the local invasiveness of the tumor, and a colonoscopy to exclude any neoplasm in the remaining colon.

Any concerns for metastatic disease seen on the CT scans of the chest abdomen and pelvis generally prompt other testing.  Concerning chest lesions are followed by a Positron Emission Tomography (PET) scan and on some occasions a biopsy.  Indeterminate lesions in the liver are worked up with a liver MRI, and liver lesions that remain concerning are biopsied.[12]

For the pelvic disease, a specialized MRI of the pelvis is critical to determining local resectability.  There is difficulty distinguishing postoperative change and radiation change from recurrent tumor.  Generally, fibrosis near a tumor should be considered malignant and surgical planning should involve the intent to remove tissue beyond these areas of fibrosis.[13-18] The radiologic evaluation in the pelvis should include mention of the involvement of pelvic bones, pelvic organs, pelvic nerves, pelvic vessels, the ureters and any additional involved or adjacent structures.[14]

PET scans have been advocated to assist with the distinction between postoperative change and tumor in the pelvis.  Generally, we would expect minimal uptake of fluorodeoxyglucose (FDG) in the setting of fibrosis.  However, mucinous and signet ring tumors are usually of low cellularity and may lead to false negative PET results.  And inflammation in the pelvis may signal a false-positive PET result.[19-21] PET remains a tool, but the limitations should be considered.

Many classification systems have been developed and described.[22, 23]  The Memorial Sloan Kettering Cancer Center classification highlights four regions of recurrence in the pelvis, including anastomotic/central, anterior, lateral, and posterior.[22] Recurrence distribution is fairly balanced with 13-37% occurring centrally or around the anastomosis, 16-30% occurring in the anterior region, 18-25% occurring in the lateral compartments, and 10-41% occurring in the posterior region.[24, 25]

After the workup is complete, the patient should be discussed in a multidisciplinary tumor board with surgeons, radiologists, pathologists, radiation oncologists, and medical oncologists.  This group should be responsible for determining the feasibility of resection and associated treatments.

In general, the patient should have no unresectable distant metastatic disease, the surgeon should feel that an R0 resection is possible (or R1 with planned intraoperative radiation therapy), and the patient should be  physically and psychologically fit to undergo a major operation.[26]

Contraindications to surgery

The absolute contraindications to surgical resection for locally recurrent rectal cancer include a patient with poor performance status, bony involvement above the S1 level of the sacrum, multifocality in the pelvis, and extensive and especially bilateral pelvic sidewall involvement.[13, 14, 26] Additionally, when the surgeon feels that an R2 resection margin is likely, no surgery should be offered since there is no associated survival benefit.

Management

The PelvEx Collaborative is an international group of surgeons who routinely perform pelvic exenteration for locally recurrent rectal cancer, and they have recently issued a statement summarizing their comprehensive recommendations for the management of locally recurrent rectal cancer.[14]

Neoadjuvant treatment

Chemotherapy – Just as we have moved toward a total neoadjuvant therapy approach for primary rectal cancer, there is increasing interest in moving chemotherapy to the preoperative setting for locally recurrent rectal cancer.  This allows better compliance with the completion of chemotherapy, the possibility of downstaging the tumor to allow wider margins, and early systemic exposure for any unseen micrometastatic disease.  There are currently two randomized controlled trials enrolling patients for the management of recurrent rectal cancer.

  • The 1st is the GRECCAR 15 trial[27] where patients are randomized to chemotherapy followed by radiation (or reirradiation) combined with chemotherapy in the neoadjuvant setting versus neoadjuvant chemotherapy only.
  • The 2nd is the PelvExII trial[28] where induction chemotherapy followed by chemoradiotherapy in the neoadjuvant setting will be compared to neoadjuvant chemoradiotherapy only.[14]

Chemoradiotherapy – Neoadjuvant long course chemoradiotherapy is used to downsize and down stage locally recurrent rectal cancers prior to surgical resection.  This regimen has been shown to improve resectability as well as local control and may be associated with an improvement in survival.[29, 30]

When the patient is radiation naive, a full course of neoadjuvant long course chemoradiotherapy with 50.4 Gy over 28 sessions is the standard of care followed by a wait time of 4-8 weeks prior to surgery.[31]

However, most patients with locally recurrent rectal cancer have received neoadjuvant or adjuvant radiotherapy as part of the treatment for the primary tumor.  Many studies have evaluated the safety and efficacy of reirradiation in this setting, and this has become the standard of care.[30, 32]

When a patient has previously received 50 Gy of external beam radiation therapy, our protocol is to administer an additional 3 weeks of neoadjuvant chemoradiotherapy with an additional 30 Gy of external beam radiation.  This is followed by immediate surgery with no delay and intraoperative radiation therapy (IORT) is given for any close or positive margins.  But it should be noted that the benefits of IORT have been disputed and it is a controversial technique outside of a few specialized centers.[33]

Pre-operative Considerations

After the patient is deemed a surgical candidate, it is very important that the patient be counseled about pre-rehabilitation opportunities.  There is generally time during chemotherapy and/or radiation therapy to optimize nutrition, start an exercise program, and manage any psychosocial concerns.

Optimization of nutrition has been associated with improved perioperative outcomes in other cancer sites[34] and this data can likely be extrapolated to recurrent rectal cancer.

Surgery

The goal of any operation is to achieve an R0 resection.  Again, an R0 resection is the single most important prognostic factor associated with long-term survival.  This goal must be balanced with the morbidity associated with surgery as well as the anticipated quality of life related to any longstanding morbidities.

Anterior Compartment – Anterior disease is considered the most favorable as it is generally possible to achieve widely negative margins with an en bloc resection of the genitourinary structures.  Resection of the pubic bone has been described.  Various reconstruction options exist for the urinary tract, as discussed below.

Lateral Compartment – Disease in the lateral compartment is considered the most difficult location for recurrent rectal cancer due to the presence of many critical structures, including the iliac vessels, the obturator and sciatic nerves, the ureters, etc.  And historically, R0 resection has also been difficult to achieve in the lateral compartment.

Newer techniques involve a complete compartment excision dissecting outside the usual plane (lateral to the iliac vessels).  Single center experience with this technique has led to high R0 rates of up to 68% and long-term median survival of 41 months.[35]

Posterior Compartment – Generally, a sacrectomy will be performed when there is direct invasion of the bone by the tumor. The sacrectomy is often performed from the combined abdominal lithotomy position when the bony involvement is all below S3, but when it is involved at S3 or higher, a prone position will be necessary in addition to the abdominal phase.[35] Low sacrectomy (below the level of S3) should be routinely offered and is associated with high R0 rates and low rates of complication.[36]

Reconstruction – Once the specimen has been resected, filling and or reconstruction of the pelvic defect is preferred, usually with a vascularized flap (omentum, rectus muscle).[37]  When the dead space in the pelvis is not obliterated, there is risk of the development of empty pelvis syndrome.  This has been associated with the accumulation of fluid in the pelvis as well as small-bowel migration into the pelvis which can lead to bowel obstruction in both the short and long-term settings.[38]

When there is a perineal wound, the perineal skin can often be closed primarily, but in the case of an extra levator resection, a vascularized flap with an attached skin paddle may be necessary to bridge the gap created.  Bilateral gluteal advancement with myocutaneous or fasciocutaneous flaps have also been well described in this setting. 

When a portion of the ureter has been removed, the ureter is sewn back to the bladder as a neocystoureterostomy, with the anastomosis usually done over an indwelling double-J stent.  When the entire bladder is removed, the urinary tract is reconstructed using a urostomy.  When the vascular supply allows, an end sigmoid colon urostomy with a more proximal end bowel colostomy is our preference.  But when the IMA and left colic vessels have previously been transected, a colon conduit may not be possible.  In these cases, we perform an ileal conduit.

Post-operative Cares

Patients have been successfully managed with the enhanced recovery protocols after extensive abdominal surgery such as HIPEC.[39-41] it is logical that these same enhanced recovery protocols would add benefit to patients undergoing surgery for locally advanced and recurrent rectal cancer, and this is standard of care at our institution.

Outcomes

The single most important predictor of survival after surgical management of recurrent rectal cancer is the achievement of an R0 resection (no gross or microscopic evidence of disease).[35] When an R0 resection is achieved, the 5-year overall survival rate is 55-80% at 5 years compared to 11-50% when an R0 is not achieved.[14, 35, 42]

Controversies/Limitations

Sacrectomy

A systematic review of greater than 200 patients undergoing a sacrectomy for bony invasion reported a mortality rate of 2%, major morbidity rate of 52% and an R0 resection rate of 78%. R0 resection was associated with a median overall survival of 34 months. High sacrectomy has also been reported by single institution with a 100% R0 resection rate and major complications occurring in 56%.[43]

Major vascular involvement

While historically involvement of the aortoiliac axis was considered an absolute contraindication to surgery for recurrent rectal cancer, there were many single institution experiences reported suggesting that it is possible to offer these patients surgery with good outcomes.  This involves en bloc resection of the arterial and/or venous structures with the tumor and reconstruction when necessary.

External iliac or common iliac involvement will require autologous or synthetic graft interposition or a more distal crossover graft. These institutions report high rates of reoperation and early complications, but the graft patency rate is high and limb salvage is 100%.[44]

Re-recurrence

Recurrence of tumor in the pelvis is not uncommon following an initial resection for locally recurrent rectal cancer.  Generally, these patients would be treated with non-operative and multidisciplinary management.  However, a few centers have demonstrated the safety of re-resection in highly selected patients.  In these studies, 30-day mortality was 0%, R0 resection rates ranged from 33-60%, and 5 year overall survival occurred in 1/3 of patients.[45, 46]

Sciatic notch disease

Historically, involvement of the sciatic notch or sciatic nerve was a contraindication to surgery for locally recurrent rectal cancer.  However, highly specialized institutions have reported the results from en bloc resection of the sciatic nerve and or the lumbosacral plexus for tumors that extend laterally in this direction.[36, 47]

Oligometastatic disease

Historically, the presence of any metastatic disease was an absolute contraindication to surgery for locally recurrent rectal cancer.  However, with modern improvements in imaging, chemotherapy, and surgery, the presence of resectable metastatic disease is no longer considered a contraindication.[12] Surgical management of metastatic disease will be addressed in detail elsewhere.

There is no standard of care currently for resection of lung metastases in the setting of recurrent rectal cancer.  But the simultaneous resection of liver metastases in collaboration with pelvic exenteration has been described by the PelvEx Collaborative.  They report a 5 year overall survival of 55% when an R0 resection was achieved and 20% when there was a microscopic or grossly positive margin.[48]

Intraoperative Radiation Therapy

Intraoperative radiation therapy involves the delivery of a single fraction of radiation directly to any pelvic location where there is concern for a close negative margin or microscopic positive margin after surgical resection. In highly specialized and experienced centers, IORT is associated with improved local control.[42, 49]  And in a systematic review by Mirnezami et.al, IORT was associated with improvement in disease-free survival and even overall survival.[49]

Minimally invasive surgery

Minimally invasive surgical (MIS) techniques have been used for pelvic exenteration in the setting of recurrent rectal cancer.  When compared to open resection, an MIS approach is associated with a shorter duration of hospital stay and a lower overall morbidity.[50]  However, it should be noted that patients requiring open resection generally have more advanced tumors than those who can be offered an MIS approach.

Palliative Surgery

Resection for palliation in the setting of unresectable recurrent rectal cancer should be considered on a case-by-case basis and should be agreed upon by a multidisciplinary team.  This is usually limited to the consideration of a defunctioning stoma.  But some have described palliative exenteration.[51]

Summary

International surgeons have become bolder and continue to push boundaries with our surgical techniques allowing for wider resections for locally recurrent rectal cancer while maintaining acceptable morbidity and mortality.  It is crucial that we continue to maximize patient selection and only offer such operations to patients with an anticipated R0 resection.

We must continue to optimize the neoadjuvant treatment strategies based on evidence, and we need clear guidelines regarding the sequence, regimen, and duration of chemotherapy and radiation therapy prior to surgery.

We must also continue to report outcomes and predictors of outcomes to further improve patient selection.  And we must focus on patient reported outcomes to align our goals of multidisciplinary treatment with the patients’ expectations and acceptance of anticipated morbidities.

References

  1. Kapiteijn E, Marijnen CA, Colenbrander AC, Klein Kranenbarg E, Steup WH, van Krieken JH, et al. Local recurrence in patients with rectal cancer diagnosed between 1988 and 1992: a population-based study in the west Netherlands. Eur J Surg Oncol. 1998;24(6):528-35.
  2. Bouchard P, Efron J. Management of recurrent rectal cancer. Ann Surg Oncol. 2010;17(5):1343-56.
  3. Heriot AG, Byrne CM, Lee P, Dobbs B, Tilney H, Solomon MJ, et al. Extended radical resection: the choice for locally recurrent rectal cancer. Dis Colon Rectum. 2008;51(3):284-91.
  4. Räsänen M, Carpelan-Holmström M, Mustonen H, Renkonen-Sinisalo L, Lepistö A. Pattern of rectal cancer recurrence after curative surgery. Int J Colorectal Dis. 2015;30(6):775-85.
  5. Gao Z, Gu J. Surgical treatment of locally recurrent rectal cancer: a narrative review. Ann Transl Med. 2021;9(12):1026.
  6. Palmer G, Martling A, Cedermark B, Holm T. A population-based study on the management and outcome in patients with locally recurrent rectal cancer. Ann Surg Oncol. 2007;14(2):447-54.
  7. Steele SR, Chang GJ, Hendren S, Weiser M, Irani J, Buie WD, et al. Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer. Dis Colon Rectum. 2015;58(8):713-25.
  8. Young PE, Womeldorph CM, Johnson EK, Maykel JA, Brucher B, Stojadinovic A, et al. Early detection of colorectal cancer recurrence in patients undergoing surgery with curative intent: current status and challenges. J Cancer. 2014;5(4):262-71.
  9. Wieldraaijer T, Bruin P, Duineveld LAM, Tanis PJ, Smits AB, van Weert H, et al. Clinical Pattern of Recurrent Disease during the Follow-Up of Rectal Carcinoma. Dig Surg. 2018;35(1):35-41.
  10. Farhat W, Azzaza M, Mizouni A, Ammar H, Ben Ltaifa M, Lagha S, et al. Factors predicting recurrence after curative resection for rectal cancer: a 16-year study. World J Surg Oncol. 2019;17(1):173.
  11. Lai IL, You JF, Chern YJ, Tsai WS, Chiang JM, Hsieh PS, et al. The risk factors of local recurrence and distant metastasis on pT1/T2N0 mid-low rectal cancer after total mesorectal excision. World J Surg Oncol. 2021;19(1):116.
  12. Berri RN, Abdalla EK. Curable metastatic colorectal cancer: recommended paradigms. Curr Oncol Rep. 2009;11(3):200-8.
  13. Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br J Surg. 2013;100(8):E1-33.
  14. Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative. Cancers (Basel). 2022;14(5).
  15. Hartley A, Ho KF, McConkey C, Geh JI. Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol. 2005;78(934):934-8.
  16. Hoffmann KT, Rau B, Wust P, Stroszczynski C, Hünerbein M, Schneider U, et al. Restaging of locally advanced carcinoma of the rectum with MR imaging after preoperative radio-chemotherapy plus regional hyperthermia. Strahlenther Onkol. 2002;178(7):386-92.
  17. Kim YH, Kim DY, Kim TH, Jung KH, Chang HJ, Jeong SY, et al. Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer. Int J Radiat Oncol Biol Phys. 2005;62(3):761-8.
  18. Ryan JE, Warrier SK, Lynch AC, Heriot AG. Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. Colorectal Dis. 2015;17(10):849-61.
  19. Berger KL, Nicholson SA, Dehdashti F, Siegel BA. FDG PET evaluation of mucinous neoplasms: correlation of FDG uptake with histopathologic features. AJR Am J Roentgenol. 2000;174(4):1005-8.
  20. Antoch G, Vogt FM, Freudenberg LS, Nazaradeh F, Goehde SC, Barkhausen J, et al. Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology. Jama. 2003;290(24):3199-206.
  21. Ciliberto M, Maggi F, Treglia G, Padovano F, Calandriello L, Giordano A, et al. Comparison between whole-body MRI and Fluorine-18-Fluorodeoxyglucose PET or PET/CT in oncology: a systematic review. Radiol Oncol. 2013;47(3):206-18.
  22. Jimenez RE, Shoup M, Cohen AM, Paty PB, Guillem J, Wong WD. Contemporary outcomes of total pelvic exenteration in the treatment of colorectal cancer. Dis Colon Rectum. 2003;46(12):1619-25.
  23. Suzuki K, Dozois RR, Devine RM, Nelson H, Weaver AL, Gunderson LL, et al. Curative reoperations for locally recurrent rectal cancer. Dis Colon Rectum. 1996;39(7):730-6.
  24. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-46.
  25. Syk E, Torkzad MR, Blomqvist L, Ljungqvist O, Glimelius B. Radiological findings do not support lateral residual tumour as a major cause of local recurrence of rectal cancer. Br J Surg. 2006;93(1):113-9.
  26. Mishra N. Locally Recurrent Rectal Cancer. Dis Colon Rectum. 2018;61(6):651-4.
  27. Denost Q, Frison E, Salut C, Sitta R, Rullier A, Harji D, et al. A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer – GRECCAR 15 trial protocol. Colorectal Dis. 2021;23(7):1909-18.
  28. Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II). BJS Open. 2021;5(3).
  29. Valentini V, Morganti AG, De Franco A, Coco C, Ratto C, Battista Doglietto G, et al. Chemoradiation with or without intraoperative radiation therapy in patients with locally recurrent rectal carcinoma: prognostic factors and long term outcome. Cancer. 1999;86(12):2612-24.
  30. Valentini V, Morganti AG, Gambacorta MA, Mohiuddin M, Doglietto GB, Coco C, et al. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study. Int J Radiat Oncol Biol Phys. 2006;64(4):1129-39.
  31. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv263.
  32. Das P, Delclos ME, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, et al. Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation. Int J Radiat Oncol Biol Phys. 2010;77(1):60-5.
  33. Tanis PJ, Doeksen A, van Lanschot JJ. Intentionally curative treatment of locally recurrent rectal cancer: a systematic review. Can J Surg. 2013;56(2):135-44.
  34. Steenhagen E. Preoperative nutritional optimization of esophageal cancer patients. J Thorac Dis. 2019;11(Suppl 5):S645-s53.
  35. Lau YC, Brown KGM, Lee P. Pelvic exenteration for locally advanced and recurrent rectal cancer-how much more? J Gastrointest Oncol. 2019;10(6):1207-14.
  36. Solomon MJ. Redefining the boundaries of advanced pelvic oncology surgery. Br J Surg. 2021;108(5):453-5.
  37. Sagebiel TL, Faria SC, Aparna B, Sacks JM, You YN, Bhosale PR. Pelvic reconstruction with omental and VRAM flaps: anatomy, surgical technique, normal postoperative findings, and complications. Radiographics. 2011;31(7):2005-19.
  38. Johnson YL, West MA, Gould LE, Drami I, Behrenbruch C, Burns EM, et al. Empty pelvis syndrome: a systematic review of reconstruction techniques and their associated complications. Colorectal Dis. 2022;24(1):16-26.
  39. Dhiman A, Fenton E, Whitridge J, Belanski J, Petersen W, Macaraeg S, et al. Guide to Enhanced Recovery for Cancer Patients Undergoing Surgery: ERAS for Patients Undergoing Cytoreductive Surgery with or Without HIPEC. Ann Surg Oncol. 2021;28(12):6955-64.
  40. Lu PW, Fields AC, Shabat G, Bleday R, Goldberg JE, Irani J, et al. Cytoreductive Surgery and HIPEC in an Enhanced Recovery After Surgery Program: A Feasibility Study. J Surg Res. 2020;247:59-65.
  41. Webb C, Day R, Velazco CS, Pockaj BA, Gray RJ, Stucky CC, et al. Implementation of an Enhanced Recovery After Surgery (ERAS) Program is Associated with Improved Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol. 2020;27(1):303-12.
  42. Haddock MG. Intraoperative radiation therapy for colon and rectal cancers: a clinical review. Radiat Oncol. 2017;12(1):11.
  43. Dozois EJ, Privitera A, Holubar SD, Aldrete JF, Sim FH, Rose PS, et al. High sacrectomy for locally recurrent rectal cancer: Can long-term survival be achieved? J Surg Oncol. 2011;103(2):105-9.
  44. Peacock O, Smith N, Waters PS, Cheung F, McCormick JJ, Warrier SK, et al. Outcomes of extended radical resections for locally advanced and recurrent pelvic malignancy involving the aortoiliac axis. Colorectal Dis. 2020;22(7):818-23.
  45. Harji DP, Sagar PM. Advancing the surgical treatment of locally recurrent rectal cancer. Br J Surg. 2012;99(9):1169-71.
  46. Colibaseanu DT, Mathis KL, Abdelsattar ZM, Larson DW, Haddock MG, Dozois EJ. Is curative resection and long-term survival possible for locally re-recurrent colorectal cancer in the pelvis? Dis Colon Rectum. 2013;56(1):14-9.
  47. Sakata S, Karim SM, Mathis KL, Kelley SR, Rose PS, Dozois EJ. Posterior-First Two-Stage Approach to En Bloc Resection of Locally Recurrent Rectal Cancer Involving the Pelvic Sidewall. Dis Colon Rectum. 2021;64(8):e465-e70.
  48. van Ramshorst G. Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative. Colorectal Dis. 2020;22(10):1216.
  49. Mirnezami R, Chang GJ, Das P, Chandrakumaran K, Tekkis P, Darzi A, et al. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol. 2013;22(1):22-35.
  50. Minimally invasive surgery techniques in pelvic exenteration: a systematic and meta-analysis review. Surg Endosc. 2018;32(12):4707-15.
  51. Palliative pelvic exenteration: A systematic review of patient-centered outcomes. Eur J Surg Oncol. 2019;45(10):1787-95.