General Principles of Wide Resection of Bone Tumors

Joshua M. Lawrenz, MD, FAAOS

Nathan W. Mesko, MD, FAAOS, FAOA

Dr. Lawrenz or an immediate family member serves as a board member, owner, officer, or committee member of Musculoskeletal Tumor Society. Dr. Mesko or an immediate family member is a member of a speakers’ bureau or has made paid presentations on behalf of ONKOS Surgical and Stryker; serves as a paid consultant to or is an employee of Bone Support, ONKOS Surgical, and Stryker; and serves as a board member, owner, officer, or committee member of Musculoskeletal Tumor Society. Neither Dr. Lawrenz nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT

The primary goal in the surgical management of primary malignant bone tumors is wide resection to obtain local cure. A comprehensive understanding of preoperative advanced imaging and features specific to each sarcoma type and anatomic location is paramount toward achieving a negative margin resection. Emerging advanced technology has been introduced in recent years to further improve oncologic outcomes with the aim of improving resection accuracy. After tumor resection, the secondary goal is to provide a durable reconstruction to alleviate pain and restore function. In most cases, limb salvage can be achieved. Reconstruction options include endoprosthesis, allograft-prosthetic composite, osteoarticular allograft, intercalary allograft, vascularized autograft, resection arthroplasty, arthrodesis, rotationplasty, bone transport, and amputation. The reconstructive method should be applicable to the patient’s age, functional capacity, prognosis, and wishes, allowing for a long-lasting and functional construct.

INTRODUCTION

The surgical management of primary malignant bone tumors consists of two goals: local oncologic control and reconstruction. Although these two phases of treatment are related, it is helpful to differentiate them for the purposes of understanding their relative priority. The foremost aim in the surgical management of malignant primary bone tumors is local oncologic control. Before the 1970s, amputation was almost exclusively performed to obtain local cure, although poor survival rates persisted (15% to 20%). In the 1980s, however, the introduction of adjuvant chemotherapy led to substantial improvements in survival because of the reduction in systemic disease burden, allowing for a shift in emphasis in surgical management from amputation toward limb-sparing resection techniques. After successful resection of a tumor, the secondary aim of surgical management is functional and long-lasting reconstruction. This two-phased approach, termed limb salvage surgery, is the standard of care when both local control and reconstructive goals are attainable at a level equivalent to or better than amputation.

MARGINS

Definitions

In 1980, surgical margins were defined as intralesional, marginal, wide, or radical¹ (Table 1). Intralesional resection is within the tumor. Marginal resection is within the reactive tissue immediately surrounding the tumor. Wide resection is through normal tissue completely encompassing the tumor. Radical resection removes the entire anatomic compartment in which the tumor is located. Malignant bone tumor resection is accomplished through wide resection of the tumor mass, with a margin or cuff of normal tissue surrounding the tumor (Figure 1). There is variability in how margins are defined and reported, and questions remain about the adequacy of the margin required.² Much of the debate surrounding margin controversy involves the importance of surgically entering into the reactive or edema zone during effective neoadjuvant/adjuvant therapies. In soft-tissue sarcoma, comparisons of margin width (<1 mm, 1 to 5 mm, >5 mm) have shown no difference in local recurrence or overall survival, although it is widely thought that the quality of the margin is as important as its size.³^,⁴ Traditionally, the treatment of bone sarcoma focused on the importance of a 3-cm longitudinal bony margin and a named soft-tissue layer surrounding the resected tumor. However, in locations such as the foot or hand, pelvis, spine, or any area involving an active physis, this is not a pragmatic margin goal. The literature has demonstrated no worse oncologic outcome with longitudinal bony resection margins of 1.5 cm in extremity sarcoma.⁵ Despite the lack of consensus regarding specific margin distance, one meta-analysis reemphasized the basic principle of reduced local recurrence rates with negative margins.⁶ Not infrequently, vital neurovascular structures may be immediately adjacent to the tumor, where wide resection would mandate sacrifice of these. In soft-tissue sarcoma, it has been shown to be safe and acceptable to perform a planned marginal resection (through the reactive tissue around the tumor, not the tumor itself) with effective adjuvant radiation therapy or chemotherapy, without increased risk of local recurrence at 10 years.⁷ Similar principles have been applied to bone sarcoma soft-tissue mass extensions and planned marginal margins.

Table 1 Margin Classification Systems

*System*	*Description*
Enneking MSTS classification of musculoskeletal sarcoma
Intralesional	Resection within tumor (positive)
Marginal	Resection through reactive tissue around tumor (positive)
Wide	Resection through normal tissue around tumor (negative)
Radical	Resection of entire compartment containing tumor (negative)
Birmingham classification of primary high-grade osteosarcoma
1a	Tumor necrosis ≥90% and margins >2 mm; 5-yr LRFS = 98.6%
1b	Tumor necrosis ≥90% and margins ≤2 mm; 5-yr LRFS = 91.7%
2a	Tumor necrosis <90% and margins >2 mm; 5-yr LRFS = 84.0%
2b	Tumor necrosis <90% and margins ≤2 mm; 5-yr LRFS = 76.1%
LRFS = local recurrence-free survival, MSTS = Musculoskeletal Tumor Society
Data from Enneking WF, Spanier SS, Goodman MA: A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980;153:106-120 and Jeys LM, Thorne CJ, Parry M, Gaston CLL, Sumathi VP, Grimer JR: A novel system for the surgical staging of primary high-grade osteosarcoma: The Birmingham classification. Clin Orthop Relat Res 2017;475(3):842-850.

FIGURE 1 Photograph showing a gross en bloc resection specimen of a nonosteogenic bone sarcoma of the humerus.

Assessment

After en bloc tumor resection, evaluation of surgical margins begins in the operating room. Frozen sections (often curettage of bone marrow from remaining bone) can be performed to confirm negative margins or guide additional resection. Permanent pathologic analysis of the specimen is then completed to evaluate final margin status, response to chemotherapy (percentage of tumor necrosis), and other relevant genetic testing (fusion protein, translocation, molecular pathology). For final margin assessment, ink is placed on the periphery of the specimen, and samples are grossly and microscopically evaluated, frequently using the American Joint Committee on Cancer residual tumor classification (the R classification). Margins are classified as R0 (no tumor at ink; negative), R1 (microscopic tumor at ink; positive), and R2 (grossly positive).⁸ Some studies advocate for an additional 1-mm cuff of normal tissue applied to the R classification.⁹^,¹⁰ However, a comparison to an R + 1 mm classification (R1 defined as microscopic tumor within 1 mm of ink) revealed no better prediction of local recurrence with this system.⁷

The resected tumor then undergoes mapping into sections to assist in calculating the overall percentage of necrosis, as a means to determine the response to neoadjuvant chemotherapy. The summative overall percentage of necrosis not only provides prognostic value but can assist in future management strategies.
A review of 293 patients with localized Ewing sarcoma suggested that only patients with 100% necrosis should be considered good responders, because their rates of overall and event-free survival were significantly better than those with any viable tumor in the surgical specimen.¹¹ This was further supported by a 2023 international multicenter analysis of 427 patients, showing that patients who had 100% tumor necrosis had increased overall survival, recurrence-free survival, metastasis-free survival, and event-free survival compared with patients with zero to 99% response.¹² In osteosarcoma, the percentage of necrosis has been shown to be an independent predictor of local recurrence.¹³ In an attempt to reflect the additive or combined effect of margin status and chemotherapy in the surgical staging of osteosarcoma, one study found that the Birmingham Classification was more predictive of local recurrence and overall survival than the Enneking margin definitions alone¹⁴ (Table 1).

PREOPERATIVE PLANNING AND RESECTION BY HISTOLOGY TYPE

Osteosarcoma and Ewing Sarcoma

Osteosarcoma and Ewing sarcoma are the two most common primary bone sarcomas, with a peak incidence in adolescence.¹⁵ Conventional treatment consists of neoadjuvant chemotherapy, wide surgical resection, and adjuvant chemotherapy. Initial imaging studies of the primary tumor at the time of diagnosis, including full bone radiography and MRI, are critical for initial disease staging (size, soft-tissue mass, assessment of skip metastases). Restaging MRI is routinely performed after neoadjuvant chemotherapy to assess the tumor’s gross response to chemotherapy and for surgical planning purposes. Although a reduction in mass size can be seen in both types, substantial reductions in soft-tissue mass size and bone marrow edema extent are more often seen in chemoresponsive Ewing sarcomas. This can undoubtedly lend itself to more numbered and often less morbid surgical resection options.

Although MRI with and without contrast is the benchmark imaging modality for surgical resection planning, there has been ongoing debate regarding the most optimal image sequence to guide bony surgical resection margins. Traditional teaching has suggested that prechemotherapy MRI should be used because it would account for the initial extent of bony edema, theoretically reducing the risk of contaminated margins.¹⁶ Two other studies, however, have shown the strongest correlation and the smallest mean difference between planned radiologic margins and postoperative histologic margins when using postchemotherapy, noncontrast-enhanced T1-weighted images.¹⁷^,¹⁸ In a series of 55 osteosarcomas and Ewing sarcomas, a mean discrepancy of only 5.9 mm between planned radiologic margin and final histologic margin was demonstrated.¹⁷ In a series of 20 Ewing sarcomas, the smallest absolute difference in planned versus postoperative margins was further validated with postchemotherapy T1-weighted images, and it was also noted that adding a minimum of 2 cm to the planned margin limit led to safe histologic margins in all patients.¹⁸

A key point of difference between Ewing sarcoma and all other primary bone sarcomas is the use of radiation therapy for local tumor control. Although osteosarcoma is regarded as a radioresistant disease, local treatment of Ewing sarcoma has been performed with surgical resection, radiation therapy, or both. Direct comparative analyses of radiation alone versus surgery alone are confounded, because there exists inherent bias toward the use of radiation in challenging situations, such as inoperable tumors or during palliative treatment. Nevertheless, there is general agreement that surgery remains a better local control option than radiation alone, as evidenced by improved local control rates¹⁹ and its association with improved survival.²⁰ The use of radiation therapy without surgery should be reserved for inoperable tumors, tumors in difficult sites such as the spine or pelvis, or for palliative purposes. The use of radiation in conjunction with surgery has also become a valid consideration. A comparison of surgery plus radiation versus surgery alone found adjuvant radiation to be particularly useful in reducing local recurrence in large, chemosensitive tumors.²¹ In a 2021 series of 49 pelvic Ewing sarcomas, preoperative radiation was found to have a trend toward better local recurrence-free survival compared with a cohort who selectively had undergone postoperative radiation, thought to be the result of a greater percentage of highly necrotic tumors and negative margins at surgical resection.²²

Chondrosarcoma

Chondrosarcoma is the most common primary bone sarcoma of adulthood. The diagnosis relies heavily on clinical course (progressive pain) and imaging findings, which often consists of endosteal scalloping and cartilage matrix in low-grade tumors and bony destruction and a soft-tissue mass in higher-grade or dedifferentiated tumors. Unlike osteosarcoma and Ewing sarcoma, biopsy may be deferred, because it frequently cannot distinguish low-grade neoplasm from benign cartilage with consistency.²³ The treatment of conventional
central chondrosarcoma is surgical resection alone, being both chemoresistant and radioresistant (exception being the recommended use of chemotherapy in mesenchymal chondrosarcoma, and the potential utility in dedifferentiated chondrosarcoma). Given the low rate of recurrence and metastatic potential of a low-grade chondrosarcoma of the appendicular skeleton, intralesional resection or curettage has demonstrated similar oncologic success compared with wide resection, with the potential to reduce surgical morbidity and improve functional outcomes.²⁴^,²⁵ Nevertheless, wide surgical resection margin is recommended in all other scenarios, because it is associated with improved local recurrence and survival rates.²⁶^,²⁷

SPECIAL CONSIDERATIONS OF PROGNOSIS

Although negative margins are the top priority with localized bone sarcoma in most cases, understanding the sacrificed function and morbidity secondary to obtaining clean margins should always be considered. Two scenarios where function may be considered a higher priority than negative resection margins are (1) localized bone sarcoma in locations with a large amount of critical anatomic structures in proximity, and (2) patients with limited prognosis (metastatic disease or multiple major medical comorbidities precluding an extensive surgery). For nonmetastatic tumors, locations such as the spine, sacrum, pelvis, or shoulder girdle/axilla may create an unacceptable amount of morbidity through the sacrifice of important neurovascular structures during oncologic resection. A thorough knowledge of the tumor histology (low-grade, radiosensitive, etc.) can help guide the decision-making process. Patients with Ewing sarcoma may be treated with definitive radiation when tumors are located in locations such as the pelvis, sacrum, or spine in an effort to spare function. Although prognosis still appears to gain a slight advantage with surgical resection, definitive radiation for Ewing sarcoma remains an acceptable modality of definitive management in select situations and often is more frequently chosen over surgical resection.²⁸ In patients with disseminated metastatic sarcoma disease where prognosis is thought to be limited, or in patients with severe medical comorbidities precluding major surgical intervention, procedures without curative intent (ie, intralesional) can be considered. The clinician should weigh the expected prognosis with the ramifications of intentionally not gaining a negative margin at the local site of resection, such as local recurrence, hardware failure, functional expectations, and pain control. If surgery is offered to this population, pain control and functional preservation for a limited lifespan should be the top priority.

ADVANCED RESECTION TECHNOLOGY

Surgical Navigation

Over the past decade, computer-assisted tumor surgery or surgical navigation has been increasingly used in orthopaedic oncology. Surgical navigation seeks to improve the reproducibility of negative margin resections, and aid in high-precision reconstructions, such as when implanting custom-designed prostheses or performing joint-preserving procedures. Logistically, surgical navigation provides three-dimensional (3D) preoperative planning, intraoperative real-time triplanar image guidance for planned resection osteotomies, and also postoperative validation. In the context of complex pelvic and sacral resections, high rates of successful use, negative margin resection, intraoperative accuracy within 2 mm of planned osteotomy, and low rates of complication related to the technology have been reported.²⁹^,³⁰^,³¹^,³²^,³³ In addition, a comparative study of iliosacral resections demonstrated that navigation assistance yielded fewer positive margins, decreased local recurrence at early follow-up, and shorter surgical time.³⁴ Current evidence remains retrospective and is limited to small cohort sizes.

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