REVIEW URRENT C OPINION
Role of metastasectomy in metastatic renal cell carcinoma Arun Z. Thomas, Mehrad Adibi, Leonardo D. Borregales, Christopher G. Wood, and Jose A. Karam
Purpose of review Management of patients with metastatic renal cell carcinoma is challenging and continues to be delivered in a multidisciplinary context. Even with the advent of systemic targeted therapy, complete remission with these new agents is rare using systemic therapy alone. Surgical resection of the primary tumor and metastatic deposits continues to play an important role in managing patients with metastatic renal cell carcinoma when aiming for complete remissions. To date, despite the lack of level 1 evidence, metastasectomy appears to prolong survival and achieve long-term cure in carefully selected patients. This review examines current evidence for the role of metastasectomy in renal cell carcinoma. Recent findings Studies continue to consistently support a benefit of complete metastasectomy for overall and cancerspecific survival at most sites for resection, with the exception of brain and bone, which tend to perform for symptomatic relief and palliation. Metastasectomy has not yet been examined in a randomized setting. The debate of survival benefit because of selection bias of patients or differences in tumor biology is relevant and has yet to be resolved in the literature. Clearly, careful patient selection remains paramount in optimizing survival benefit from metastasectomy. Summary Patients with isolated surgically resectable metastatic disease, with long disease-free intervals, and with good performance status are likely to benefit the most from metastasectomy. Keywords metastasectomy, metastases, renal cell carcinoma
INTRODUCTION Renal cell carcinoma (RCC) continues to remain an important cause of mortality in the USA, with an estimated 61 560 patients diagnosed with renal tumors in 2015, and 14 080 expected deaths [1]. This represents a 9.8% increase in new diagnoses since 2010 [2]. Of these, 20–30% new cases will have metastatic disease at presentation (synchronous) and up to 40% will develop metachronous metastases after nephrectomy for clinically localized disease [3,4]. Over the last 2 decades, systemic management of metastatic RCC has significantly changed with increased understanding of the molecular biology of RCC. Agents that specifically target relevant biological pathways, such as vascular endothelial growth factor and mammalian target of rapamycin, have revolutionized the treatment of advanced RCC and replaced immunotherapy as first-line therapy [5]. In comparison to immunotherapy, the objective
response in the primary tumor and its associated metastatic deposits with targeted therapy correlate with more modest reductions in tumor size of 20– 30%, as well as improved progression-free survival and overall survival (OS) [6,7]. Complete disease resolution is, however, still extremely rare with these agents alone [8,9]. Hence, surgical resection of the primary tumor and metastatic deposits continue to remain the primary therapeutic intervention for achieving long-term cure in selected
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to Jose A. Karam, MD, FACS Assistant Professor, Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX 77030, USA. Tel: +1 713 792 3250; fax: +1 713 794 4824; e-mail: [email protected] Curr Opin Urol 2015, 25:381–389 DOI:10.1097/MOU.0000000000000196
0963-0643 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
The future of kidney cancer: quo vadis
KEY POINTS Surgical resection of metastatic deposits continues to play an important role in the management of patients with mRCC. In selected patients, metastasectomy prolongs survival and may achieve long-term cure. Metastastectomy also provides palliation in certain patients with advanced mRCC, particularly for brain and bone metastases. Patients with oligometastatic disease, long disease-free interval, good performance status and those amenable to complete surgical resection benefit most from metastasectomy.
patients, even in the targeted therapy era. In this review, we summarize the role of surgical metastasectomy and review surgical considerations for common sites of metastases including lung, bone, liver, retroperitoneum and brain.
METASTASECTOMY Complete versus incomplete/no metastasectomy To date, no randomized controlled trials have compared metastasectomy to medical therapy for patients with metastatic renal cell carcinoma (mRCC). Despite the lack of level 1 evidence, retrospective data suggest that metastasectomy renders cure when performed in selected patients with mRCC. Furthermore, incomplete metastasectomy, although not curative, plays a palliative role in managing patients with mRCC, and still has potential for prolonging survival in some patients. Early studies within the cytokine/immunotherapy era emphasized the role of metastasectomy in patients with mRCC. In a large observational study of 1463 Japanese patients with mRCC, 28% of patients underwent metastasectomy. Improved survival was significantly increased in patients undergoing metastasectomy compared with nonsurgical patients (median 44.3 versus 16.4 months, respectively) [10]. Kavolius et al. examined 278 patients with mRCC of whom 148 underwent a curative metastectomy for their first recurrence, 70 patients underwent noncurative surgery and 67 patients were treated nonsurgically. Five-year OS rates were 44, 14 and 11%, respectively. Among 94 patients with a solitary metastasis, patients with lung metastasis had the most favorable outcomes. Survival rates after curative resection of second and third metastases did not differ from initial 382
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metastasectomy. On multivariate analysis, favorable predictors of survival included a single site of first recurrence, curative resection of first metastasis, a long disease-free interval, a solitary site of first metastasis and a metachronous presentation with recurrence [11]. More recently, Alt et al. [12] reported the survival of patients who underwent complete metastasectomy for multiple RCC metastases in patients undergoing nephrectomy for RCC who developed multiple metastatic lesions. The authors analyzed 887 patients with mRCC, of whom 125 (14%) underwent complete surgical resection of all metastases. After controlling for timing of metastasectomy, location and number of metastases and patient performance status, complete metastasectomy was associated with a significant improvement of median cancer-specific survival (CSS) compared with patients with incomplete or no metastasectomy (4.8 versus 1.3 years, respectively). Patients who had lung-only metastases had a higher 5-year CSS of 73% with complete resection versus 19% without complete resection. A survival advantage from complete metastasectomy was also observed among patients with multiple, nonlung-only metastases, who had a 5-year CSS rate of 32% with complete resection compared with only 12% without complete resection. Complete resection remained predictive of higher CSS for patients who had greater than three metastatic lesions and for patients who had synchronous as well as asynchronous multiple metastases. On multivariate analysis, the absence of complete metastasectomy was associated with a 2.9fold increased risk of death from RCC [12]. A recent analysis from the only systematic review on this topic identified eight studies that assessed metastases from various organs examining complete metastasectomy versus no or incomplete metastasectomy. The majority reported a significantly longer CSS and OS with complete metastasectomy compared with no metastasectomy or incomplete metastasectomy (median of 40.8 versus 14.8 months, respectively). A summary of survival outcome using forest plot hazard ratios for CSS and OS regardless of organ site unequivocally favored complete metastasectomy in all eight studies [13 ]. &&
Integration of systemic therapy and metastasectomy To date, very little evidence exists to assess the role of targeted therapy in conjunction with metastasectomy. This is due to the fact that the majority of studies exist and/or overlap with the immunotherapy era, in which heterogeneity of timing and the type of agents used are difficult to isolate and analyze [12,13 ]. &&
Volume 25 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Role of metastasectomy in metastatic renal cell carcinoma Thomas et al.
In the immunotherapy era, Daliani et al. evaluated 38 patients who underwent metastasectomy after at least 4 months of immunotherapy including IL-2 and INF-a. All patients underwent metastasectomy with curative intent and 90% of patients went on to receive consolidative adjuvant systemic therapy. Almost 80% of patients had stable disease after initial systemic therapy and 21% had a partial or complete response. After surgery 76% of patients had no evidence of disease. Significant predictors of death after metastasectomy were lack of NED and the presence of pulmonary metastases. The median OS for those who had NED was 5.6 years versus 1.4 years for those who did not [14]. Rini et al. [15] described two patients who achieved tumor burden reduction with sunitinib therapy and underwent subsequent metastasectomy with a long-term response. Another study by Thomas et al. examined 19 patients who underwent surgical resection after targeted therapy. Of these, six patients had resection of local recurrence and three patients had distant metastasectomies. They found that this approach was feasible and relatively well tolerated. Major complications occurred in three patients, including death in one because of disseminated intravascular coagulation. Two minor complications were also noted in patients who did not receive postoperative targeted therapy, including a wound seroma and a ventral hernia. At the time of the study, 16 patients were alive at a median follow-up of 8 months, including eight with disease progression. Of the three patients who underwent resection of distant metastases, two were alive at 13 and 16 months [16]. The largest series to date by Karam et al. evaluated the role of metastasectomy in 22 patients with mRCC who received at least one cycle of targeted therapy (pseudo-neoadjuvant therapy) prior to metastasectomy. All patients had surgical resection of all visible disease. Six postoperative complications were observed in four patients including chylous ascities, ileus and atrial fibrillation which all resolved with appropriate management and occurred in patients with retroperitoneal recurrence. At a median follow-up of 109 weeks, 50% of patients were disease free and a further 11 (50%) did not require postoperative targeted therapy. Nine patients required postoperative systemic therapy in which the median time to initiate targeted therapy after metastasectomy was 55 weeks. This study emphasized that treatment with targeted agents followed by consolidative metastasectomy is well tolerated in highly selected patients, resulting in significant time off targeted therapy and long-term tumor-free status [17]. Currently, the role of pseudo-adjuvant therapy is being investigated in 3 randomized prospective clinical trials (using sorafenib, sunitinib, or pazopanib versus
placebo) after complete resection of metastatic disease (clinicaltrials.gov NCT01444807, NCT01216371, and NCT01575548, respectively).
Risk stratification At the time of disease progression (local and or systemic), deciding between observation, medical and or surgical therapy can pose a significant dilemma for clinicians because of the significant heterogeneity that exists within the literature. As already highlighted, no level 1 evidence exists and significant bias can be attributed to the majority of published retrospective series on metastasectomy in RCC. Furthermore, future prospects of successfully completing a prospective randomized trial within this particular patient population are highly unlikely. Despite such challenges, it is clear from the literature that there are a proportion of patients that benefit from aggressive surgical resection of metastatic deposits not only for palliation, but also those who achieve long-term remission or cure. Traditionally, the most widely used model in metastatic RCC is the Memorial Sloan Kettering Cancer Center (MSKCC) risk grouping. This model utilizes LDH, corrected calcium, serum hemoglobin, Karnofsky performance status and time from diagnosis to start of therapy to risk stratify patients for survival [18]. Even though the MSKCC risk groups were formulated to stratify survival in patients with mRCC who would most benefit from cytoreductive nephrectomy, these same predictors have been applied in patients undergoing metastasectomy after prior nephrectomy [19]. Eggener et al. evaluated 129 patients disease recurrence following surgery for RCC. Using the MSKCC risk grouping, a five-point prognostic scoring system for patients with advanced RCC was applied classifying patients into favorable, intermediate and poor risk categories. Median, 2 and 5-year survival rates were shown to strongly correlate with risk category (favorable: 73 months, 81%, 57%; intermediate: 28 months, 54%, 16%; poor: 6 months, 11%, 0%, respectively). Patients designated as favorable risk were more likely to undergo metastasectomy highlighting the variability of patient selection. On multivariate analysis, those not undergoing metastasectomy and of higher risk category were both independently associated with decreased survival [20]. In the targeted therapy era, Heng et al. retrospectively reviewed 645 patients with metastatic RCC treated with targeted therapy. They identified six predictors of survival similar to the MSKCC criteria including hemoglobin below lower limit of normal (LLN), calcium above upper limit of normal (ULN), Karnofsky score 80% or less and systemic disease within 1 year of diagnosis as independent
0963-0643 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-urology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
383
The future of kidney cancer: quo vadis
predictors of decreased survival. Absolute neutrophil count greater than ULN and platelets greater than ULN were also independent adverse prognostic factors. Based on these six prognostic factors, patients were risk stratified to favorable (zero adverse factors: 75% 2-year survival), intermediate (one to two adverse factors: 53% 2-year survival) or poor (three to six adverse factors: 7% survival) [21]. Both the MSKCC and Heng criteria (also known as IMDC, International Metastatic RCC Database Consortium) are potentially useful to risk stratify patient being considered for metastasectomy, in addition to their use for choice of first-line systemic therapy.
METASTASECTOMY BY LOCATION/ ORGAN SITE Lung metastasis Table 1 lists the most common metastatic sites from RCC. The lung is the most common site of
metastatic spread of advanced RCC with an incidence ranging from 45 to 75% [22]. The resection of solitary lung metastasis dates as far back as 1939 suggesting the potential for long-term cure in select patients [23]. Since then, surgery with wedge resection, segmentectomy, lobectomy or pneumonectomy continues to remain the only effective treatment for patients with isolated lung metastases with 5-year survival rates ranging from 36 to 50% [24]. A large study by Pfannschmidt and colleagues identified 149 out of 191 patients who had complete resection after surgical excision for pulmonary metastases. Similar to preceding studies, the 5-year survival rate after complete metastasectomy versus incomplete resection was 41.5 and 22.1%, respectively. Multivariate analyses showed that the number of pulmonary metastases (
Role of metastasectomy in metastatic renal cell carcinoma Arun Z. Thomas, Mehrad Adibi, Leonardo D. Borregales, Christopher G. Wood, and Jose A. Karam
Purpose of review Management of patients with metastatic renal cell carcinoma is challenging and continues to be delivered in a multidisciplinary context. Even with the advent of systemic targeted therapy, complete remission with these new agents is rare using systemic therapy alone. Surgical resection of the primary tumor and metastatic deposits continues to play an important role in managing patients with metastatic renal cell carcinoma when aiming for complete remissions. To date, despite the lack of level 1 evidence, metastasectomy appears to prolong survival and achieve long-term cure in carefully selected patients. This review examines current evidence for the role of metastasectomy in renal cell carcinoma. Recent findings Studies continue to consistently support a benefit of complete metastasectomy for overall and cancerspecific survival at most sites for resection, with the exception of brain and bone, which tend to perform for symptomatic relief and palliation. Metastasectomy has not yet been examined in a randomized setting. The debate of survival benefit because of selection bias of patients or differences in tumor biology is relevant and has yet to be resolved in the literature. Clearly, careful patient selection remains paramount in optimizing survival benefit from metastasectomy. Summary Patients with isolated surgically resectable metastatic disease, with long disease-free intervals, and with good performance status are likely to benefit the most from metastasectomy. Keywords metastasectomy, metastases, renal cell carcinoma
INTRODUCTION Renal cell carcinoma (RCC) continues to remain an important cause of mortality in the USA, with an estimated 61 560 patients diagnosed with renal tumors in 2015, and 14 080 expected deaths [1]. This represents a 9.8% increase in new diagnoses since 2010 [2]. Of these, 20–30% new cases will have metastatic disease at presentation (synchronous) and up to 40% will develop metachronous metastases after nephrectomy for clinically localized disease [3,4]. Over the last 2 decades, systemic management of metastatic RCC has significantly changed with increased understanding of the molecular biology of RCC. Agents that specifically target relevant biological pathways, such as vascular endothelial growth factor and mammalian target of rapamycin, have revolutionized the treatment of advanced RCC and replaced immunotherapy as first-line therapy [5]. In comparison to immunotherapy, the objective
response in the primary tumor and its associated metastatic deposits with targeted therapy correlate with more modest reductions in tumor size of 20– 30%, as well as improved progression-free survival and overall survival (OS) [6,7]. Complete disease resolution is, however, still extremely rare with these agents alone [8,9]. Hence, surgical resection of the primary tumor and metastatic deposits continue to remain the primary therapeutic intervention for achieving long-term cure in selected
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to Jose A. Karam, MD, FACS Assistant Professor, Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX 77030, USA. Tel: +1 713 792 3250; fax: +1 713 794 4824; e-mail: [email protected] Curr Opin Urol 2015, 25:381–389 DOI:10.1097/MOU.0000000000000196
0963-0643 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-urology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
The future of kidney cancer: quo vadis
KEY POINTS Surgical resection of metastatic deposits continues to play an important role in the management of patients with mRCC. In selected patients, metastasectomy prolongs survival and may achieve long-term cure. Metastastectomy also provides palliation in certain patients with advanced mRCC, particularly for brain and bone metastases. Patients with oligometastatic disease, long disease-free interval, good performance status and those amenable to complete surgical resection benefit most from metastasectomy.
patients, even in the targeted therapy era. In this review, we summarize the role of surgical metastasectomy and review surgical considerations for common sites of metastases including lung, bone, liver, retroperitoneum and brain.
METASTASECTOMY Complete versus incomplete/no metastasectomy To date, no randomized controlled trials have compared metastasectomy to medical therapy for patients with metastatic renal cell carcinoma (mRCC). Despite the lack of level 1 evidence, retrospective data suggest that metastasectomy renders cure when performed in selected patients with mRCC. Furthermore, incomplete metastasectomy, although not curative, plays a palliative role in managing patients with mRCC, and still has potential for prolonging survival in some patients. Early studies within the cytokine/immunotherapy era emphasized the role of metastasectomy in patients with mRCC. In a large observational study of 1463 Japanese patients with mRCC, 28% of patients underwent metastasectomy. Improved survival was significantly increased in patients undergoing metastasectomy compared with nonsurgical patients (median 44.3 versus 16.4 months, respectively) [10]. Kavolius et al. examined 278 patients with mRCC of whom 148 underwent a curative metastectomy for their first recurrence, 70 patients underwent noncurative surgery and 67 patients were treated nonsurgically. Five-year OS rates were 44, 14 and 11%, respectively. Among 94 patients with a solitary metastasis, patients with lung metastasis had the most favorable outcomes. Survival rates after curative resection of second and third metastases did not differ from initial 382
www.co-urology.com
metastasectomy. On multivariate analysis, favorable predictors of survival included a single site of first recurrence, curative resection of first metastasis, a long disease-free interval, a solitary site of first metastasis and a metachronous presentation with recurrence [11]. More recently, Alt et al. [12] reported the survival of patients who underwent complete metastasectomy for multiple RCC metastases in patients undergoing nephrectomy for RCC who developed multiple metastatic lesions. The authors analyzed 887 patients with mRCC, of whom 125 (14%) underwent complete surgical resection of all metastases. After controlling for timing of metastasectomy, location and number of metastases and patient performance status, complete metastasectomy was associated with a significant improvement of median cancer-specific survival (CSS) compared with patients with incomplete or no metastasectomy (4.8 versus 1.3 years, respectively). Patients who had lung-only metastases had a higher 5-year CSS of 73% with complete resection versus 19% without complete resection. A survival advantage from complete metastasectomy was also observed among patients with multiple, nonlung-only metastases, who had a 5-year CSS rate of 32% with complete resection compared with only 12% without complete resection. Complete resection remained predictive of higher CSS for patients who had greater than three metastatic lesions and for patients who had synchronous as well as asynchronous multiple metastases. On multivariate analysis, the absence of complete metastasectomy was associated with a 2.9fold increased risk of death from RCC [12]. A recent analysis from the only systematic review on this topic identified eight studies that assessed metastases from various organs examining complete metastasectomy versus no or incomplete metastasectomy. The majority reported a significantly longer CSS and OS with complete metastasectomy compared with no metastasectomy or incomplete metastasectomy (median of 40.8 versus 14.8 months, respectively). A summary of survival outcome using forest plot hazard ratios for CSS and OS regardless of organ site unequivocally favored complete metastasectomy in all eight studies [13 ]. &&
Integration of systemic therapy and metastasectomy To date, very little evidence exists to assess the role of targeted therapy in conjunction with metastasectomy. This is due to the fact that the majority of studies exist and/or overlap with the immunotherapy era, in which heterogeneity of timing and the type of agents used are difficult to isolate and analyze [12,13 ]. &&
Volume 25 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Role of metastasectomy in metastatic renal cell carcinoma Thomas et al.
In the immunotherapy era, Daliani et al. evaluated 38 patients who underwent metastasectomy after at least 4 months of immunotherapy including IL-2 and INF-a. All patients underwent metastasectomy with curative intent and 90% of patients went on to receive consolidative adjuvant systemic therapy. Almost 80% of patients had stable disease after initial systemic therapy and 21% had a partial or complete response. After surgery 76% of patients had no evidence of disease. Significant predictors of death after metastasectomy were lack of NED and the presence of pulmonary metastases. The median OS for those who had NED was 5.6 years versus 1.4 years for those who did not [14]. Rini et al. [15] described two patients who achieved tumor burden reduction with sunitinib therapy and underwent subsequent metastasectomy with a long-term response. Another study by Thomas et al. examined 19 patients who underwent surgical resection after targeted therapy. Of these, six patients had resection of local recurrence and three patients had distant metastasectomies. They found that this approach was feasible and relatively well tolerated. Major complications occurred in three patients, including death in one because of disseminated intravascular coagulation. Two minor complications were also noted in patients who did not receive postoperative targeted therapy, including a wound seroma and a ventral hernia. At the time of the study, 16 patients were alive at a median follow-up of 8 months, including eight with disease progression. Of the three patients who underwent resection of distant metastases, two were alive at 13 and 16 months [16]. The largest series to date by Karam et al. evaluated the role of metastasectomy in 22 patients with mRCC who received at least one cycle of targeted therapy (pseudo-neoadjuvant therapy) prior to metastasectomy. All patients had surgical resection of all visible disease. Six postoperative complications were observed in four patients including chylous ascities, ileus and atrial fibrillation which all resolved with appropriate management and occurred in patients with retroperitoneal recurrence. At a median follow-up of 109 weeks, 50% of patients were disease free and a further 11 (50%) did not require postoperative targeted therapy. Nine patients required postoperative systemic therapy in which the median time to initiate targeted therapy after metastasectomy was 55 weeks. This study emphasized that treatment with targeted agents followed by consolidative metastasectomy is well tolerated in highly selected patients, resulting in significant time off targeted therapy and long-term tumor-free status [17]. Currently, the role of pseudo-adjuvant therapy is being investigated in 3 randomized prospective clinical trials (using sorafenib, sunitinib, or pazopanib versus
placebo) after complete resection of metastatic disease (clinicaltrials.gov NCT01444807, NCT01216371, and NCT01575548, respectively).
Risk stratification At the time of disease progression (local and or systemic), deciding between observation, medical and or surgical therapy can pose a significant dilemma for clinicians because of the significant heterogeneity that exists within the literature. As already highlighted, no level 1 evidence exists and significant bias can be attributed to the majority of published retrospective series on metastasectomy in RCC. Furthermore, future prospects of successfully completing a prospective randomized trial within this particular patient population are highly unlikely. Despite such challenges, it is clear from the literature that there are a proportion of patients that benefit from aggressive surgical resection of metastatic deposits not only for palliation, but also those who achieve long-term remission or cure. Traditionally, the most widely used model in metastatic RCC is the Memorial Sloan Kettering Cancer Center (MSKCC) risk grouping. This model utilizes LDH, corrected calcium, serum hemoglobin, Karnofsky performance status and time from diagnosis to start of therapy to risk stratify patients for survival [18]. Even though the MSKCC risk groups were formulated to stratify survival in patients with mRCC who would most benefit from cytoreductive nephrectomy, these same predictors have been applied in patients undergoing metastasectomy after prior nephrectomy [19]. Eggener et al. evaluated 129 patients disease recurrence following surgery for RCC. Using the MSKCC risk grouping, a five-point prognostic scoring system for patients with advanced RCC was applied classifying patients into favorable, intermediate and poor risk categories. Median, 2 and 5-year survival rates were shown to strongly correlate with risk category (favorable: 73 months, 81%, 57%; intermediate: 28 months, 54%, 16%; poor: 6 months, 11%, 0%, respectively). Patients designated as favorable risk were more likely to undergo metastasectomy highlighting the variability of patient selection. On multivariate analysis, those not undergoing metastasectomy and of higher risk category were both independently associated with decreased survival [20]. In the targeted therapy era, Heng et al. retrospectively reviewed 645 patients with metastatic RCC treated with targeted therapy. They identified six predictors of survival similar to the MSKCC criteria including hemoglobin below lower limit of normal (LLN), calcium above upper limit of normal (ULN), Karnofsky score 80% or less and systemic disease within 1 year of diagnosis as independent
0963-0643 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-urology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
383
The future of kidney cancer: quo vadis
predictors of decreased survival. Absolute neutrophil count greater than ULN and platelets greater than ULN were also independent adverse prognostic factors. Based on these six prognostic factors, patients were risk stratified to favorable (zero adverse factors: 75% 2-year survival), intermediate (one to two adverse factors: 53% 2-year survival) or poor (three to six adverse factors: 7% survival) [21]. Both the MSKCC and Heng criteria (also known as IMDC, International Metastatic RCC Database Consortium) are potentially useful to risk stratify patient being considered for metastasectomy, in addition to their use for choice of first-line systemic therapy.
METASTASECTOMY BY LOCATION/ ORGAN SITE Lung metastasis Table 1 lists the most common metastatic sites from RCC. The lung is the most common site of
metastatic spread of advanced RCC with an incidence ranging from 45 to 75% [22]. The resection of solitary lung metastasis dates as far back as 1939 suggesting the potential for long-term cure in select patients [23]. Since then, surgery with wedge resection, segmentectomy, lobectomy or pneumonectomy continues to remain the only effective treatment for patients with isolated lung metastases with 5-year survival rates ranging from 36 to 50% [24]. A large study by Pfannschmidt and colleagues identified 149 out of 191 patients who had complete resection after surgical excision for pulmonary metastases. Similar to preceding studies, the 5-year survival rate after complete metastasectomy versus incomplete resection was 41.5 and 22.1%, respectively. Multivariate analyses showed that the number of pulmonary metastases (
