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41 Rectal Cancer: Watch andWait

325

Rectal Conditions: Rectal Cancer—Postoperative Surveillance

DanielI.Chu andGregoryD.Kennedy

Refer toAlgorithm in Fig.42.1

A. Postoperative surveillance for rectal cancer

involves four modalities: the clinical exam, laboratory tests, endoscopy and imaging. These modalities are also used in postoperative surveillance for colon cancer. The goals of surveillance are (1) to detect recurrent disease that may be potentially resectable and (2) to identify and remove metachronous lesions at an early stage. Compared to colon cancer, rectal cancer is at signicantly higherrisk for local-regional and distant recurrence with estimates ranging from 5–15%. Studies show that 95% of recurrences, however, occur within 5-years after surgical resection. Surveillance is therefore uniformly recommended up to 5-years post-resection. Controversy remains, however, on how best to coordinate surveillance modalities. Certain conditions, such as locally-advanced rectal cancer, may require higher intensity surveillance while others, such as a well-localized stage 1 rectal cancer, might only require lowintensity surveillance. Future research is needed to clarify these details but the current

D. I. Chu (*) · G. D. Kennedy Division ofGastrointestinal Surgery, Department ofSurgery, University ofAlabama at Birmingham, Birmingham, AL, USA e-mail: dchu@uab.edu

surveillance algorithm(s) allow for some individualization of these decisions.

B. Surveillance begins with the clinical exam.

The goal is to identify new symptoms such as bleeding, pain, or constipation using the history/physical examination which may prompt further testing. The National Comprehensive Cancer Network (NCCN) Guidelines currently recommend H&Ps every 3–6months for the rst 2-years and every 6months for the remainder 3years presuming no positive ndings for more advanced rectal cancers (stage 2–4). Studies have suggested that a symptoms- based approach to further testing (waiting until symptoms develop before directed testing) does not result in a signicant survival disadvantage compared to more intensive surveillance strategies. Patients undergoing symptoms-based surveillance did, however, undergo fewer curative-intent surgeries compared to more intensively surveilled patients. A recent meta-analyses of 11 randomized-control trials (RCTs) favored intensive surveillance by observing improved overall survival, shorter time to detection of asymptomatic recurrent disease and more curative-intent surgeries. Cancer-specic survival, however, was not signicantly different for patients undergoing intensive or nonintensive surveillance. Until further studies clarify these controversies, H&Ps remain a

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D. I. Chu and G. D. Kennedy

Fig. 42.1 Recommended algorithm for postoperative surveillance for rectal cancer. Surveillance begins after surgical staging (A) and uses the clinical exam (B), laboratory studies (C), endoscopic tests (D) and imaging (E). Other modalities (F) such as PET/CT and FIT/fecal DNA

constant on all surveillance recommendations and are a reasonable, low-cost start to any surveillance strategy.

C. Laboratory studies used in rectal cancer sur-

veillance currently focus on measuring the tumor marker carcinoembryonic antigen (CEA). An elevation in CEA level, compared to a baseline pre-treatment measurement, warrants further investigation for recurrent and metastatic disease. The frequency of postresection CEA measurements parallels the post-surveillance H&P schedule: every 3–6months for the rst 2-years and then every 6-months for the remainder 3-years for stage 2–4 rectal cancers (5). Studies support the benets of frequent CEA testing including earlier detection of recurrent disease and more opportunities for curative- intent surgery.

D. Endoscopic surveillance includes colonos-

copy and proctoscopy. The primary goal of colonoscopic surveillance is to detect and remove metachronous polyps as colorectal cancer patients are at higher-risk for second colorectal cancers. For all stages of rectal cancer, the NCCN and US Multi- Society Task Force recommend colonoscopy at 1-year post-resection to evaluate for recurrent or

testing are not recommended in primary surveillance strategies. If surveillance reveals a positive nding(s), then further workup is necessary (G). noscopies recommended at 5-year intervals if no abnormal ndings; CAP chest abdomen pelvis

∗

Additional colo-

metachronous disease. If no colonoscopy was performed before surgery, then a closer follow-up colonoscopy is recommended 3–6months after surgery. If the 1-year colonoscopy is normal, then the next recommended colonoscopy is not required for an additional 3years. If the 3-year colonoscopy is normal, then subsequent colonoscopies should occur at 5-year intervals. If at any point a high-risk adenoma such as a villous or highgrade dysplastic lesion or a polyp >1 cm is detected and removed, follow- up colonoscopies should be obtained at annual intervals or at recommended polyp surveillance intervals. The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) Guidelines differ slightly and recommend colonoscopies at 1-year post-resection and then every 5-years as dictated by ndings. Proctoscopy was previously included in standard post-resection surveillance to evaluate for low anastomotic recurrence, but the NCCN removed this recommendation in 2015 due to the rare incidence of isolated local recurrences. Proctoscopy is recommended, however, for endoscopic surveillance after transanal excisions of rectal cancers.

42 Rectal Conditions: Rectal Cancer—Postoperative Surveillance

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E. Radiographic imaging is a critical piece of

post-treatment rectal cancer surveillance. Computer tomography (CT) is most familiar to clinical practice and the cornerstone of this surveillance algorithm. The primary goal of a CT chest, abdomen and pelvis (CAP) with IV contrast is to detect metastatic disease in the lungs and liver and to determine their potential resectability. The NCCN recommends a CT surveillance schedule that follows a pattern identical to H&P and CEA levels but differs by staging. For stage 2–3 rectal cancer, CT CAPs should be obtained every 6–12 months for 5 years total. For stage 4 rectal cancer, CT CAPs should be obtained every 3–6 months for the rst 2 years before spacing out to every 6–12 months for the remaining 3 years. The ASCO/CCO guidelines differ slightly with a less-intensive schedule and recommend CT scans annually for 3-years post-resection.

F. Other surveillance modalities such as

positron- emission tomography (PET) are not recommended in primary surveillance strategies. PET may be most useful, however, after detection of equivocal lesions or in the setting of an elevated CEA with negative, high- quality CT scans. Fecal immunochemical tests (FIT) and fecal DNA testing are also not recommended as surveillance tools due to insufcient evidence at this time supporting their utility for post-resection surveillance.

G. When surveillance modalities detect possible

recurrent or new disease the patient requires a full staging workup. The available modalities remain the same. For elevated CEA levels, the workup includes H&P, endoscopic and radiographic studies. For isolated pelvic recurrence or metachronous lesions, the treatment will depend on whether the lesion is resectable versus non-resectable. It is clear that a multidisciplinary approach to recurrent rectal cancer is necessary. However, a full discussion of the management of this complicated situation is beyond the scope of this chapter.

Recurrent Rectal Cancer

IanWhite andShmuelAvital

Introduction

Until late in the twenty-rst century, the local recurrence rate after rectal cancer surgery was approximately in excess of 20% and occasionally as high as 50%. With the introduction of the total mesorectal excision (TME) surgical technique by Professor Bill Heald in England, as well as the use of neoadjuvant chemo-radiotherapy in Northern Europe (The Dutch trial), the local recurrence rate signicantly decreased to below 5%.

Metastatic disease is most commonly seen in the liver and lungs, and aggressive radical surgery is well accepted and has shown to be successful in increasing survival. Local recurrent disease is dened as the recurrence of adenocarcinoma in the pelvis following previous rectal cancer surgery. Treatment involves radical surgery and is often very complicated. Cure rates have improved in recent years (50% between 2005 and 2012 compared to 32% between 1988 and 1996) with multimodal therapy and dedicated teams.

I. White Meir Medical Center, Kfar Saba, Israel

Department ofSurgery B, Meir Medical Center, Kfar Saba, Israel

S. Avital (*) Department ofSurgery B, Meir Medical Center, Kfar Saba, Israel

In this chapter, we will discuss the factors associated with local recurrence, its detection, as well as metastases and their treatment options and prognosis.

Risk Factors Associated withLocal Recurrence

Multiple risk factors have been identied and include tumor-specic features, patient-related issues, surgical technique, and institutional/ departmental knowledge and multidisciplinary expertise.

Advanced tumor stage, poor differentiation, and lymphovascular and perineural invasion as well as lower, bulkier, macroscopically inltrating tumors are all associated risk factors. Male patients with narrower, longer pelvises and those who are obese patients have been linked to worse outcomes, most probably due to a more demanding surgical resectability. Surgeon experience has also shown to be a prognostic factor with higher caseloads in higher volume centres (over 10–12 rectal cancer cases/year) and a higher frequency of sphincter saving procedures and properly administered neoadjuvant therapy resulting in lower recurrence rates. Such examples are the recurrence rates of 4% in the higher volume centers versus 10% in the lower volume centers, as reported in the Stockholm trial.

Today’s principles of sharp TME dissection should be practiced by all surgeons, as well as

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I. White and S. Avital

knowledge of proper distal and proximal margins and, most importantly, the circumferential resection margin (CRM), which has been proven as perhaps the most important factor predictive of local recurrence and survival.

Lateral clearance of <1 mm (positive CRM) results in a signicantly higher likelihood for recurrence (3.5 times) and signicantly reduced survival (5-year survival: 29% vs. 72%, positive vs. negative CRM).

Conversely, in the early era of TME, abdominoperineal resection (APR) was associated with higher recurrence rates, until the issue of “coning” in lower tumors was overcome and a return to traditional APR (Fig.43.1), leading to a lower risk of CRM positivity and rectal/tumor perforation.

The index surgery has a bearing on the type of recurrence and the subsequent ability for salvage. As compared to sphincter sparing surgery followed by anastomotic and perianastomotic recurrences, recurrences following APR are in a signicantly more violated pelvis and across much wider areas. Ironically, in procedures with insufcient TME, salvage surgery is more successful, most likely due to the time taken to reach nonresectable tissue and the surgeon’s ability to remove the recurrence in the mesorectum. Recurrence at the anastomosis or perianastomotic tissue has a more favorable outcome as it is easier to diagnose following digital rectal examination, endoscopy, and biopsy; symptoms manifest much earlier. Following APR, the pelvic tissue has been more extensively violated leading to a higher probability of sidewall and pelvic inltration, making curative surgical treatment more challenging.

Local recurrence may also be noted following with or without local excision, pre and/or or postoperative chemoradiotherapy, and/o radiotherapy.

Furthermore, local recurrence may be noted after initially successfully complete response and “wait and watch” protocol. Early publications have shown excellent salvage surgery rates if a re-growth diagnosed early and the appropriate surgery is performed. The concept is that if surgery (TME) for a re-growth is immediately performed, survival rates should be comparable to rates after index surgery.

Fig. 43.1 Extralevator APR versus conventional APR.Right side dotted line shows dissection close to the tumour leading to increased positive CRM and tumour/ rectal perforation as opposed to dissection on left hand side leading to clearer margins and decreased local recurrence

Refer to Algorithm in Fig. 43.2

Follow-upandInitial Assessment

In order to diagnose both local and distal recurrence, follow-up must be regimented and proven to be effective. Multiple studies have shown the importance of follow-up, especially within the rst 2 years post surgery/treatment. There is obvious diversity among institutions around the world; Table 43.1 summarizes the most recent recommendations based on individual international organisations.

Pelvic recurrence is a complicated oncological, surgical, and multidisciplinary entity; sal-

43 Recurrent Rectal Cancer

333

Fig. 43.2 Algorithm for management of recurrent rectal cancer

vage therapy offers the only potential for cure and preservation of quality of life. It is not surprising that, with the variation of access to specialist centres and the variety of treatment options worldwide, there is a wide range in outcomes. Median survival ranges from 22 to 60months, 3-year local control rates range between 26% and 100%, and the 5-year distant failure rates range from 9% to 68%. Some confounders in these variable outcomes include heterogeneity of disease, previous therapies, and underlying tumor biology.

If local recurrence is suspected, further inves-

tigation is warranted. Often, the rst suspicious

symptom is either a clinically-related complaint or an increased CEA.Bleeding, pain, or obstructive symptoms are the most common complaints. Although CEA represents a glycoprotein oncofetal tumor associated antigen being expressed by more than 90% of colorectal adenocarcinomas, it is not increased in the serum of more than 90% of patients with primary rectal cancer. As a marker, it is used to monitor treated patients for recurrent disease. Sensitivity and specicity of CEA as a marker during follow-up ranges from 43% to 98% and 70% to 90%, respectively. Both its absolute value and increase over time should prompt further investigations.

334

I. White and S. Avital

Table 43.1 Published colorectal surveillance guidelines

History and physical

ASCO (Stage II/ III)

NCCN (Stage I–III)

ASCRS (Stage I–III)

UK (Stage I–III)

ASCO American Society of Clinical Oncology. ASCRS American Society of Colon and Rectal Cancer Surgeons. CEA carcinoembryonic antigen, NCCN National Comprehensive Cancer Network, UK United Kingdom 2010 Guideline. (Modied from Optimal post-treatment surveillance in cancer survivors: is more really better? Shah M, Denlinger CS.

Oncology (Williston Park). 2015 Apr;29(4):230–40)

Every 3–6months×3years; every 6months at years 4 and 5

Every 3–6months×2years; every 6months in years 3–5

At least every 4months for 2years

None CT of abdomen and

CT (chest/abdomen/ pelvis) CEA Colonoscopy

Annually×3years if high risk

Annually for up to 5years, especially if high risk

None At least every 4months

pelvis only, once within 2years

Every 3months for at least 3years

Every 3–6months×2years; every 6months in years 3–5

for 2years None Every 5years

At 3years and then every 5years thereafter

At years 1 and 4, then every 5years

Every 3years

Currently, CT scan, uoro-deoxy-glucose positron emission tomography (FDG)-PET/CT scan, MRI, and a host of other diagnostic tools are used to further evaluate and identify recurrences. CT correctly diagnoses recurrence in approximately 76% of patients, although there are a signicant number of false positives. FDG- PET scan is an accurate modality for detecting pelvic recurrence and may have advantages over CT and MRI scan in differentiating scar tissue from viable tumor. The reported accuracy ranges from 74% to 96%. Nevertheless, it has certain limitations including inability to detect small lesions, mucinous tumors, and small positive lymph nodes. MRI is an excellent modality for detection and is highly recommended due to its excellent soft-tissue resolution. Distal intra- luminal recurrence can be identied by rectal digital examination and more proximal recurrence by endoscopy.

A–C.

Figure 43.2 is the algorithm we have developed for the assessment of retreatment of recurrent rectal cancer. The rst step (A) is assessment, which occurs either naturally during follow-up or out of necessity if clinically warranted.

When assessment is completed, including further radiology if a recurrence is located, either locally, then a tissue biopsy is needed (B).

Different modalities can be employed depending on location.

Finally, the patient must be assessed for tness for surgery, including functional status and quality of life (C). Assessment by other specialists including for example a cardiologist, neurologist or lung specialist with echocardiogram, stress test, carotid Doppler or lung function tests may be needed.

D.Local Recurrence (See Fig.43.2)

Classication ofLocal Recurrence

Many authors have attempted to classify local recurrence using various methods, with anatomical location being the most popular. Although there are a variety of methods, most are similar to a Netherlands group that suggested the following according to imaging: (1) presacral: predominantly midline, in contact with the sacral bone, (2) posterolateral: laterally located, near to or invading the piriformis muscle, in contact with the sacral bone, (3) (antero)lateral: laterally located, in association with anterior organs or along the iliac vessels or in the obturator lymph node compartment, (4) anterior: predominantly midline, involving bladder, uterus, vagina, seminal vesicles, or prostate, (5) anastomotic: midline, after low anterior resection, low Hartmann procedure, or local excision, at the staple line, (6)

43 Recurrent Rectal Cancer

335

perineal: midline, perineum, or anal sphincter complex with surrounding perianal and ischiorectal space, or (7) other location. Their results, subsequently veried by others, showed a direct correlation with the site of recurrence with R0 resections achieved in 54% of the patients, and 5-year cancer- specic survival was 40.5%. The worst outcomes were seen in presacral locally recurrent rectal cancer (LRRC), with only 28% complete resections and 19% 5-year survival (P=0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable outcomes, with 77% R0 resections and 60% 5-year survival (P=0.04). Generally, if a complete resection was achieved, survival improved, except in postero-

lateral LRRC.Local re-recurrence and metastasis rate were lowest in anastomotic LRRC.

Although TME has dramatically improved management of rectal cancer, its popularity decreases the likelihood that a recurrent neoplasm will remain conned to a specic compartment due to the absence of visceral rectal fascia.

An alternate system used at the Mayo Clinic classied these tumours based on the presence of symptoms, with a particular focus on pain, as well as the degree of xation. Figure 43.3 shows an example of the classication of locally recurrent rectal cancer.

bPR

aPR

Fig. 43.3 Classication of locally recurrent rectal cancer. The pelvis can be divided into seven compartments: (a) peritoneal reection (PR); (b) above PR (aPR), below

PR (bPR); (c, d) central (C), posterior (P), lateral (L), inferior (!) (www.aibolita.com)

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