Role of Surgery in Oligometastatic Disease

Primary

Patients

Solitary (%)

Solitary survival (months)

Multiple survival (months)

En Bloc resection (%)

En Bloc survival (months)

Other surg. survival (months)

Breast

307

10.4

35^a

3.9

Prostate

146

5.5

0.7

Kidney

122

19^a

47^a

Lung

^aDenotes a statistically significant difference in survival

The perceived rarity of oligometastatic bone disease is diminished if one considers the vastly greater number of metastatic bone disease patients relative to those with primary bone cancer. Resection surgery is traditionally associated with and reserved for primary bone cancers. The Surveillance, Epidemiology, and End Results (SEER) Program database predicts 3020 (0.9 per 100,000) new primary bone sarcomas of all types for the United States in 2014 [27]. This estimate may even be higher as true population-based data from England identified a stable annual incidence of 0.67–0.81 per 100,000 [28]. Among primary bone cancer patients, some are not candidates for resection due to advanced disease at presentation. In contrast, SEER predicts 816,780 combined new cases of breast, lung, kidney, prostate, and thyroid cancer in 2014 [27]. If only 1 % of these patients have resectable solitary or oligometastatic bone lesions, the number of bone resections for metastatic disease would more than double those of primary bone cancer (Fig. 22.1). The number of patients with resectable bone oligometastases is also likely to grow at a faster rate than those with primary bone sarcomas due to multiple reasons. First, metastatic carcinoma cases will likely continue to increase at a faster rate than primary bone sarcomas. Second, the detection rate of the oligometastatic state may increase with improved diagnostic tests. Finally, advances in treatment (chemotherapy) may render more patients amenable to oligometastatic resection surgery.

Fig. 22.1

Estimated primary bone sarcoma resections compared with estimated resectable oligometastatic bone disease in the United States 2014 (SEER Database)

Indications for Oncologic Surgery for Oligometastases

The term “oncologic resection” generally implies at least local curative intent and typically involves procedures intended to remove or destroy all viable tumor cells; it is used in contrast to the far more common palliative orthopedic procedures intended to ameliorate symptoms without regard to tumor control at the site of intervention. Resection is the classic oncologic intervention and will be the focus of this section; however, other techniques with oncologic intent exist and are described later. High-level evidence supporting oncologic surgery in lieu of less aggressive interventions for bone metastases does not exist. As such, indications for resection are not absolute and should be tailored to patient goals, fitness for surgery, and surgeon experience and judgment. Potential indications for resection of bone metastases are provided in Table 22.2. The primary indication of surgery in the majority of cases is prolongation of survival or even cure. “Expendable” bones for which the morbidity of resection surgery is unlikely to be no worse than fixation or reconstruction constitute another relative indication [29].

Table 22.2

List of relative indications for bone metastasis resection

Indication	Rationale
Solitary or oligometastasis	Render the patient macroscopically disease free; Prolong life, possibly cure
Expendable bones	Morbidity of resection surgery no greater than fixation surgery
Periarticular metastases	Resection may not increase surgical complexity or patient morbidity if arthroplasty is required anyways
Small bones	Surgery other than resection not technically feasible
Highly vascular tumors	Resection may provide better hemostasis than fixation or curettage
Bone metastases with large associated soft tissue masses	Mass effect symptoms often cannot be addressed without resection
Fungating or infected masses	Resection may be required to enable wound healing
Functionless, painful limb	Amputation may be the best palliative option

“Expendable” bones generally not requiring reconstruction:

Sternum (partial).
Scapula (nonarticular).
Clavicle.
Rib.
Spinal elements (if instability is avoided).
Iliac wing.
Pubic rami and symphysis.
Fibula (diaphysis).

Small bones of the hands and feet, although not “expendable,” are often so extensively destroyed by tumor that reconstruction is not feasible. Acral metastases from lung cancer are a classic example of this group [30].

Periarticular metastases of the shoulder and hip are relatively common and are frequently treated with arthroplasty [31]. Often, oncologic resection of these sites may be accomplished with little increased morbidity relative to palliative intralesional arthroplasty. For lesions of the femoral head and neck, there may be no increased morbidity if the abductor insertion to the greater trochanter can be maintained. Less common indications for resection as opposed to stabilization include bone lesions with large, symptomatic soft tissue masses or soft tissue masses impinging upon critical structures such as nerves or vessels. Palliation in such cases is unlikely to be achieved without tumor removal as the mass effect is the source of symptomatology. Finally, palliative amputation is occasionally the best option in advanced cases in which palliative stabilization and limb salvage would leave the patient with greater pain and less function than amputation [32].

Surgical Technique

Resection

The surgical technique required, and specifically the histologic margin necessary to achieve local control of bone metastases, is poorly defined. For the more extensively studied bone sarcomas, substantial debate exists within the orthopedic oncology community regarding the “adequate” surgical margin required. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of primary bone sarcomas recommend wide excision providing histologically negative margins without defining any specific distance from the tumor to the margin [33]. A recent study of osteosarcoma resections found no difference in local recurrence or survival between close (<5 mm) and wide margins [34]. No similar studies are available for bone metastasis. A notable difference relative to osteosarcoma is the increased radiosensitivity of breast, lung, prostate, and thyroid metastases [35]. This increased sensitivity may permit closer margins relative to primary bone sarcomas when postoperative radiotherapy is added to the treatment regimen. Renal cell carcinoma is the potential exception as it is generally considered radioresistant although recent research questions this assumption [36].

Similar to other aspects of metastasectomy, evidence from the hepatic and thoracic surgery literature is more robust with respect to surgical margins. Positive surgical margins have been shown to increase the risk of local recurrence in patients undergoing both liver and pulmonary metastasis resections [37–39]. The residual disease classification (Table 22.3), as opposed to specific margin distances, is typically used for reporting margin status in both the thoracic and hepatobiliary literature [40]. Advantages of this classification include familiarity across disciplines and simplicity; however, all R0 resection may not be equivalent as recent study of liver metastasectomy demonstrated higher local recurrence with resection margin distance of <5 mm [37]. In addition to local disease control at the metastasectomy site, R0 margins have been correlated with improved overall survival for both lung [41] and liver [38] oligometastases. In the absence of bone-specific data, it appears prudent that surgeons pursue R0 resections of bone oligometastases (preferably of >5 mm) based upon the experience with lung and liver resections .

Table 22.3

Residual disease classification of oncologic tumor resections [40]

Type of resection	Pathologic outcome
R0	No tumor at margin
R1	Microscopic tumor at margin
R2	Gross tumor at margin

Extended Curettage

Curettage with the use of adjuvants is now a widely accepted treatment for low-grade chondrosarcoma [42]. Common adjuvants used to extend the zone of tumor necrosis around the curettage cavity include high-speed burring, liquid nitrogen, phenol, hydrogen peroxide, and argon beam coagulation. A combination of modalities such as high-speed burring, liquid nitrogen cryoablation, and hydrogen peroxide irrigation are often utilized. Little evidence exists to support one method in favor of the others and large variations in practice exist based upon surgeon experience, preference, and resource availability [43]. The use of curettage for bone oligometastases is controversial with limited evidence to guide surgeons as to when and how it should be used. Some retrospective studies support the use of curettage as an alternative to resection. A single-institution review of 295 consecutively treated renal cell metastases to bone showed no difference in overall survival or local recurrence comparing en bloc resection and curettage [44]. This equivalence was evident even among patients with solitary metastases. Another retrospective study of solitary pelvic bone metastases compared en bloc resection with extended curettage with the use of adjuvants [45]. No difference in overall survival was identified. The previously referenced cytoreduction literature and the general principles of oligometastases treatment suggest that reduction of tumor burden by curettage when en bloc resection is not feasible may be of benefit. The use of adjuvants to improve local control also seems prudent in light of their known benefits in local control of benign aggressive bone tumors and low-grade chondrosarcoma.

Results of Treatment

Renal cell oligometastasis resections have the largest body of clinical literature (Table 22.4) [6, 24, 26, 44, 46–55]. Reasons for this include the comparatively high rate of renal cell oligometastases [26], radioresistance [36], and until recently the lack of effective chemotherapy [56]. For many years surgical resection was the only intervention available to this cohort. Surgical resection is presently considered standard therapy for oligometastatic renal cell carcinoma as outlined by both NCCN and European Society for Medical Oncology (ESMO) guidelines [57, 58]. An important consideration when considering longer and more extensive resection surgery (relative to stabilization) is patient safety. The acute mortality rate in all of the series collected over a period of three decades was low. Resection may in fact be safer than intramedullary nail fixation with respect to acute cardiopulmonary complications as intramedullary instrumentation is either avoided completely or performed only after tumor removal [59]. Another important factor in determining the overall clinical efficacy of resection versus fixation is durability of the fixation and the potential need for reoperation. Resections typically require more surgical dissection and longer operative times which may predispose to wound complications and infection in an already high-risk population (Fig. 22.2). These risks are counterbalanced by the improved local control and often stouter fixation obtained with resection surgery. A single-institution study of 298 consecutive pathologic proximal femur fractures reported failure rates of 3.1 % for endoprostheses (n = 197), 6.1 % for nails (n = 82), and 42 % for internal fixation (n = 19) (p = 0.03) [60]. Many of the endoprosthesis cases in the study were not resections and therefore are not directly applicable to the present discussion. The previously described SSG study of skeletal metastasis did specifically assess resection cases. SSG reported a lower overall complication rate and lower reoperation rate for resection surgery compared with other interventions for both solitary metastases (10 % vs. 14 %) and multiple metastases (7 % vs. 11 %) [26].

Table 22.4

Results of metastasectomy for renal cell cancer

First author	Pub. year	Total cohort	Resection cases	OS	Notes
Stener [6]	1985	21	21	35.2 months	8 died of unrelated disease; 4 long term survivors (>5year)
Stener [6]	1985	21	21	mean	8 died of unrelated disease; 4 long term survivors (>5year)
Althausen [46]	1997	38	16	NR	55 % 5-year OS for the entire cohort (including non-resection cases)
Kavolius [24]	1998	278^a	5	40 % 5 year	The 141 patients with resection of all macroscopic disease had improved survival relative to those receiving palliative resection or no surgery.
Durr [47]	1999	45	7	NR	15 % 5 year survival of the entire cohort; 28 % 5 year survival for those with solitary metastasis
Baloch [48]	2000	25	25	54 % 3 year	Low complication rate; authors advocated resection for solitary lesions
Baloch [48]	2000	25	25	13 % 5 year
Kollender [49]	2000	45	31	NR	38 % 3 year survival for the entire cohort; 1 local recurrence with resection and 3 local recurrences with curettage
Jung [50]	2003	99	9	80 % 5 year	Wide resection associated with survival advantage on multi-variate analysis
Fuchs [51]	2005	60	13	NR	No survival advantage of wide resection was identified; a lower failure implant failure rate was seen with resection as opposed to fixation
Lin [44]	2007	295	33	38 % 5 year	Solitary metastases but not resections had better survival
Fottner [52]	2010	101	26	~50 % 3 year	Wide resection had statistically better survival; Combined bone and visceral metastasis resections (n = 16) also had survival advantage
Alt [53]	2011	887*	NR	NR	125 patients underwent complete resection of all macroscopic disease which strongly correlated with survival even when 3 or more separate lesions were resected
Evenski [54]	2012	69	NR	42.5 % 5 year	Survival difference was not statistically significant between wide and intralesional resection, but local recurrence was greater with (29 % vs. 5 %) intralesional resection
Hwang [55]	2014	135	135	45 % 3 year	Multivariate analysis demonstrated that multiple skeletal metastases, >1 visceral metastases, and local recurrences did worse
Hwang [55]	2014	135	135	28 % 5 year
Ratasvuori [26]	2014	122	27	47 months	En bloc resection had significantly better survival than other surgical interventions
Ratasvuori [26]	2014	122	27	Median

^a Cohort consists of a mixed group of metastatic renal cell carcinoma patients, not just bone metastases

Fig. 22.2

A 69-year-old male with left shoulder pain and a remote history of scalp melanoma. (a) Radiographs demonstrated a destructive diaphyseal lesion of the proximal humerus. (b) CT-guided biopsy demonstrated clear cell carcinoma versus sarcoma and orthopedic oncology consultation was requested. CT chest/abdomen/pelvis revealed a large right renal mass. (c) MRI better demonstrated the intraosseous extent of the metastasis. Multidisciplinary Fig. 22.2 (continued) tumor board recommended resection of the solitary renal cell metastasis followed by nephrectomy due to the risk of fracture if the primary tumor was treated first. (d) Preoperative embolization images demonstrating elimination of tumor blush after coil placement. (e) Radiographs 6 months after intercalary resection and reconstruction. The patient was treated with 1 year of sunitinib post-nephrectomy and is disease free with excellent left upper extremity function at 2 years post-metastasectomy

Thyroid cancer , specifically the differentiated subtypes, is the second most studied cancer with respect to bone oligometastases resection (Table 22.5) [26, 61–68]. Unlike renal cell carcinoma, radioactive iodine has provided differentiated metastatic thyroid patients an efficacious adjuvant treatment option for several decades. Whereas surgery was initially attempted (first series 1984) for renal cell cancer metastasis due to the lack of other options [6], it was initially (first series 1986) used for thyroid metastases to improve the efficacy of radioactive iodine treatment by reducing the requisite dose [61]. A subsequent French study of 1977 differentiated thyroid cancer patients treated with radioactive iodine from 1958 to 1999 identified complete bone metastasectomy as an independent predictor of survival (p = 0.04) on multivariate analysis [63]. Surgical case series from Vienna, New York, and Houston have all demonstrated improved survival with resection of all macroscopic disease relative to other treatment approaches. Resections of as many as five separate sites have been reported. Figure 22.3 presents an 8-year metastatic thyroid cancer survivor who has undergone five separate resections (2 lung, 1 spine, 1 pelvis, 1 soft tissue) is macroscopically disease free at the time of writing.

Table 22.5

Non-renal bone metastasectomy series

Only gold members can continue reading. Log In or Register to continue