Metastasenchirurgie beim Nierenzellkarzinom

Renal cell carcinomas (RCC) are endowed with impressive metastatic potential. Patients with RCC who present with apparently solitary metastatic lesions represent a small cohort. Due to the different long-term results achieved with surgical resection of metastatic RCC lesions, a generally accepted judgement about this treatment modality is not possible. Several studies suggest that aggressive surgical management can provide an effective treatment, especially in patients with solitary pulmonary metastases. Most noteworthy is the fact that because of the organ distribution of RCC metastases, surgical therapy is dominated by general and thoracic surgeons, neurosurgeons, and orthopaedic surgeons. Therefore, an interdisciplinary approach is one of the most important key points for a successful outcome in these patients.     

Surgical treatment of late metastases of kidney cancer

Whereas 25-57% of patients diagnosed with renal cell carcinoma (RCC) present with metastatic disease, about 50% of (RCC) patients develop metastases after potentially curative radical nephrectomy. Five-year survival at following surgical removal of solitary metastases is approximately 35-50%. Our experience demonstrate that a small cohort of patients benefit from aggressive surgical therapy for consequtively arising solitary distant metastases with long-term palliation.     

Solitary, late metastatic recurrence of renal cell carcinoma: Two extraordinary cases

Late recurrence of renal cell carcinoma (RCC) has been well documented in the literature. We present two extraordinary cases of solitary, late metastatic recurrence of RCC. The first is a case of a solitary, adrenal metastasis excised 38 years after nephrectomy and the second is a case in which two solitary metastatic deposits were resected 14 and 26 years after excision of the primary tumor. In each of these patients the solitary metastases were initially believed to be primary tumors at other sites; however, on histological examination they were found to be metastatic RCC recurrences. In patients with a previous history of RCC presenting with apparently new solitary lesions, metastatic RCC must first be excluded.     

Surgeon's role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: An institutional review

Background: Solitary metastases from a primary renal cell carcinoma (RCC) occur in <10% of patients with metastatic RCC. To date, the benefit of surgically resecting such apparently solitary lesions has not been well documented. Materials and Methods: Forty-one patients (25 men, 16 women) with metastatic renal cell carcinoma treated by surgical excision of solitary metastases (1970–1990) were retrospectively reviewed. They comprised 9% of patients with metastatic hypernephroma seen during this period. All patients had undergone previous curative nephrectomy with a median disease-free interval of 27 months. Patients with skeletal, spinal cord, and lymph node metastases were excluded. Results: Mevtastases were intrathoracic (n=20), intracranial (n=7), and intraabdominal or in the extrapleural chest wall soft tissue (n=10). Three patients had metastases to the thyroid gland and one had a solitary metastasis to an index finger. Median follow-up was 3.2 years. Complete resection was possible in 36 patients (88%) with a single lesion excised in 23 of these 36 patients (64%). There was no operative mortality. Predicted survival from the date of complete resection of metastases was 77%, 59%, and 31% at 1, 3, and 5 years, respectively, with a median survival of 3.4 years. One patient is alive without evidence of recurrent tumor 93 months from the first of 12 complete surgical resections. Varying adjuvant therapy was used in 50% of the patients. An increased histological tumor grade of the metastatic lesion relative to the original RCC was the only significant prognostic indicator identified. Disease-free interval and number of resected lesions were not significantly associated with patient survival. Conclusion: A small fraction of renal cell carcinoma patients are candidates for potentially curative surgical resection of solitary metastatic lesions. Excision of such lesions may contribute to prolonged survival in selected instances. The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Growth rates of primary and metastatic lesions of renal cell carcinoma

BACKGROUND: The natural history and growth rate of renal cell carcinoma (RCC) have not yet been determined. The growth rates of primary lesions in incidentally found RCC were compared with those of metastatic lesions. METHODS: Sixteen patients who did not receive immediate surgical treatment for renal solid masses that were later proven to be RCC were reviewed retrospectively. All primary lesions of the 16 patients were found incidentally. For comparison, metastatic lesions were evaluated in another 16 patients with RCC. Of these, 11 underwent surgical treatment for the primary lesions. RESULTS: The growth rates of primary and metastatic lesions of RCC varied. They ranged from 0.10 to 1.35 cm/year for primary lesions and from 0.08 to 7.87 cm/year for metastatic lesions. The growth rate of primary lesions of incidentally found RCC was lower than that of metastatic lesions (P = 0.0159). The initial tumor diameter and pathological grade did not affect the growth rate of the primary lesion of incidentally found RCC. However, a close correlation was found between the growth rate of metastatic lesions and the pathological grade of the primary lesion in patients with metastasis. CONCLUSIONS: The growth rate of incidentally found RCC varied. Some patients with the disease may be candidates for 'watchful waiting' when an immediate surgical treatment is not indicated, but they should be selected with great caution.     

Contralateral adrenal metastasis of renal cell carcinoma: treatment,outcome and a review

OBJECTIVE: To report the surgical treatment of patients with renal cell carcinoma (RCC) metastatic to the contralateral adrenal gland and compare our experience with previous reports, as such metastases are found in 2.5% of patients with metastatic RCC at autopsy, and the role of resecting metastatic RCC at this site is not well defined. PATIENTS AND METHODS: We retrospectively identified 11 patients who had surgery for metastatic RCC to the contralateral adrenal gland between October 1978 and April 2001. The patients' medical records were reviewed for clinical, surgical and pathological features, and the patients' outcome. RESULTS: The mean (median, range) age of the patients at primary nephrectomy was 60.9 (64, 43-79) years; all had clear cell (conventional) RCC. Synchronous contralateral adrenal metastasis occurred in two patients. The mean (median, range) time to contralateral adrenal metastasis after primary nephrectomy for the remaining nine patients was 5.2 (6.1, 0.8-9.2) years. All patients were treated with adrenalectomy; there were no perioperative complications or mortality. Seven patients died from RCC at a mean (median, range) of 3.9 (3.7, 0.2-10) years after adrenalectomy for contralateral adrenal metastasis; one died from other causes at 3.4 years, one from an unknown cause at 1.7 years and two were still alive at the last follow-up. CONCLUSIONS: The surgical resection of contralateral adrenal metastasis from RCC is safe; although most patients died from RCC, survival may be prolonged in individual patients. Hence, in the era of cytoreductive surgery, the removal of solitary contralateral adrenal metastasis seems to be indicated.     

Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm

OBJECTIVE

To evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise.

PATIENTS AND METHODS

The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy.

RESULTS

Four patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney.

CONCLUSIONS

The introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeutic‐based strategies. This might be a signal for urological surgeons to re‐evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting.     

Renal Cell Carcinoma Metastatic to the Duodenum: Treatment by Classic Pancreaticoduodenectomy and Review of the Literature

Renal cell cancer (RCC) most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain, although metastases can occur elsewhere. RCC metastatic to the duodenum is especially rare, with only a small number of cases reported in the literature. Herein, we describe a case of an 86-year-old woman with a history of RCC treated by radical nephrectomy 13 years previously. The patient presented with duodenal obstruction and anemia from a solitary duodenal mass invading into the pancreas and was treated via classic pancreaticoduodenectomy. Preoperative imaging and intra-operative assessment showed no evidence of other disease. Pathology confirmed metastatic RCC without lymph node involvement. Our case report and review of the English language literature underscore the rarity of this entity and support aggressive surgical treatment in such patients. Presented as a poster at the 41st Annual Meeting of the Pancreas Club, May 20th, 2007, Washington DC.     

Surveillance following radical or partial nephrectomy for renal cell carcinoma

Renal cell carcinoma (RCC) is the most lethal of the common urologic malignancies, with approximately 40% of patients eventually dying of cancer progression. Approximately one third of patients present with metastatic disease and up to 50% treated for localized disease have a recurrence. Although the prognosis generally is poor in these patients, some may respond to immunotherapy and a subset of patients who develop solitary metastases can achieve long-term survival. Therefore, the timely identification of recurrences following surgical extirpation is imperative in the treatment of patients.     

Outcome of hepatic resection for metastatic gastric cancer

The role of hepatic resection for metastatic gastric cancer is less well defined due to the tendency of gastric cancer to widely metastasize. The purpose of this study is to examine the beneficial effect of hepatic resection in patients with metastatic gastric cancer. The clinicopathologic features and long-term results of 11 patients who underwent hepatic resection for metastatic gastric cancer from January 1988 to December 1996 at Seoul National University Hospital were analyzed retrospectively. All resected hepatic metastases were solitary lesions. Among eight patients with synchronous hepatic metastases, one patient with early gastric cancer and lymph node metastases (T1N2M1) remained alive for 8 years 6 months after hepatic resection without recurrence. Among three patients with metachronous hepatic metastases, two patients with advanced gastric cancer and lymph node metastases (T3N2MO, T2N1MO at the initial operation, respectively) survived 8 years 6 months and 3 years after hepatic resection, respectively. Median survival times of synchronous and metachronous hepatic metastases were 13.0 and 74.3 months, respectively. In solitary hepatic metastatic lesions from gastric cancer, surgical resection should be considered as one of the treatment options.     

Extrarenal manifestations of renal cell carcinoma: the primary metastatic lesion (author's transl)]

In 18 patients, histologic evaluation of a solitary distant metastasis with characteristic hypernephroid pattern subsequently led to the diagnosis of renal cell carcinoma. The metastatic lesion was treated surgically in 15 cases; 14 patients underwent radical surgery and one patient with a solitary kidney underwent partial nephrectomy. Osseous metastases were predominant (12 out of 18). There was an excellent morphologic agreement between metastatic and primary lesions: in no case were metastases less differentiated than the primary tumor. Therefore in all cases of metastases with hypernephroid structures an aggressive search for renal malignancy is required. Five-year survival was 5% and identical to a group of 61 patients with metastases and a symptomatic renal cell carcinoma at diagnosis. The poor prognosis was not influenced by surgical extirpation of the solitary metastasis.     

Clinical study of brain metastasis of renal cell carcinoma.

OBJECTIVES: To evaluate the natural history and the efficacy of treatments for renal cell carcinoma (RCC) with brain metastasis, we reviewed 18 patients with this disease. METHODS: Out of 325 cases with RCC treated at Osaka University Hospital from 1957 to 1993, 18 (5.5%, male:female ratio 16:2) cases developed brain metastases. Median follow-up was 44 months after the initial treatment of the primary lesion. Twelve patients had surgical resection of brain metastases (surgical group), and 7 of them received adjuvant radiotherapy. Six patients with poor performance status were treated with supportive therapy alone (nonsurgical group). RESULTS: Of 18 RCC patients with brain metastasis, 16 were male and 2 female. All brain metastases except for 1 case were symptomatic. Median interval between the initial treatment of the primary lesion and the diagnosis of brain metastasis was 19 months. The most frequent metastatic site prior to brain was the lung, which was detected in 7 cases (38.9%). Median survival of the entire group, measured from the onset of brain metastasis, was 9.5 months. One-year survival rate after the diagnosis of brain metastasis was 43.2% (64.8% in surgical group, 0% in nonsurgical group), 3-year 18.5% and 5-year 0%. Among 109 metastatic RCC, 14 patients were treated by lymphokine-activated killer (LAK) therapy. Out of 14 metastatic RCC patients treated by LAK therapy, 3 (21.4%) developed brain metastases. On the other hand, out of 95 metastatic RCC patients without LAK therapy, 15 (15.8%) had brain metastases. There was no significant difference in the rate of brain metastases between these two groups. CONCLUSION: There was a trend for prognosis of the surgical group to be better compared to that of the nonsurgical group, although it is not statistically significant. The optimum treatment for brain metastasis of RCC remains undefined, but our data suggested surgical resection in selected patients might contribute to prolonged survival of patients with brain metastasis. LAK therapy was not necessarily the risk factor of the brain metastasis.     

Surgical treatment of metastases in patients with renal cell carcinoma

Summary The aim of the present study was to investigate the efficacy of surgical excision of metastases in patients with renal cell carcinoma (RCC). Eighteen patients with metastatic RCC underwent resection of metastases between 1988 and 1994 (pulmonary: n = 6; skeletal: n = 6; cerebral: n = 3; local relapse: n = 3). Two patients suffered from synchronous appearance of metastases, whereas in 16 cases a metachronous occurrence was observed. In 12 out of a total of 18 patients metastases were completely resected. These patients survived longer than patients in whom metastases were incompletely resected (30 vs. 12 months). Six out of these 12 patients with a complete resection of metastases are presently free of disease for a mean duration of 24 months (10–34 months). The resection of lung metastases seems to be associated with longer survival times. In conclusion, surgical resection of metastases – solitary or single organ site – especially in the lung appears to be justified in patients with RCC. The surgical excision of skeletal metastases at least improves quality of life.      

Solitary breast mass as initial presentation of clinically silent metastatic renal cell carcinoma

Metastasis to the breast from extramammary tumors is rare. Breast metastases of renal cell carcinoma (RCC) origin have been described in sporadic case reports. We present a patient with a solitary breast mass representing the manifestation of clinically silent, metastatic RCC. A 76-year-old female was 12 years prior removed from radical nephrectomy for localized RCC. Her new breast mass was identified on physical examination. Pathology of the resected mass was diagnostic of metastatic RCC and subsequent imaging studies demonstrated a 1.9 cm renal mass in her solitary kidney. The patient elected subcutaneous Interleukin-2 immunotherapy as primary treatment for her recurrent RCC.     

Surgery for metastases of renal cell carcinoma.

The role of surgery for RCC in the era of emerging effective systemic therapy (usually immunotherapy) is not yet defined except for solitary metastasis. The retrospective analysis of patients subjected to aggressive surgical management after systemic therapy reinforces the need to find better therapeutic modalities in order to achieve complete eradication of metastatic disease. In the meantime, however, we propose these guidelines. First, we would encourage aggressive surgical resection of the clinically solitary metastasis, whether synchronous or metachronous. Continue to follow those patients indefinitely, because relapse is quite likely, but do not give adjuvant systemic therapy unless on protocol. Second, limited metastases in only one organ may behave similarly to a solitary metastasis, and if the metastases are in a site amenable to surgical resection, e.g., lung, initial surgery might be reasonable. Systemic therapy for these patients is highly recommended and need not necessarily wait for recurrence. Third, for patients with multiple metastases, initial systemic therapy followed then by resection of any residual disease in selected patients seems to be supported by the experience at several medical centers. Apparently prolonged survival times have been observed after systemic therapy followed by surgery in highly selected patients, despite finding viable cancer in the overwhelming majority of specimens. One must be mindful of the morbidity of an attempt to remove all known disease, however, and try to weigh this against potential benefit. Only a prospective, randomized trial could ever confirm the value of an aggressive surgical approach to metastatic RCC. In the meantime, however, metastasectomy offers, at the very least, the opportunity to confirm the histologic response to systemic therapy, render some patients disease-free, and possibly promote long-term survival in selected patients.     

Patient survival after surgery for osseous metastases from renal cell carcinoma

BACKGROUND: Skeletal metastases from renal cell carcinoma are highly destructive vascular lesions. They pose unique surgical challenges due to the risk of life-threatening hemorrhage and resistance to other treatments. The goal of this retrospective study was to evaluate factors that may affect survival after surgical treatment of metastases of renal cell carcinoma. METHODS: We performed a retrospective review of a series of 295 consecutive patients who had been treated for metastatic renal cell carcinoma at one institution between 1974 and 2004. There were 226 men and sixty-nine women. A total of 368 metastases of renal cell tumors to the extremities and pelvis were treated. The surgical procedures included curettage with cementing and/or internal fixation (214 tumors), en bloc resection (117), closed nailing (twenty-seven), amputation (four), and other measures (six). Overall survival was calculated with Kaplan-Meier analysis. The log-rank test was used to evaluate the effect of different variables on overall survival. RESULTS: The overall patient survival rates at one and five years were 47% and 11%, respectively. The metastatic pattern had a significant effect on the survival rate (p < 0.0001): patients with a solitary bone metastasis had the most favorable overall survival rate. Patients with multiple bone-only metastases had a better survival rate than patients with pulmonary metastases (p = 0.009). A clear-cell histological subtype was also associated with better survival (p < 0.0001). The tumor grade did not predict survival (p = 0.17). Fifteen patients (5%) died within four weeks after surgery. The causes included acute pulmonary failure (seven patients), multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia (one). There were no deaths attributable to intraoperative hemorrhage. Discussion: Survival beyond twelve months is possible for a substantial proportion of patients with metastatic renal cell carcinoma. Patients with a clear-cell histological subtype, bone-only metastases, and a solitary metastasis have superior survival rates. The presence of pulmonary metastases does not predict early death in a reliable manner, and some patients may survive for years with pulmonary and systemic disease. The data are important for surgeons to consider when choosing treatment for these patients. For example, local control of disease and implant stability are important issues for patients with a potential for a long duration of survival.     

Brain metastases from transitional cell carcinoma of urinary bladder.

Of 293 patients with transitional cell carcinoma of the bladder seen at our institution between April 1977 and December 1987, 9 patients were found to have brain metastasis. Seven of 9 patients were found to have a solitary brain lesion, and in 4 of these, no other site of metastatic disease was identified. Five patients received palliative whole brain irradiation, 3,000 cGy in 10 fractions, due to the presence of multiple lesions of the central nervous system (CNS) or metastases to other sites. The average survival for this group was seven weeks. One patient with a solitary brain metastasis and no other documented metastatic site was hospitalized at another institution, and was managed expectantly receiving only parenteral steroid therapy and survived four weeks. Three patients with solitary lesions and no evidence of other metastatic sites were treated with a combined surgical and radiotherapeutic approach receiving 4,000-5,000 cGy to the lesion site postoperatively. The average survival of that group was twenty-nine months, with one five-year survivor and 1 patient with no evidence of disease fourteen months after treatment. It appears that survival is longer in those patients with solitary lesions, perhaps due, at least in part, to a more aggressive therapeutic approach.     

Differentiating solitary pulmonary metastases in patients with renal cell carcinomas by 18F-fluoro-2-deoxyglucose positron emission tomography--a preliminary report

OBJECTIVE: This preliminary study was to evaluate the characteristics of indeterminate solitary pulmonary lesions in patients with renal cell carcinomas (RCC) using (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). MATERIAL AND METHODS: Fifteen patients with RCC were found to have solitary pulmonary lesions with indeterminate chest X-ray and CT findings. Pulmonary metastases were suspected in all cases so whole body surveys with FDG-PET were performed. RESULTS: FDG-PET correctly identified 9 true-positive and 4 true-negative cases. However, FDG-PET failed to interpret 1 false-positive and 1 false-negative case. Standard uptake values (SUV) were used as parameters to differentiate the solitary pulmonary lesions. Using SUV >2.5 as the cutoff to diagnose malignancy, the sensitivity, specificity, and accuracy of FDG-PET were 90, 80, and 87%, respectively. CONCLUSION: We conclude that FDG-PET is an accurate modality to differentiate solitary pulmonary lesions in patients with RCC.     

The therapeutic value of adrenalectomy in case of solitary metastatic spread originating from primary renal cell cancer

INTRODUCTION: Solitary adrenal metastases occur in about 1.2-10% of renal cell cancer patients. Since the vast majority of intraadrenal lesions can be detected preoperatively, we and others have recently recommended to renounce a routine adrenalectomy during surgery of renal cell cancer. However, the impact of adrenalectomy on the patients' clinical prognosis in case of a solitary metastatic lesion within the adrenal gland remains an issue of controversial discussion. Whereas some authors suggest adrenalectomy as a potentially curative treatment option in these cases, others compare its clinical value with that of a mere lymphadenectomy. PATIENTS AND METHOD: Between 1981 and 2000, 648 patients (440 males and 208 females) underwent nephrectomy in combination with adrenalectomy in our clinic for the diagnosis of renal cell cancer. The median age at first diagnosis was 59 (range 33-84) and 60 (range 20-85) years for male and female patients, respectively. The median postoperative follow - up was 2.4 years (0.2-18 years). According to the TNM - classification system (2003) tumor stages were classified as follows: T1, 228 pat. (37%); T2, 70 pat. (11%); T3, 287 pat. (46%); T4, 37 pat. (6%). In total, 339 patients revealed regional lymph node or distant metastases at the time of the surgical treatment. Although metastases of the adrenal gland were diagnosed in 48 patients, solitary intraadrenal metastases without further systemic spread were observed in only 13 cases. Several patients' and tumor characteristics (age, tumor stage and size, the presence of regional lymph node metastases, the presence of metastatic lesions at different organ sites as well as the detection of solitary intraadrenal metastases) were correlated with the patients' overall survival by univariate and multivariate statistical analysis (logistic Cox regression analysis). RESULTS: The median long - term survival was 4.8 years for the entire cohort of patients investigated. The median long - term survival was 13.8 years and 11.7 years for patients with no evidence of metastatic spread as well as for patients with a solitary intraadrenal metastatic lesion, respectively. Accordingly, the long - term survival rates at 5 and 10 years after surgery were 66%/50% and 51%/51% for patients with no evidence of metastatic spread or isolated intraadrenal metastases. This difference was not statistically significant. In contrast, for patients revealing lymph node or distant metastases at other organ sites, the median long - term survival was significantly decreased (lymph node metastases: 0.7 years; distant metastases: 1.2 years). DISCUSSION: For patients with a solitary intraadrenal metastatic lesion, adrenalectomy is a potentially curative treatment option. The observation that the long - term survival of the latter patients is comparable to that of patients with organ - confined disease might suggest the establishment of a separate TNM - category for patients revealing a solitary metastasis within the adrenal gland and no hint at further systemic metastatic spread.     

Surgical resection of metastatic renal cell carcinoma: The University of Iowa experience

The utility of surgical resection of solitary metastatic sites in renal cell carcinoma remains controversial. Additionally, the small literature detailing the role of surgical management suggests that patients who have surgical resection of metachronous metastases have a better outcome than those presenting synchronously. We reviewed the medical records of all patients with metastatic renal cell carcinoma who underwent nephrectomy at the University of Iowa Hospitals and Clinics between 1980 and 1993. Patients who had undergone surgical resection of metastatic disease, either at presentation or subsequent to their nephrectomy, were identified. Clinical parameters, time to treatment failure, and survival was evaluated. Eighteen patients underwent surgical resection of metastases, 7 were synchronous to their nephrectomy, and 11 developed metachronous metastases. Resected lesions in both groups included metastases to lung, bone, liver, brain, and soft tissue. The median survival of all patients from time of resection to death or last follow-up was 5.7 years (range, 2 days to 10.7+ years). Two patients remain alive, both with recurrent disease at 5.3 and 10.7 years. Mean time from nephrectomy to death was 2.69 years for the synchronous group and 5.97 years for the metachronous group (p = 0.0599). The role of surgical resection in metastatic renal cell carcinoma remains unproven. The survival of this population is significantly longer than that typical for the disease. In our experience there is no difference in time to treatment failure or survival between synchronous and metachronous resection of metastatic disease.