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THE ROLE OF METASTASECTOMY IN THE MANAGEMENT OF RENAL CANCER
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794
THE ROLE OF METASTASECTOMY IN THE MANAGEMENT OF RENAL CANCER
THE ROLE OF METASTASECTOMY IN RENAL CELL CARCINOMA
Ramsey S., Aitchison M.
University Hospital Leuven, Urology, Leuven, Belgium
Gartnavel General Hospital, Urology, Glasgow, United Kingdom INTRODUCTION & OBJECTIVES: Surgical resection of RCC provides patients with the best chance of meaningful survival. The prognosis of metastatic RCC is poor, with a median survival of 9 months. Solitary distant metastases are said to occur in less than 2.5% of cases (O’Dea et al. J Urol 1978;120:540-2) but surgical resection or metastasectomy can significantly improve life expectancy.
INTRODUCTION & OBJECTIVES: More than 60% of patients diagnosed with renal cell carcinoma (RCC) have synchronous or metachronous metastases in the course of their disease. In the absence of effective non-surgical therapy, surgical management in selected patients with metastatic RCC should be considered. The selection criteria for patients to undergo aggressive surgical management are not well defined. The current study aimed to determine predictive factors for long-term survival after metastasectomy.
MATERIAL & METHODS: A retrospective analysis of 711 referrals to our regional referral centre using a computer based prospective database was carried out. This specialist service has been run for 7 years by a lead oncologist and urologist, with an attached cardiothoracic and general surgeon. 31 patients were identified who underwent resection of solitary distant metastases, and had at least 6 months follow-up subsequent to this. This represents 4% of total caseload.
MATERIAL & METHODS: We retrospectively reviewed the records of 59 patients who underwent one or multiple metastasectomies for metastatic RCC between 1984 and 2003. The population included 37 male and 22 female patients. Clinical and pathologic data were reviewed in order to determine whether outcome after metastasectomy was affected by the age of the patient, the site of metastasis, disease free interval (DFI) from nephrectomy to the diagnosis of metastasis, tumour-stage, or history of prior metastasectomy.
RESULTS: 20 men and 11 women were identified. 6 patients had metastatic disease at presentation, the remaining 25 patients developed metastatic disease following a potentially curative nephrectomy. The median time from nephrectomy to metastasectomy was 36 months (range 2-274.) The most common site for metastasectomy was pulmonary (n=16) followed by 5 bony lesions, 3 contralateral adrenal, 3 cerebral, 2 hepatic, 1 thyroid and 1 soft tissue. Following metastasectomy, 10 patients (32%) have remained disease-free whilst 21 patients have developed further metastatic disease, median 18 months post-metastasectomy (4-101 months). Only 3 patients with recurrent metastatic disease were suitable for further metastasectomy. of these, 2 patients remain disease free, and 1 has stable metastatic disease at 81, 147 and 90 months post-nephrectomy respectively. 15 patients (48%) are deceased, all due to metastatic disease. However, overall median survival following metastasectomy was 26 months (5 – 147) which demonstrates a survival benefit when compared to results from historical series. CONCLUSIONS: Metastasectomy requires a multidisciplinary approach, and in patients with solitary distant metastases, surgical resection can increase overall survival. Recurrence rates are relatively high, though a few patients will be suitable for further surgery. The introduction of small molecule inhibitors may improve outcomes for RCC patients, but until these are widespread, surgery for metastatic disease in a specialist centre should remain an option.
795 HOW SHOULD WE MANAGE PATIENTS WITH T4 RENAL TUMOURS? Ramsey S., Aitchison M. Gartnavel General Hospital, Urology, Glasgow, United Kingdom INTRODUCTION & OBJECTIVES: Despite an increase in serendipitously detected tumours, all stages of RCC are increasing in incidence. (Chow et al. JAMA 1999;281:162831) The best chance of cure for patients with localised disease is radical surgery and a survival benefit exists for patients undergoing cytoreductive nephrectomy. T4 tumours have invaded beyond Gerota’s fascia, possibly into adjacent organs. They are rare, with little published evidence evaluating the effectiveness of radical surgery in T4 disease. MATERIAL & METHODS: Our tertiary referral centre for RCC has maintained a prospectively collected computer database since commencement in 1997. This database of 711 patients was used to identify 31 patients (4%) with T4 renal tumours. RESULTS: The patients were aged between 45 and 78, mean age 66 years. 65% were male, and 11 had distant metastases at presentation. 29 patients had details of their presentation recorded. Only 17% had incidentally detected tumours, whilst 45% had local symptoms such as loin pain, haematuria, and 38% had systemic symptoms such as weight loss or anaemia. 11 patients underwent potentially curative resections of their primary. 3 patients were referred after failed resection in a non-specialist hospital. 5 patients underwent a cytoreductive nephrectomy. 12 patients were unfit for surgery (7 with localised tumour, 5 with metastatic disease) due to poor performance status, or extensive co-morbidity. No patient underwent neoadjuvant immunotherapy. Within the curative resection group, 82% had Grade 4 tumours, and over 50% had evidence of sarcomatoid differentiation. The adjacent organ involved was most commonly psoas, followed by colon, spleen and diaphragm. The median survival in patients unfit for surgery was 7 months (range 1-18). There was a significant survival advantage for patients who underwent surgical resection of primary tumour, median 17 months, (5 – 65 months). (p=0.002 Mann-Whitney) The median survival in patients who underwent a cytoreductive nephrectomy was 27 months, (3 to 56). There was no survival advantage for patients with incidentally detected tumours when compared with symptomatic presentation. (p=0.356 Mann-Whitney). There was no difference in survival between patients with localised or metastatic disease at presentation, (p=0.836 Mann-Whitney) confirming the staging of T4 disease as Stage IV, independent of distant metastases. CONCLUSIONS: T4 tumours present a unique challenge for the surgical oncologist. Surgical resection in selected patients with good performance status can lead to a significant survival benefit for some. Due to the small numbers of T4 tumours annually and technical difficulty of complete resection these patients should be referred to a specialist renal cancer centre. UKwide collaboration is required to assess the role for neoadjuvant immunotherapy.
Ghysel C., Joniau S., Van Poppel H.
RESULTS: The population consisted of 59 patients. In all patients, primary nephrectomy was performed. Synchronous metastases were found in 16 cases and metachronous metastases in 43 cases. Overall, 74 metastasectomies with curative intent were performed: 46 patients underwent a single metastasectomy, 11 and 2 patients had metastases resected 2 and 3 times respectively. The median age at first metastasectomy was 60 years (range 2579). Metastasectomies were performed at different locations: lung n=14, adrenal n=14, bone n=12, bowel n=9, liver n=7, retroperitoneum n=5, thyroid n=4, contralateral kidney n=3, bladder n=2, other n=8. Minor complications occurred in 14 patients, major complications in 2 and 2 lethal complications occurred shortly after metastasectomy (cardiac arrest, pulmonary embolism). 5-year overall survival was 58%. Univariate Cox regression analysis identified location of metastases at the lung, DFI >2years, initial tumour stage T1 and age at first metastasectomy <60 years as significant predictors for better disease-specific survival. At multivariate Cox regression analysis, only location of metastases at the lung and the age at first metastasectomy <60 years were independently correlated with better disease-specific survival. Overall survival in repeated metastasectomy was equal to single metastasectomy. CONCLUSIONS: In a selected patient group, metastasectomy with curative intent can provide an overall 5-year survival of 58%. Age younger than 60 and location of metastases in the lung are related with an even longer survival.
P48 NEURO-UROLOGY: SENSORY MECHANISMS Friday, 7 April, 12.15-13.45, Room 242 / Level 2 796 THE ESSENCE OF URGENCY: VANILLOID RECEPTOR EXPRESSION IN WOMEN’S BLADDERS Millard R.J.1, Liu L.2, Kristiana I.2, Mansfield K.J.2, Vaux K.3, Burcher E.2 1
Prince of Wales Hospital, Urology, Sydney, Australia, 2University of New South Wales, Physiology & Pharmacology, Sydney, Australia, 3Sydney Adventist Hospital, Urology, Sydney, Australia INTRODUCTION & OBJECTIVES: Female patients with “sensory urgency” (SU): the symptom complex of urgency associated with pain, burning or discomfort, often associated with frequency and nocturia, are difficult to treat. Vanilloid receptors (TRPV1) on afferent neurons and on urothelium may participate in signalling from the bladder. Our aim was to examine whether changes in TRPV1 expression occur in bladder from SU patients compared with controls and with patients with idiopathic detrusor overactivity (IDO).
MATERIAL & METHODS: Biopsies from body and trigone were obtained from patients with SU (female, aged 21-82) who had undergone videourodynamics to exclude detrusor overactivity and define the volume at first bladder sensation. Women with recurrent proven infection were excluded. Asymptomatic age-matched females with prior history of carcinoma acted as controls. A similar cohort of women with IDO were also evaluated. Biopsies were collected into “RNALater”. Specimens were dissected into two layers, mucosa and detrusor muscle, before RNA extraction and quantitative competitive (QC) RT-PCR (Mansfield et al 2005 Br J Pharmacol 144: 1089-1099). RESULTS: In control biopsies, TRPV1 mRNA was present in greater density in mucosa than in detrusor muscle (15.3 x 105 cf. 4.6 x 105 copies/μg RNA, both n=15, P<0.01). In SU patients, TRPV1 mRNA expression was significantly higher in trigonal mucosa than in body mucosa (Table 1). There was no significant change in TRPV1 expression in body mucosa from SU specimens compared with matched controls. In SU patients, the level of TRPV1 expression in trigonal mucosa (but not body mucosa) was significantly inversely correlated (r2=0.41, P<0.01) with the volume at first bladder sensation on urodynamic testing (Fig 1A). The women with IDO showed no changes in TRPV1 expression compared with controls (Table 1) and no relation to urodynamic parameters (Fig 1B, r2=0.10, P=0.3). Table 1. The amount of TRPV1 mRNA (Median (IQR), copies x 105/μg total RNA) expressed in human bladder biopsies, determined by QC-RT-PCR. Bladder region Body mucosa
Trigonal mucosa
Control
13.8 (6.34-20.7) n = 41
N.A.
P value
SU
7.79 (4.22-20.3) n = 18
19.3 (10.6-31.7) n = 22
P < 0.01
IDO
13.7 (3.94-18.5) n = 10
11.6 (8.49-17.7) n = 13
P > 0.05
Patient group
N.A., specimens not available for ethical reasons.
CONCLUSIONS: We hypothesise that excessive afferent signalling via TRPV1 receptors in the trigone region may be related to an early first bladder sensation and sensory urgency. By contrast, the IDO bladders with symptoms of “urgency for fear of leakage” (formerly, motor urgency) have no increase in TRPV1 receptor mRNA expression. This suggests that two types of urgency exist, that they are modulated via different receptors, and that “sensory urgency” should be restored to the urological lexicon.
Eur Urol Suppl 2006;5(2):221
794
THE ROLE OF METASTASECTOMY IN THE MANAGEMENT OF RENAL CANCER
THE ROLE OF METASTASECTOMY IN RENAL CELL CARCINOMA
Ramsey S., Aitchison M.
University Hospital Leuven, Urology, Leuven, Belgium
Gartnavel General Hospital, Urology, Glasgow, United Kingdom INTRODUCTION & OBJECTIVES: Surgical resection of RCC provides patients with the best chance of meaningful survival. The prognosis of metastatic RCC is poor, with a median survival of 9 months. Solitary distant metastases are said to occur in less than 2.5% of cases (O’Dea et al. J Urol 1978;120:540-2) but surgical resection or metastasectomy can significantly improve life expectancy.
INTRODUCTION & OBJECTIVES: More than 60% of patients diagnosed with renal cell carcinoma (RCC) have synchronous or metachronous metastases in the course of their disease. In the absence of effective non-surgical therapy, surgical management in selected patients with metastatic RCC should be considered. The selection criteria for patients to undergo aggressive surgical management are not well defined. The current study aimed to determine predictive factors for long-term survival after metastasectomy.
MATERIAL & METHODS: A retrospective analysis of 711 referrals to our regional referral centre using a computer based prospective database was carried out. This specialist service has been run for 7 years by a lead oncologist and urologist, with an attached cardiothoracic and general surgeon. 31 patients were identified who underwent resection of solitary distant metastases, and had at least 6 months follow-up subsequent to this. This represents 4% of total caseload.
MATERIAL & METHODS: We retrospectively reviewed the records of 59 patients who underwent one or multiple metastasectomies for metastatic RCC between 1984 and 2003. The population included 37 male and 22 female patients. Clinical and pathologic data were reviewed in order to determine whether outcome after metastasectomy was affected by the age of the patient, the site of metastasis, disease free interval (DFI) from nephrectomy to the diagnosis of metastasis, tumour-stage, or history of prior metastasectomy.
RESULTS: 20 men and 11 women were identified. 6 patients had metastatic disease at presentation, the remaining 25 patients developed metastatic disease following a potentially curative nephrectomy. The median time from nephrectomy to metastasectomy was 36 months (range 2-274.) The most common site for metastasectomy was pulmonary (n=16) followed by 5 bony lesions, 3 contralateral adrenal, 3 cerebral, 2 hepatic, 1 thyroid and 1 soft tissue. Following metastasectomy, 10 patients (32%) have remained disease-free whilst 21 patients have developed further metastatic disease, median 18 months post-metastasectomy (4-101 months). Only 3 patients with recurrent metastatic disease were suitable for further metastasectomy. of these, 2 patients remain disease free, and 1 has stable metastatic disease at 81, 147 and 90 months post-nephrectomy respectively. 15 patients (48%) are deceased, all due to metastatic disease. However, overall median survival following metastasectomy was 26 months (5 – 147) which demonstrates a survival benefit when compared to results from historical series. CONCLUSIONS: Metastasectomy requires a multidisciplinary approach, and in patients with solitary distant metastases, surgical resection can increase overall survival. Recurrence rates are relatively high, though a few patients will be suitable for further surgery. The introduction of small molecule inhibitors may improve outcomes for RCC patients, but until these are widespread, surgery for metastatic disease in a specialist centre should remain an option.
795 HOW SHOULD WE MANAGE PATIENTS WITH T4 RENAL TUMOURS? Ramsey S., Aitchison M. Gartnavel General Hospital, Urology, Glasgow, United Kingdom INTRODUCTION & OBJECTIVES: Despite an increase in serendipitously detected tumours, all stages of RCC are increasing in incidence. (Chow et al. JAMA 1999;281:162831) The best chance of cure for patients with localised disease is radical surgery and a survival benefit exists for patients undergoing cytoreductive nephrectomy. T4 tumours have invaded beyond Gerota’s fascia, possibly into adjacent organs. They are rare, with little published evidence evaluating the effectiveness of radical surgery in T4 disease. MATERIAL & METHODS: Our tertiary referral centre for RCC has maintained a prospectively collected computer database since commencement in 1997. This database of 711 patients was used to identify 31 patients (4%) with T4 renal tumours. RESULTS: The patients were aged between 45 and 78, mean age 66 years. 65% were male, and 11 had distant metastases at presentation. 29 patients had details of their presentation recorded. Only 17% had incidentally detected tumours, whilst 45% had local symptoms such as loin pain, haematuria, and 38% had systemic symptoms such as weight loss or anaemia. 11 patients underwent potentially curative resections of their primary. 3 patients were referred after failed resection in a non-specialist hospital. 5 patients underwent a cytoreductive nephrectomy. 12 patients were unfit for surgery (7 with localised tumour, 5 with metastatic disease) due to poor performance status, or extensive co-morbidity. No patient underwent neoadjuvant immunotherapy. Within the curative resection group, 82% had Grade 4 tumours, and over 50% had evidence of sarcomatoid differentiation. The adjacent organ involved was most commonly psoas, followed by colon, spleen and diaphragm. The median survival in patients unfit for surgery was 7 months (range 1-18). There was a significant survival advantage for patients who underwent surgical resection of primary tumour, median 17 months, (5 – 65 months). (p=0.002 Mann-Whitney) The median survival in patients who underwent a cytoreductive nephrectomy was 27 months, (3 to 56). There was no survival advantage for patients with incidentally detected tumours when compared with symptomatic presentation. (p=0.356 Mann-Whitney). There was no difference in survival between patients with localised or metastatic disease at presentation, (p=0.836 Mann-Whitney) confirming the staging of T4 disease as Stage IV, independent of distant metastases. CONCLUSIONS: T4 tumours present a unique challenge for the surgical oncologist. Surgical resection in selected patients with good performance status can lead to a significant survival benefit for some. Due to the small numbers of T4 tumours annually and technical difficulty of complete resection these patients should be referred to a specialist renal cancer centre. UKwide collaboration is required to assess the role for neoadjuvant immunotherapy.
Ghysel C., Joniau S., Van Poppel H.
RESULTS: The population consisted of 59 patients. In all patients, primary nephrectomy was performed. Synchronous metastases were found in 16 cases and metachronous metastases in 43 cases. Overall, 74 metastasectomies with curative intent were performed: 46 patients underwent a single metastasectomy, 11 and 2 patients had metastases resected 2 and 3 times respectively. The median age at first metastasectomy was 60 years (range 2579). Metastasectomies were performed at different locations: lung n=14, adrenal n=14, bone n=12, bowel n=9, liver n=7, retroperitoneum n=5, thyroid n=4, contralateral kidney n=3, bladder n=2, other n=8. Minor complications occurred in 14 patients, major complications in 2 and 2 lethal complications occurred shortly after metastasectomy (cardiac arrest, pulmonary embolism). 5-year overall survival was 58%. Univariate Cox regression analysis identified location of metastases at the lung, DFI >2years, initial tumour stage T1 and age at first metastasectomy <60 years as significant predictors for better disease-specific survival. At multivariate Cox regression analysis, only location of metastases at the lung and the age at first metastasectomy <60 years were independently correlated with better disease-specific survival. Overall survival in repeated metastasectomy was equal to single metastasectomy. CONCLUSIONS: In a selected patient group, metastasectomy with curative intent can provide an overall 5-year survival of 58%. Age younger than 60 and location of metastases in the lung are related with an even longer survival.
P48 NEURO-UROLOGY: SENSORY MECHANISMS Friday, 7 April, 12.15-13.45, Room 242 / Level 2 796 THE ESSENCE OF URGENCY: VANILLOID RECEPTOR EXPRESSION IN WOMEN’S BLADDERS Millard R.J.1, Liu L.2, Kristiana I.2, Mansfield K.J.2, Vaux K.3, Burcher E.2 1
Prince of Wales Hospital, Urology, Sydney, Australia, 2University of New South Wales, Physiology & Pharmacology, Sydney, Australia, 3Sydney Adventist Hospital, Urology, Sydney, Australia INTRODUCTION & OBJECTIVES: Female patients with “sensory urgency” (SU): the symptom complex of urgency associated with pain, burning or discomfort, often associated with frequency and nocturia, are difficult to treat. Vanilloid receptors (TRPV1) on afferent neurons and on urothelium may participate in signalling from the bladder. Our aim was to examine whether changes in TRPV1 expression occur in bladder from SU patients compared with controls and with patients with idiopathic detrusor overactivity (IDO).
MATERIAL & METHODS: Biopsies from body and trigone were obtained from patients with SU (female, aged 21-82) who had undergone videourodynamics to exclude detrusor overactivity and define the volume at first bladder sensation. Women with recurrent proven infection were excluded. Asymptomatic age-matched females with prior history of carcinoma acted as controls. A similar cohort of women with IDO were also evaluated. Biopsies were collected into “RNALater”. Specimens were dissected into two layers, mucosa and detrusor muscle, before RNA extraction and quantitative competitive (QC) RT-PCR (Mansfield et al 2005 Br J Pharmacol 144: 1089-1099). RESULTS: In control biopsies, TRPV1 mRNA was present in greater density in mucosa than in detrusor muscle (15.3 x 105 cf. 4.6 x 105 copies/μg RNA, both n=15, P<0.01). In SU patients, TRPV1 mRNA expression was significantly higher in trigonal mucosa than in body mucosa (Table 1). There was no significant change in TRPV1 expression in body mucosa from SU specimens compared with matched controls. In SU patients, the level of TRPV1 expression in trigonal mucosa (but not body mucosa) was significantly inversely correlated (r2=0.41, P<0.01) with the volume at first bladder sensation on urodynamic testing (Fig 1A). The women with IDO showed no changes in TRPV1 expression compared with controls (Table 1) and no relation to urodynamic parameters (Fig 1B, r2=0.10, P=0.3). Table 1. The amount of TRPV1 mRNA (Median (IQR), copies x 105/μg total RNA) expressed in human bladder biopsies, determined by QC-RT-PCR. Bladder region Body mucosa
Trigonal mucosa
Control
13.8 (6.34-20.7) n = 41
N.A.
P value
SU
7.79 (4.22-20.3) n = 18
19.3 (10.6-31.7) n = 22
P < 0.01
IDO
13.7 (3.94-18.5) n = 10
11.6 (8.49-17.7) n = 13
P > 0.05
Patient group
N.A., specimens not available for ethical reasons.
CONCLUSIONS: We hypothesise that excessive afferent signalling via TRPV1 receptors in the trigone region may be related to an early first bladder sensation and sensory urgency. By contrast, the IDO bladders with symptoms of “urgency for fear of leakage” (formerly, motor urgency) have no increase in TRPV1 receptor mRNA expression. This suggests that two types of urgency exist, that they are modulated via different receptors, and that “sensory urgency” should be restored to the urological lexicon.
Eur Urol Suppl 2006;5(2):221