Outcome and survival with nonsurgical management of renal cell carcinoma

Authors


A.D. Baird, Department of Urology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK.
e-mail: andy.baird@breathemail.net

Abstract

OBJECTIVE

To document long-term survival in patients with renal cell carcinoma (RCC) in whom the primary tumour was left in situ and treatment limited to palliative and symptomatic measures.

PATIENTS AND METHODS

All patients with a diagnosis of RCC from January 1994 to January 1999 and in whom the primary tumour was left in situ were identified from hospital records (nine women and 16 men, mean age 69 years). The tumour stage was T1–T4.

RESULTS

The mean survival overall was 19.3 months; patients with locally advanced disease, i.e. stage ≥ T3a, had a mean survival of 16.9 months.

CONCLUSIONS

There is renewed interest in the management of advanced RCC, with data supporting cytoreductive nephrectomy with systemic biological therapy. These results confirm that such patients with or without metastatic disease can survive for a considerable period with no aggressive surgical or systemic measures, and such intervention may offer no significant advantage in outcome and survival over supportive treatment alone.

INTRODUCTION

The incidence of RCC in the UK is 5700 cases per year [1] and about a third of patients have advanced disease at presentation [2]. For this group of patients as a whole there is no reliably effective and durable treatment offering a significant improvement in survival, except for some highly selected individuals in whom systemic immunotherapy may offer benefit. In most cases management is limited to symptomatic and palliative measures, but anecdotally some patients have a longer than expected survival. We identified patients retrospectively from hospital records between January 1994 and January 1999, with the intention of reviewing the outcome and survival of patients in whom the primary RCC was left in situ. The age, sex, mode of presentation, date of diagnosis, CT findings, TNM stage, management method, length of follow-up and outcome were documented.

PATIENTS AND METHODS

Twenty-five patients were identified (16 men and nine women, mean age 69 years, range 54–89). The mode of presentation included haematuria, loin pain, symptoms attributable to metastatic disease and those tumours discovered incidentally. All tumours were staged using CT and in 10 patients there was histopathological confirmation of the diagnosis. The tumour stage was T1–T4 (Fig. 1); there were nodal metastases in 11 and distant metastases in 14 patients. Eleven patients had symptomatic treatment only e.g. analgesia or blood transfusion, nine underwent embolization of the primary tumour to palliate haematuria, and six received radiotherapy to metastases.

Figure 1.

The tumour stage at presentation. Red hatched, women; green, men.

RESULTS

The TNM stage, management and outcome are shown in Table 1. The mean (range) survival overall was 19.3 (1–84) months. Those patients with nodal or distant metastases survived for a mean of 12.5 months. The 1-year survival was 50%. Four patients had apparently organ-confined disease but were either unfit for or refused surgery. Of 16 patients with locally advanced primary tumours (stage ≥ T3a) at presentation, two had no evidence of nodal or distant metastatic disease. The remaining 14 patients with locally advanced primary disease and metastases were of particular interest. When analysed as a subgroup, the mean (median, range) survival was 16.9 (10, 1–84) months, with patients still alive at 16, 18, 48 and 84 months from diagnosis (Fig. 2). There was no perceived survival advantage in those patients who had embolization to palliate haematuria.

Table 1.  Stage, management and outcome for the study group
No.Age (years)/sexPresentationTNM stageManagementSurvival, months
  1. SOB, shortness of breath; DXT, radiotherapy; embol, embolization; SVCO, superior vena caval obstruction.

 163/Fcough/haemoptysisT3aN1M1symptomatic16
 289/Foedema/thrombosisT2N0M0symptomatic13
 365/Mhaematuria/painT4N0M1embol × 1  4
 460/Mpelvic painT1N0M1DXT to bone met42
 567/Mweight loss/SOBT3aN1M1symptomatic11
 666/MhaematuriaT2N1M1embol × 111
 766/Mweight loss/SOBT2N0M1symptomatic
 877/Forbital massT3bN0M1DXT to met48
 970/Fhaematuria/painT3aN2M0symptomatic11
1077/MhaematuriaT3aN0M0symptomatic22
1164/Mhaematuria/massT2N0M0symptomatic55
1260/Mweight loss/neck nodeT2N1M1symptomatic17
1362/FmalaiseT3bN0M1embol × 1  9
1468/Frib swellingT2N0M1DXT to bone met13
1559/MhaematuriaT3bN1M0embol × 2  6
1654/Fbone swellingT3bN0M1DXT, embol × 1  6
1774/McoughT3bN2M1DXT for SVCO  1
1863/MhaematuriaT4N0M0embol × 1  8
1955/Mhaematuria/bone painT3bN2M1DXT, embol × 111
2086/MincidentalT1N0M0symptomatic30
2173/MincidentalT4NxMxsymptomatic18
2281/FhaematuriaT3bN1M1symptomatic  8
2382/MhaematuriaT3cN1M0embol × 2  4
2484/MincidentalT1N0M0symptomatic28
2561/Ffever/malaiseT3bN1M0embol × 184
Figure 2.

Survival related to advanced tumour stage; T3a (blue), T3b (red), T3c (green) and T4 (black).

DISCUSSION

There has been renewed interest in the management of patients presenting with advanced stage RCC, with evidence available that the use of systemic immunotherapy results in an antitumour response in some of those treated. However, there are no clear clinical or immunological markers which predict the response to immunotherapy. Results of studies assessing the use of high-dose interleukin-2 have been published, with long-term follow-up data showing a modest overall response of 15–20%[3]. Treatment regimens carry strict protocols and most have restrictions to include only those patients with no comorbid factors. Associated systemic toxicity of the treatment must also be considered. Of the current randomized trials assessing the use of interferon-α, the largest (by the MRC) [4] showed a statistically significant survival advantage in patients with metastatic RCC, the objective response rate being 14%. Overall, the use of immunotherapy is only of benefit in a highly selected minority of patients, and at the expense of the related morbidity of treatment, the response is modest at best.

The use of cytoreductive nephrectomy (CRN) before immunotherapy may prolong survival in patients with metastatic disease. The largest reported retrospective series followed 195 patients over 11 years who underwent initial nephrectomy before planned interleukin-2 therapy [5]. For various reasons, only 62% of the patients after nephrectomy were eligible for (and 55% had) immunotherapy; 22% of the patients had rapid metastatic disease progression between surgery and planned immunotherapy. Overall, the objective response rate to immunotherapy was only 18%. That study did not report long-term survival after treatment. Flanigan et al.[6] recently reported the results of the first prospective randomized controlled trial of CRN followed by immunotherapy (interferon-α), compared with immunotherapy alone. Each study arm had 123 patients, with no statistical differences in age, sex, or performance status. The outcome data show a survival advantage in those patients receiving nephrectomy before immunotherapy (mean survival 11.1 vs 8.1 months, P = 0.033), with no statistically significant difference in response to immunotherapy between the study arms. The patients in that study were highly selected on disease-specific criteria and performance status, and unfortunately there was no control arm of patients receiving symptomatic treatment only. In a similar prospective study [7], 83 patients were randomized to receive CRN plus interferon-α (arm 1, 41 patients) or interferon-α alone (arm 2, 42). Toxicity was similar in each arm and led to dose modification in 32%. The objective response rates were 19% vs 12%, respectively (P = 0.38, not significant) and the median survival was 17 vs 7 months (P = 0.03).

Finally, Bromwich et al.[8] recently reported their experiences of offering systemic therapy with interferon-α preceded by cytoreductive surgery in selected patients presenting to a regional renal cancer clinic. Of 268 patients presenting, 20 (7%) were considered appropriate for nephrectomy and then immunotherapy, with only 0.7% having any perceived clinical benefit. They concluded that as so few patients overall are considered suitable for this form of combined management, the principle of CRN is unlikely to give a significant advantage in terms of survival in a given patient population with this disease.

In conclusion, advanced RCC is regarded as a treatable and in some cases a potentially curable disease. Selecting those patients who will respond well to aggressive surgical or systemic biological therapy is extremely difficult without clear clinical or immunological markers to predict the response.

Clinicians managing patients with malignant disease should treat not only the pathology, but also the patient and the family. The results of trials assessing immunotherapy and adjunctive nephrectomy show that some individuals gain a considerable survival advantage, but the overall response rates are at best modest and the morbidity of each treatment is of major importance. Significantly, the results of the present study suggest that patients with advanced RCC with or without metastatic disease have a favourable mean survival after having symptomatic treatment alone when compared to results of CRN followed by systemic immunotherapy.

The authors accept that this retrospective observational study comprised few patients and care must be taken in comparing disease-specific treatments with individual patient-based management, but there is a clear need for further work comparing aggressive surgical and biological therapy with palliative and supportive treatment only. Until the issues in managing this disease are clear, patients receiving treatment with intention to cure should be managed only in the setting of prospective clinical trials.

Abbreviations
CRN

cytoreductive nephrectomy.

Ancillary