25
Volume 68 December 1975
775
Section of Urology President G C Tresidder FRCS
Meeting 27 February 1975
Management of Metastatic Renal Carcinoma Mr G D Chisholm (Hammersmith Hospital, London W12 and St Peter's Hospitals, London)
Surgical Aspects The management of metastases from renal cell tumours continues to challenge the clinician. In addition to the vagaries of presentation (Chisholm 1974a) and the unpredictable natural history, these metastases are also of interest because some may be solitary and suitable for excision, while others may respond to hormone therapy; there is also the occasional spontaneous disappearance of metastases (Bloom 1973). Having made the diagnosis, the urologist must decide on the operability of the primary tumour, the relevance of radiotherapy and the management of both local and distant spread of the tumour. Most of the surgical problems relate to the spread to regional lymph nodes and to the renal vein and vena cava. Less commonly, distant spread to organ sites may also be surgically treatable especially when localized either to the lung or to a bone. Finally, the urologist may be confronted with a patient with biochemical 'evidence' of distant metastatic disease (for example, abnormal liver function tests) with no demonstrable tumour other than the primary lesion. Investigation The management of a renal tumour requires as much preliminary information as possible in order to obtain accurate preoperative staging and to plan the optimum surgical approach. It is for this reason that the UICC recommendations for the classification of renal tumours have the following minimal requirements (Wallace et al. 1975): T (Tumour): Clinical examination. Urography. Arteriography. (The need for arteriography emphasizes the well-recognized limitations of the clinical assessment of a renal mass.) N (Nodes): Clinical examination. Lymphography. Urography. (The regional nodes are para-aortic and
paracaval; juxtaregional nodes are intrapelvic and mediastinal.) M (Metastases): Clinical examination. Chest X-ray. Biochemical tests. Radiographic or isotopic bone study. Other investigations such as perineal pneumography and mediastinoscopy have been advocated but are not generally used. It is far simpler and more reliable to include tomography with the radiological examination of the chest. The use of vena cavography to demonstrate the full extent of a caval extension must also be included if an attempt is to be made to remove such an extension (see below). However, valuable information on the patency of the renal vein can be gained from the venous phase of a renal angiogram. Local Metastases: Lymph Nodes Until 1948, simple nephrectomy through a loin incision was the accepted treatment for a renal tumour and in the main reported series the fiveyear survival rate was 40-50 % and the ten-year survival rate was 20-30 % (Skinner, Vermillion & Colvin 1972). Because of the high mortality rate and difficulty with the operative procedure many urologists came to prefer a transperitoneal approach with early dissection and clamping of the pedicle. Both Mortensen (1948) and Chute et al. (1949) have advocated a thoraco-abdominal approach so that large masses with their perinephric envelope could be removed. None of these changes in surgical technique made special reference to the lymphatic drainage until Robson (1963) emphasized the value of a radical excision together with the regional lymph nodes; and his recent results show superior survival compared with other series both at five years (57 %) and at ten years (53 %) and have led him to state that the 'only important advance in the therapy of this tumor has been achieved through radical nephrectomy' (Robson 1972). The proportion of cases reported to have lymph node involvement has varied from 5 % to 33 %. However, unless a full dissection is carried out,
776 Proc. roy. Soc. Med. Volume 68 December 1975 the true incidence and localization is unknown. Recently, Hulten et al. (1969) carried out such a study in 22 patients and found the incidence of metastases in lumbar and homolateral iliac lymph nodes to be 27 %; in some cases the metastases were found in iliac or supraclavicular nodes only, i.e. without evidence of spread to the regional nodes. There was no true correlation between lymphographic signs and histologically proven metastases though the procedure was considered helpful, using X-ray control, in carrying out the lymphadenectomy. It was also noted that there were no lymphatic metastases in those cases where the tumour diameter was less than 6.5 cm. It is relevant to note that Arkless (1965) found that when the regional lymph nodes were palpable there were always concomitant lung seedlings. It must be concluded that the routine dissection of regional lymph nodes is not always indicated; when it is, however, a full node dissection should include homolateral common iliac nodes and even supraclavicular nodes. The published data on the radical operation indicate that results are improved for locally extensive disease but it is also evident that there are low salvage rates in most patients with high stage and grade tumours. Local Metastases: Renal Veinl Vena Cava The incidence of local spread into the renal vein has been reported as approximately 50 % and the incidence of vena caval involvement is 5-10 %. In the absence of vena cavography, most urologists continue to rely on the early inspection of the renal vein at nephrectomy, to establish the extent of tumour involvement. If there is an extension, the tongue of tumour can usually be drawn or sucked back through the renal vein. A more aggressive approach requires vena cavography as well as preparation for an operation that may require extensive exposure of the vena cava including a thoracotomy. Skinner, Pfister & Colvin (1972) have reported the successful removal of tumour that completely occluded the vena cava and extended into the right atrium. Others have recommended vena caval resection with the renal tumours, en bloc, when the tumour thrombus either invades or adheres to the cava (McCullough & Gittes 1974). The effect of such surgical efforts on survival rates is encouraging, though numbers are small. Whereas five-year survival rates of 30-40 % have been reported with renal vein involvement, Skinner, Pfister & Colvin (1972) have reported that 5 out of 11 cases treated by extensive caval surgery have survived five years. It may be concluded that while the removal of an extension of tumour into the vena cava is feasible, we must await the results from a much larger study to determine whether or not patients so treated have an improved survival rate.
26 Distant Metastases: Organ Sites Solitary metastases have been removed surgically from a remarkable variety of sites: in alphabetical order - bladder, bone, brain, breast, bronchus, colon, heart, jejunum, kidney, lung, cesophagus, thyroid, vagina, wound (nephrectomy) (Kaufman & Mims 1966, Middleton 1967, Ochsner et al. 1973). Many have been removed by a planned procedure because there was an apparently solitary metastasis; in other instances, the relationship to the primary tumour was revealed only after its removal and histological examination. Sometimes, the details of the previous nephrectomy may not be known or the time interval may seem too remote to be relevant; for example, the reported wound metastasis developed 31 years after the nephrectomy. The decision to excise a metastasis will always be influenced by the general condition of the patient but, whenever possible, excision of a solitary lesion is preferred to local radiotherapy. As with surgery of venous tumour spread, there is a trend towards a more aggressive approach to solitary lesions. Robinson & Jacobson (1965) have reported a patient who, in the space of four years, underwent excision of a solitary metastasis in the left third rib, in the right humerus (disarticulation), and in lung (lower lobectomy) and was alive and well three years later. Solitary metastases in bone have occurred in a wide variety of sites (in order of frequency) humerus, spine, femur, pelvis, ribs, foot bones, skull, sternum, clavicle. While those occurring in long bones are likely to be more suitable for surgery, metastases in the vertebral column have been successfully treated. A metastasis in some bony sites, such as the nasal septum, is more suited for radiotherapy. In a major review of surgery for distant metastases Middleton (1967) reported 59 cases, 50 from the literature; there was a 45 % three-year survival and a 34 % five-year survival. Just over 50% in this series were solitary lung lesions with a range of survival from months to 23 years. This range of survival was similar to that for other organ sites. A consistent feature was that most of the patients who died did so from metastases. In assessing the effect of surgery for metastases on survival rates we are continually faced with the remarkable variation in the natural history of both primary and secondary disease. It is evident from all reported series that patients with known metastatic disease at the time of nephrectomy rarely survive more than three years. Nevertheless, excision of the primary tumour mass in these advanced cases should continue to be recommended for there is often considerable subjective improvement as well as relief of pain and hmematuria. There may be, very occasionally, spontaneous remission of the metastases. In contrast,
27
777
Section of Urology
the prognosis with late appearing metastases Carcinoma of the Penis appears to be quite good but it is possible that this is more a reflection of the grade of tumour Dr H Hope-Stone and/or host tumour control (Riches 1963). (London Hospital, London El JBB) Distant Metastases and Relevance External Radiation Mould Technique of Systemic Effects It is well recognized that renal tumours can Undoubtedly the early case of carcinoma of the produce both nonspecific as well as specific penis should be treated by irradiation and not (endocrine) systemic effects (Chisholm 1974b). surgery, since the results are at least as good, Formerly, many of these effects were considered and cosmetically and psychologically there is 'medical' complications of renal cell carcinoma everything to be gained: not only may the patient and it was implied that many were due to the continue to micturate in the normal way, but in advanced stage of the disease. Thus, for example, the younger man normal sexual intercourse can abnormal liver function tests, hypertension and always be achieved. Surgery has its own morbidity hypercalcx,mia were thought to be late manifesta- and even mortality rate: in the London Hospital tions of the disease and therefore, contra- series we even had one man of 80 who preferred irradiation to surgery because, as he put it, 'the indications to nephrectomy. It is now known that few of the systemic patient in the bed next to him had an amputation effects are necessarily evidence of metastatic of the penis and died on the third post-operative disease. Since the tumour itself may be the sole day'. Another advantage of irradiation is the cause of the abnormalities, excision of the primary possibility of salvage surgery for recurrence, tumour should now be recommended in all cases. whereas after failed surgery radical external Furthermore, the disappearance of the ab- irradiation is usually impossible. normality indicates a favourable prognosis, while its reappearance usually coincides with recurrence. Technique Thus the detection of either biochemical The technique at The London Hospital follows 'evidence' of distant metastases or other systemic that originally described by Paterson (1963), with effects should not influence either the initial or some modifications and change of radioactive the subsequent surgical management of patients sources (i.e. the use of iridium wire instead of radium needles). with renal cell carcinoma. The type of lesion suitable for treatment by REFERENCES this technique is a Stage 1 tumour (Fig 1), conArkless R (1965) Radiology 84,496 fined to the glans or prepuce and not involving Bloom H J G (1973) Cancer 32, 1066 Chisholm G D the corpus cavernosum or urethra, and preferably (1974a) Annals of the Royal College of Surgeons ofEngland 55, 21 (1974b) Annals ofthe New York Academy of Sciences 230,403 Chute R, Soutter L & Kerr W S jr (1949) New EnglandJournal of Medicine 241, 951 Hulten L, Rosencrantz M, Seeman T, Wahlqvist L & Ahren C (1969) Scandinavian Journal of Urology and Nephrology 3, 129
Kaufman J J & Mims M D (1966) Current Problems in Surgery p 1 McCullough D L & Gittes R F (1974) Journal of Urology 112, 162 Middleton R G (1967) In: Renal Neoplasia. Ed. J S King jr. Churchill, London; p 483 Mortensen H (1948) Journal of Urology 60, 855 Ochsner M G, Brannan W, Pond H S & Goodier E H (1973) Journalpf Urology 110, 643 Riches E W (1963) Annals of the Royal College ofSurgeons ofEngland 32, 201 Robinson F W & Jacobson M E (1965) Journal ofthe Kansas Medical Society 66, 460 Robson C J (1963) Journal of Urology 89, 37 (1972) In: Current Controversies in Urologic Management. Ed. R Scott. Saunders, Philadelphia; p 33 Skinner D G, Pfister R F & Colvin R B (1972) Journal of Urology 107, 71 1 Skinner D V, Vermillion C D & Colvin R B (1972) Journal oJ Urology 107, 705 Wallace D M, Chisholm G D & Hendry W F (1975) British Journal of Urology 47, 1
i~~~ 1
F.r. s c
Endocrine Aspects were discussed by Dr H J G Bloom (Royal Marsden Hospital, London) and Radiotherapy by Dr D G Bratherton (Addenbrooke's Hospital, Cambridge) Fig 1 Primary squamous cell carcinoma ofpenis
Volume 68 December 1975
775
Section of Urology President G C Tresidder FRCS
Meeting 27 February 1975
Management of Metastatic Renal Carcinoma Mr G D Chisholm (Hammersmith Hospital, London W12 and St Peter's Hospitals, London)
Surgical Aspects The management of metastases from renal cell tumours continues to challenge the clinician. In addition to the vagaries of presentation (Chisholm 1974a) and the unpredictable natural history, these metastases are also of interest because some may be solitary and suitable for excision, while others may respond to hormone therapy; there is also the occasional spontaneous disappearance of metastases (Bloom 1973). Having made the diagnosis, the urologist must decide on the operability of the primary tumour, the relevance of radiotherapy and the management of both local and distant spread of the tumour. Most of the surgical problems relate to the spread to regional lymph nodes and to the renal vein and vena cava. Less commonly, distant spread to organ sites may also be surgically treatable especially when localized either to the lung or to a bone. Finally, the urologist may be confronted with a patient with biochemical 'evidence' of distant metastatic disease (for example, abnormal liver function tests) with no demonstrable tumour other than the primary lesion. Investigation The management of a renal tumour requires as much preliminary information as possible in order to obtain accurate preoperative staging and to plan the optimum surgical approach. It is for this reason that the UICC recommendations for the classification of renal tumours have the following minimal requirements (Wallace et al. 1975): T (Tumour): Clinical examination. Urography. Arteriography. (The need for arteriography emphasizes the well-recognized limitations of the clinical assessment of a renal mass.) N (Nodes): Clinical examination. Lymphography. Urography. (The regional nodes are para-aortic and
paracaval; juxtaregional nodes are intrapelvic and mediastinal.) M (Metastases): Clinical examination. Chest X-ray. Biochemical tests. Radiographic or isotopic bone study. Other investigations such as perineal pneumography and mediastinoscopy have been advocated but are not generally used. It is far simpler and more reliable to include tomography with the radiological examination of the chest. The use of vena cavography to demonstrate the full extent of a caval extension must also be included if an attempt is to be made to remove such an extension (see below). However, valuable information on the patency of the renal vein can be gained from the venous phase of a renal angiogram. Local Metastases: Lymph Nodes Until 1948, simple nephrectomy through a loin incision was the accepted treatment for a renal tumour and in the main reported series the fiveyear survival rate was 40-50 % and the ten-year survival rate was 20-30 % (Skinner, Vermillion & Colvin 1972). Because of the high mortality rate and difficulty with the operative procedure many urologists came to prefer a transperitoneal approach with early dissection and clamping of the pedicle. Both Mortensen (1948) and Chute et al. (1949) have advocated a thoraco-abdominal approach so that large masses with their perinephric envelope could be removed. None of these changes in surgical technique made special reference to the lymphatic drainage until Robson (1963) emphasized the value of a radical excision together with the regional lymph nodes; and his recent results show superior survival compared with other series both at five years (57 %) and at ten years (53 %) and have led him to state that the 'only important advance in the therapy of this tumor has been achieved through radical nephrectomy' (Robson 1972). The proportion of cases reported to have lymph node involvement has varied from 5 % to 33 %. However, unless a full dissection is carried out,
776 Proc. roy. Soc. Med. Volume 68 December 1975 the true incidence and localization is unknown. Recently, Hulten et al. (1969) carried out such a study in 22 patients and found the incidence of metastases in lumbar and homolateral iliac lymph nodes to be 27 %; in some cases the metastases were found in iliac or supraclavicular nodes only, i.e. without evidence of spread to the regional nodes. There was no true correlation between lymphographic signs and histologically proven metastases though the procedure was considered helpful, using X-ray control, in carrying out the lymphadenectomy. It was also noted that there were no lymphatic metastases in those cases where the tumour diameter was less than 6.5 cm. It is relevant to note that Arkless (1965) found that when the regional lymph nodes were palpable there were always concomitant lung seedlings. It must be concluded that the routine dissection of regional lymph nodes is not always indicated; when it is, however, a full node dissection should include homolateral common iliac nodes and even supraclavicular nodes. The published data on the radical operation indicate that results are improved for locally extensive disease but it is also evident that there are low salvage rates in most patients with high stage and grade tumours. Local Metastases: Renal Veinl Vena Cava The incidence of local spread into the renal vein has been reported as approximately 50 % and the incidence of vena caval involvement is 5-10 %. In the absence of vena cavography, most urologists continue to rely on the early inspection of the renal vein at nephrectomy, to establish the extent of tumour involvement. If there is an extension, the tongue of tumour can usually be drawn or sucked back through the renal vein. A more aggressive approach requires vena cavography as well as preparation for an operation that may require extensive exposure of the vena cava including a thoracotomy. Skinner, Pfister & Colvin (1972) have reported the successful removal of tumour that completely occluded the vena cava and extended into the right atrium. Others have recommended vena caval resection with the renal tumours, en bloc, when the tumour thrombus either invades or adheres to the cava (McCullough & Gittes 1974). The effect of such surgical efforts on survival rates is encouraging, though numbers are small. Whereas five-year survival rates of 30-40 % have been reported with renal vein involvement, Skinner, Pfister & Colvin (1972) have reported that 5 out of 11 cases treated by extensive caval surgery have survived five years. It may be concluded that while the removal of an extension of tumour into the vena cava is feasible, we must await the results from a much larger study to determine whether or not patients so treated have an improved survival rate.
26 Distant Metastases: Organ Sites Solitary metastases have been removed surgically from a remarkable variety of sites: in alphabetical order - bladder, bone, brain, breast, bronchus, colon, heart, jejunum, kidney, lung, cesophagus, thyroid, vagina, wound (nephrectomy) (Kaufman & Mims 1966, Middleton 1967, Ochsner et al. 1973). Many have been removed by a planned procedure because there was an apparently solitary metastasis; in other instances, the relationship to the primary tumour was revealed only after its removal and histological examination. Sometimes, the details of the previous nephrectomy may not be known or the time interval may seem too remote to be relevant; for example, the reported wound metastasis developed 31 years after the nephrectomy. The decision to excise a metastasis will always be influenced by the general condition of the patient but, whenever possible, excision of a solitary lesion is preferred to local radiotherapy. As with surgery of venous tumour spread, there is a trend towards a more aggressive approach to solitary lesions. Robinson & Jacobson (1965) have reported a patient who, in the space of four years, underwent excision of a solitary metastasis in the left third rib, in the right humerus (disarticulation), and in lung (lower lobectomy) and was alive and well three years later. Solitary metastases in bone have occurred in a wide variety of sites (in order of frequency) humerus, spine, femur, pelvis, ribs, foot bones, skull, sternum, clavicle. While those occurring in long bones are likely to be more suitable for surgery, metastases in the vertebral column have been successfully treated. A metastasis in some bony sites, such as the nasal septum, is more suited for radiotherapy. In a major review of surgery for distant metastases Middleton (1967) reported 59 cases, 50 from the literature; there was a 45 % three-year survival and a 34 % five-year survival. Just over 50% in this series were solitary lung lesions with a range of survival from months to 23 years. This range of survival was similar to that for other organ sites. A consistent feature was that most of the patients who died did so from metastases. In assessing the effect of surgery for metastases on survival rates we are continually faced with the remarkable variation in the natural history of both primary and secondary disease. It is evident from all reported series that patients with known metastatic disease at the time of nephrectomy rarely survive more than three years. Nevertheless, excision of the primary tumour mass in these advanced cases should continue to be recommended for there is often considerable subjective improvement as well as relief of pain and hmematuria. There may be, very occasionally, spontaneous remission of the metastases. In contrast,
27
777
Section of Urology
the prognosis with late appearing metastases Carcinoma of the Penis appears to be quite good but it is possible that this is more a reflection of the grade of tumour Dr H Hope-Stone and/or host tumour control (Riches 1963). (London Hospital, London El JBB) Distant Metastases and Relevance External Radiation Mould Technique of Systemic Effects It is well recognized that renal tumours can Undoubtedly the early case of carcinoma of the produce both nonspecific as well as specific penis should be treated by irradiation and not (endocrine) systemic effects (Chisholm 1974b). surgery, since the results are at least as good, Formerly, many of these effects were considered and cosmetically and psychologically there is 'medical' complications of renal cell carcinoma everything to be gained: not only may the patient and it was implied that many were due to the continue to micturate in the normal way, but in advanced stage of the disease. Thus, for example, the younger man normal sexual intercourse can abnormal liver function tests, hypertension and always be achieved. Surgery has its own morbidity hypercalcx,mia were thought to be late manifesta- and even mortality rate: in the London Hospital tions of the disease and therefore, contra- series we even had one man of 80 who preferred irradiation to surgery because, as he put it, 'the indications to nephrectomy. It is now known that few of the systemic patient in the bed next to him had an amputation effects are necessarily evidence of metastatic of the penis and died on the third post-operative disease. Since the tumour itself may be the sole day'. Another advantage of irradiation is the cause of the abnormalities, excision of the primary possibility of salvage surgery for recurrence, tumour should now be recommended in all cases. whereas after failed surgery radical external Furthermore, the disappearance of the ab- irradiation is usually impossible. normality indicates a favourable prognosis, while its reappearance usually coincides with recurrence. Technique Thus the detection of either biochemical The technique at The London Hospital follows 'evidence' of distant metastases or other systemic that originally described by Paterson (1963), with effects should not influence either the initial or some modifications and change of radioactive the subsequent surgical management of patients sources (i.e. the use of iridium wire instead of radium needles). with renal cell carcinoma. The type of lesion suitable for treatment by REFERENCES this technique is a Stage 1 tumour (Fig 1), conArkless R (1965) Radiology 84,496 fined to the glans or prepuce and not involving Bloom H J G (1973) Cancer 32, 1066 Chisholm G D the corpus cavernosum or urethra, and preferably (1974a) Annals of the Royal College of Surgeons ofEngland 55, 21 (1974b) Annals ofthe New York Academy of Sciences 230,403 Chute R, Soutter L & Kerr W S jr (1949) New EnglandJournal of Medicine 241, 951 Hulten L, Rosencrantz M, Seeman T, Wahlqvist L & Ahren C (1969) Scandinavian Journal of Urology and Nephrology 3, 129
Kaufman J J & Mims M D (1966) Current Problems in Surgery p 1 McCullough D L & Gittes R F (1974) Journal of Urology 112, 162 Middleton R G (1967) In: Renal Neoplasia. Ed. J S King jr. Churchill, London; p 483 Mortensen H (1948) Journal of Urology 60, 855 Ochsner M G, Brannan W, Pond H S & Goodier E H (1973) Journalpf Urology 110, 643 Riches E W (1963) Annals of the Royal College ofSurgeons ofEngland 32, 201 Robinson F W & Jacobson M E (1965) Journal ofthe Kansas Medical Society 66, 460 Robson C J (1963) Journal of Urology 89, 37 (1972) In: Current Controversies in Urologic Management. Ed. R Scott. Saunders, Philadelphia; p 33 Skinner D G, Pfister R F & Colvin R B (1972) Journal of Urology 107, 71 1 Skinner D V, Vermillion C D & Colvin R B (1972) Journal oJ Urology 107, 705 Wallace D M, Chisholm G D & Hendry W F (1975) British Journal of Urology 47, 1
i~~~ 1
F.r. s c
Endocrine Aspects were discussed by Dr H J G Bloom (Royal Marsden Hospital, London) and Radiotherapy by Dr D G Bratherton (Addenbrooke's Hospital, Cambridge) Fig 1 Primary squamous cell carcinoma ofpenis
