The terms typically used to describe pathologic margins for cancer resections are defined below

(Table 14-9). An R0 margin is typically considered negative and an R2 margin is considered grossly

positive. For many, but not all, types of cancer, the presence of an R1 margin is associated with

increased risk of recurrence. Management of a positive pathologic margin is dependent on technical and

oncologic factors associated with that particular tumor. For instance, some early-stage cutaneous

malignancies such as dermatofibrosarcoma protuberans or basal cell cancer are characterized by limited

risk of distant disease dissemination and a high risk of local recurrence in the setting of positive

pathologic resection margins. In a location where additional local excision may not be limited by

adjacent structures, an effort for reexcision of a positive margin may be reasonable. Alternatively, the

presence of cancer at the superior mesenteric artery (SMA) resection margin at the time of

pancreaticoduodenectomy does not lead to an additional operative attempt to achieve a negative final

margin for patients with pancreas adenocarcinoma. The hesitation to attempt reresection is driven not

only by the technical challenges of attempting to achieve a broader margin along the SMA, but also by

the very high risk of distant recurrence for those patients and the relatively lower impact of local

recurrence in this setting.123–125

Lymphadenectomy

The removal of regional lymph nodes at the time of resection of the primary tumor has been the focus

of significant investigation and controversy throughout the contemporary history of surgical

management of cancer. The surgical principles attributed to William Halsted regarding the surgeon’s

role in interrupting the progression of cancer from the primary tumor through lymphatic channels to

regional lymph nodes and then to distant sites form the traditional rationale for regional

lymphadenectomy.126,127 However, more contemporary studies such as MSLT-1, the Dutch Gastric

Cancer Lymphadenectomy, and ACOSOG Z0011 clinical studies have raised questions regarding the

survival benefit of lymphadenectomy for patients with melanoma, gastric cancer, and breast cancer,

respectively.128–131

The potential prognostic benefits of lymphadenectomy undoubtedly are more germane than

therapeutic advantages. For almost all types of malignancy, the presence of cancer within regional

lymph nodes portends a worse prognosis for patients, as a harbinger of systemic cancer spread. The

accuracy of the assessment of the regional lymph node basin can be increased with either focused

evaluation of the most at-risk lymph nodes (i.e., sentinel lymph node biopsy) or thorough sampling of a

large number of nodes (i.e., lymphadenectomy). Accuracy of cancer staging, for example in colorectal

cancer, is oftentimes increased through the sampling of a sufficient number of lymph nodes. The

threshold for quality assurance through adequate lymph node sampling has been established for

surgeons who perform colorectal cancer resections, however, that well-defined performance metric is

not common to all types of resection and all types of cancer.132–135

For patients with bulky involved regional lymph nodes, the benefits of node removal are not likely

prognostic. In selected patients, removal of these lymph nodes may provide some palliation from local

symptoms. The role of “prophylactic palliation” or removal of lymph nodes, which may develop and

cause local problems is less clear. For example, in melanoma or rectal cancer, eliminating all of the

regional lymph nodes in the setting of positive microscopic nodal burden decreases the potential of

future development of bulky, symptomatic nodes.128,136–138 The therapeutic benefit of avoiding local

recurrence in a subset of the operative population needs to be balanced against the potential adverse

effects of lymphadenectomy. For many nodal basin sites, the adverse impact of interrupting lymphatic

flow can have significant deleterious effects on patients following lymphadenectomy, including

lymphedema, paresthesias, and even development of secondary malignancies, such as angiosarcoma

(Stewart–Treves syndrome).139–142

In general, lymphadenectomy is an important aspect of surgical cancer care when any of the

following criteria are met: (1) removal of regional lymph nodes will provide important information to

either guide adjuvant therapy decisions or provide prognostic clarity (e.g., colon cancer, gastric cancer);

(2) lymphadenectomy can eliminate a predictably involved site of disease involvement which can lead

to local regional complications in the setting of nodal recurrence (e.g., rectal cancer, esophageal

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cancer); (3) removal of at-risk lymph nodes is a minor adjunct of the procedure for primary tumor

removal (e.g., pancreatectomy). The extent of our operative management for cancer is likely to change

as we learn more about the therapeutic benefit of regional nodal removal. Perhaps more strikingly, the

prognostic information gained by evaluating a nodal basin is likely to diminish as our ability to profile

tumors and their behavior becomes more dependent on genomic, proteomic, and other expression

profiling.

Resection of Metastatic Disease

Outside the palliative setting, the indications for resection of metastatic disease are relatively narrow.

Despite the growing awareness and increased frequency of resection for metastatic colon cancer,

endocrine tumors, and gastrointestinal stromal tumors, the vast majority of patients with metastatic

disease are not eligible for metastasectomy. Although it is important to recognize the diverse spectrum

of presentations for malignant disease and to be wary of absolute contraindications against surgical

management of metastases, several general principles do apply to the overwhelming majority of

patients with metastatic disease.

Complete elimination of all sites of disease is generally associated with dramatically improved

survival compared to incomplete resection. In addition, the outcomes for patients with incompletely

resected disease are frequently comparable to outcomes for patients who underwent no resection at

all.108–110,143–145 For these reasons, resection or ablation of all sites of disease is a common requirement

when making a decision to proceed with resection of metastatic disease. This principle applies to

patients with primary tumors in place as well; therefore, patients with unresectable primary tumors are

generally not eligible for curative intent resection of their metastatic sites.

The behavior or biology of an individual’s cancer may suggest a less aggressive phenotype and

warrant consideration of metastasectomy. Oftentimes characteristics of favorable cancer biology are

associated with improved survival outcomes following resection. A prolonged period of progression-free

survival (PFS) or DFS is commonly associated with improved outcomes following resection of

metastatic disease.143–145 Progression of metastatic sites while receiving first-line systemic

chemotherapy is often a harbinger of early systemic failure among patients undergoing resection of

metastatic disease.146,147 As systemic chemotherapy has grown more effective over the last decades, the

impact on tumor progression and control of systemic disease has led to increased opportunities for

resection of metastatic sites. This concept has been most plainly demonstrated in the context of hepatic

colorectal metastases. The frequency of hepatectomy in that setting has increased in harmony with the

increased effectiveness and availability of both cytotoxic and targeted chemotherapy agents.122 Surgical

management of metastatic disease may increase in frequency for other diseases as we develop more

effective systemic therapy options.

Cancer-Related Surgical Outcomes

The short-term outcomes for surgical patients commonly include metrics, such as complication rates,

length of stay, mortality rate, and overall survival (OS). These metrics are certainly important measures

of quality and efficacy for patients undergoing operations for cancer. Similar to other surgical

specialties, cancer-related surgery also carries specific outcome measures, which are particularly

relevant to these clinical scenarios. Understanding these metrics is critical to balancing risk and benefit

for individual patients as well as for evaluating the role of new therapeutic strategies and approaches.

Disease Recurrence

Many surgical specialties are directed at the eradication of a tangible, anatomically identifiable lesion.

Peripheral and coronary vascular bypass, gastroesophageal fundoplication, and parathyroidectomy are

all measured by how effectively the treatment eliminates the arterial plaque, gastroesophageal reflux,

or hyperparathyroidism. Early recurrence of the condition suggests a failure of therapy or poor patient

selection for the procedure. Disease recurrence is also a critical measure of the effectiveness of surgical

therapy for cancer patients.

A prerequisite for disease recurrence as a measure of outcome is the initial eradication of all visible

cancer. Recurrence can be measured by development of symptoms, physical examination, radiographic

evaluation, biochemical evaluation, or operative exploration. Unique to the practice of surgery for

cancer patients is the distinction between locoregional and distant disease recurrence. Locoregional

recurrence is typically defined as recurrence in the resection bed or region of the draining regional

lymph nodes. Distant recurrence is typically defined as occurrence of malignant cells outside of the

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initial primary tumor and lymphadenectomy resection field.

Although resection is traditionally considered a means to achieve locoregional control, and adjuvant

systemic therapy is employed to control distant disease recurrence, a decision to proceed with an

operation should consider how the operation impacts both locoregional and distant recurrence. A wellperformed, radical, margin-negative operation can only lead to prolonged DFS if it is performed with

appropriate patient selection. This distinction is the underpinning behind the approach for patients with

small-volume metastatic disease in the setting of pancreatic adenocarcinoma, gastric cancer, or biliary

tract cancers. Many patients, when faced with this scenario, will ask their surgeon, “Why can’t you just

take out all of it?” Patients with easily resectable, distant disease are poor candidates for resection not

because they cannot be rendered free of all visible disease but rather because the findings of metastases

are highly predictive of early distant disease recurrence even if local control can be achieved. The tradeoff for a short period of DFS after a radical operation is the chance at a more prolonged PFS or OS with

the immediate initiation of effective systemic chemotherapy.

Progression-Free Survival

For patients who cannot have all visible tumor resected due to locally advanced disease or metastases,

PFS is an important measure for subsequent therapy. The propensity for a treatment to control, but

perhaps not eliminate, a measurable volume of tumor is the critical measure for defining the

effectiveness of that therapy. For many types of cancer, PFS is a reliable surrogate for OS.148,149

Typically, when patients experience disease progression while receiving a particular regimen of

systemic therapy, the treating physician will consider initiating the next line of systemic treatment.

Radiographic progression of measurable lesions is measured by a well-defined set of criteria referred

to as RECIST or modified RECIST criteria. Response Evaluation Criteria in Solid Tumors (RECIST) was

developed in 2000 and subsequently modified in 2009 as a system for measuring tumor response or

progression.150 These criteria are commonly employed in clinical trials as a standardized way to

determine when a tumor has progressed on therapy. A simplified description of the criteria is included

in Table 14-10. This strategy requires the upfront identification of index lesions, which are measurable

radiographically. RECIST has proven to be a useful measure of potential treatment benefit in phase II

clinical trials. Although useful in clinical trials, stringent application of RECIST measures of progression

is not as readily used outside trial settings. Even small changes in the one-dimensional measurements or

characteristics of measurable lesions may be considered evidence for clinical progression and

justification for a change in treatment course.

Return to Intended Oncologic Treatment

A novel measure for the quality of surgical management of cancer patients is return to intended

oncologic treatment (RIOT).151 This metric considers the place that resection holds in the

multidisciplinary care of a cancer patient. Although surgical resection is required for a curative intent

pathway for the majority of solid tumors, important oncologic adjuncts such as adjuvant chemotherapy,

radiotherapy, and maintenance hormonal therapy can reduce the chances of recurrence and prolong

survival for many patients. Delays or disqualifications due to operative adverse events may negatively

impact the overall outcomes of patients. An important element in the assessment of the quality of

cancer care is the ability for a health system to deliver all of the treatment modalities demonstrating

benefit for a particular malignant condition. Recognizing that the definitive resection of a cancer is part

of a larger treatment strategy is one of the important considerations for assessing surgical outcomes for

patients with cancer.

Table 14-10 Common Criteria Used to Determine Therapy-Related Progression

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