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Re: Immediate or Deferred Androgen Deprivation for Patients with Prostate Cancer Not Suitable for Local Treatment With Curative Intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891
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european urology 50 (2006) 381–387
the BCG response remains unpredictable, and the correct moment when radical surgery should be carried out is difficult to establish.
[2] Masood S, Sriprasad S, Palmer JH, Mufti GR. T1G3 bladder cancer—indications for early cystectomy. Int Urol Nephrol 2004;36:41–4.
References [1] Thalman GN, Marckwalder R, Shahin O, Burkhard FC, Hochreiter WW, Studer UE. Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy? J Urol 2004;172:70–5.
Re: Immediate or Deferred Androgen Deprivation for Patients with Prostate Cancer Not Suitable for Local Treatment With Curative Intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891 Studer UE, Whelan P, Albrecht W, Casselman J, de Reijke T, Hauri D, Loidl W, Isorna S, Sundaram SK, Debois M, Collette L J Clin Oncol 2006;24:1868–76 Expert’s summary: In this randomised multicentric study, 985 patients with nonmetastatic prostate cancer, which also could be locally advanced (T0–4) and with positive lymph nodes (N0–2), not suitable for treatment with curative intent underwent androgen deprivation (orchiectomy or bi-monthly gonadotropin-releasing hormone analogue) either immediately or when symptoms or disease progression required it. The two groups (493 and 492 patients) were well balanced, median age was 73 yr, and the median follow-up was 7.8 yr, during which time more than 50% of the men died. Immediate androgen deprivation determined a small but statistically significant improvement in overall survival, apparently for fewer nonprostatic cancer deaths, whereas there were no differences in cancer-specific or symptom-free survival. In the deferred treatment group, the median time lag from study entry to therapy was 7 yr, and one quarter of the men died without needing treatment. The authors concluded that, in nonmetastatic prostate cancer patients, the timing of androgen deprivation should be evaluated on an individual basis, since the side-effects can be spared in a considerable number of men with a deferred treatment approach.
Joaquin A. Carballido ‘‘Puerta de Hierro’’ University Hospital, Universidad Auto´noma de Madrid, Madrid, Spain DOI: 10.1016/j.eururo.2006.05.031
ectomy in patients with advanced prostate cancer, which showed no survival difference [1]. The EORTC study’s objective was to verify if the same outcome could apply in the era of prostate-specific antigen (PSA) and analogues to men with localised disease not suitable for treatment with curative intent. A study conducted by the British Medical Research Council on 934 men is not entirely comparable, since it also included patients with asymptomatic metastatic tumours. Although its early results were in favour of immediate treatment, this finding was not confirmed with a longer follow-up [2,3]. The present study is also the first with the statistical power to test in nonmetastatic patients the equivalence between immediate or deferred androgen deprivation. A careful review of the causes of death was conducted with the help of independent experts. The authors correctly state that the cause for improved overall survival in the immediate treatment arm can only be speculated at this time, and that longer follow-up could provide the answer. However, the time to progression to hormonerefractory cancer was similar in both groups, excluding a selection bias. The same authors have recently presented a further elaboration of their data showing that, in patients with an initial PSA between 8 and 50 ng/ml, a PSA doubling time <12 mo discriminates a subgroup who is at high risk of objective progression and subsequent cancer death, and who deserve immediate treatment [4]. Therefore, besides tumor stage and grade, PSA kinetics can help the practicing urologist in selecting which patients have cancers with reduced biologic aggressiveness and, therefore, can be spared the inconveniences and cost of androgen deprivation. References
Expert’s opinion: This long-awaited EORTC study began in 1990—more than 2 decades after the original Veterans Administration studies on immediate versus deferred orchi-
[1] Byar DP. The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate. Cancer 1973;32:1126–30.
european urology 50 (2006) 381–387
[2] The Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council trial. Br J Urol 1997;79: 235–46. [3] Kirk D. Immediate vs. deferred hormone treatment of prostate cancer: how safe is androgen deprivation? Br J Urol 2000;86:S220. [4] Collette L, Studer UE, Whelan P, et al. PSA doubling time as a predictor of objective progression and death in patients
Re: Influence of Blood Transfusions during Radical Retropubic Prostatectomy on Disease Outcome Paul R, Schmidt R, Busch R, van Randenborgh H, Alschibaja M, Scholer S, Hartung R Urology 2006; 67:137–41 Expert’s summary: The authors of this paper contribute to the open debate about the possible influence of blood transfusions on the progression of prostate cancer. They attempt to establish their influence on the disease outcome. To determine a possible effect, they analysed the disease-specific survival in their series of 1412 patients submitted to radical prostatectomy over a period of 20 yr. In a retrospective study design, they determine the rate and type of blood transfusions (heterologous vs autologous) and use an appropriate statistical methodology in their analysis. The rate of transfusions decreased over the years of recruitment of the series; the overall rate was 56.7%. The differences observed in recurrence of prostate-specific antigen (PSA) and overall survival were not statistically significant (11% without vs 26% with blood transfusions) and also were not modified when they were stratified according to type and the amount of blood transfusion. In conclusion, blood transfusions in this retrospective analysis did not alter the disease outcome of patients with prostate cancer after radical prostatectomy. Expert’s opinion: This paper updates the multiple factors that can modify the evolution of a specific neoplasia in this case of localized prostate cancer. The data are informative because of the long-term follow-up. In this particular case, the influence of blood transfusion during surgery is analysed. The authors follow the working hypothesis that blood transfusions may alter mechanisms, which are related to the peroperative function of the immune system [1]. In my opinion these mechanisms have been insufficiently studied, bearing in mind that the experience we
385
with T0-4 N0-2 M0 prostate cancer not suitable for local definitive treatment or watchful waiting (EORTC 30891). Eur Urol Suppl 2006;5:203. Cesare Selli Division of Urology, Department of Surgery, Pisa University, Italy DOI: 10.1016/j.eururo.2006.05.032
have now concerning the immune characterization of patients with prostate cancer is very limited and more so in the early stages of the disease. Another factor that contributes to the interest of this study, independent of its retrospective character, is the historic value of the series because, with time and progressive experience in the technique of radical prostatectomy, the amount of blood transfusions in all the series, identical to this one, has declined more and more. This observation reinforces the interest of the results shown. The large cohort of patients analyzed and the Cox regression analysis for PSA recurrence is apt and valid to answer the objectives set out by the authors, and also to move the discussion of this problem forward because the previously available information was so contradictory that, in some cases, a negative influence was noticed and no such effect at all was noticed in others. The fact that peroperative blood transfusion was not an independent prognostic parameter of PSA recurrence is an important piece of information, and contributes to establishing differences concerning other tumours in other places and of different characteristics for which a negative effect of transfusions has been observed recently. Nevertheless, these findings should act as a stimulus to produce studies of localised prostate cancer with the aim of defining prognostic variables in the outcome of the disease, which, as in this particular case, include the immune status of the patients and not only in relation to a given neoplasia. In this sense, the parameters related to the immune state of patients and surgical treatment are representative [2]. They are traditionally hardly studied in prostate cancer patients. Their better understanding may help us to put into perspective the clinical characteristics and the evolution of prostate cancer. The outcome of such studies may suggest some indication for peroperative immunotherapy with impact on the long-term outcome of the disease, as has been seen in other neoplasias [1,3,4].
european urology 50 (2006) 381–387
the BCG response remains unpredictable, and the correct moment when radical surgery should be carried out is difficult to establish.
[2] Masood S, Sriprasad S, Palmer JH, Mufti GR. T1G3 bladder cancer—indications for early cystectomy. Int Urol Nephrol 2004;36:41–4.
References [1] Thalman GN, Marckwalder R, Shahin O, Burkhard FC, Hochreiter WW, Studer UE. Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy? J Urol 2004;172:70–5.
Re: Immediate or Deferred Androgen Deprivation for Patients with Prostate Cancer Not Suitable for Local Treatment With Curative Intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891 Studer UE, Whelan P, Albrecht W, Casselman J, de Reijke T, Hauri D, Loidl W, Isorna S, Sundaram SK, Debois M, Collette L J Clin Oncol 2006;24:1868–76 Expert’s summary: In this randomised multicentric study, 985 patients with nonmetastatic prostate cancer, which also could be locally advanced (T0–4) and with positive lymph nodes (N0–2), not suitable for treatment with curative intent underwent androgen deprivation (orchiectomy or bi-monthly gonadotropin-releasing hormone analogue) either immediately or when symptoms or disease progression required it. The two groups (493 and 492 patients) were well balanced, median age was 73 yr, and the median follow-up was 7.8 yr, during which time more than 50% of the men died. Immediate androgen deprivation determined a small but statistically significant improvement in overall survival, apparently for fewer nonprostatic cancer deaths, whereas there were no differences in cancer-specific or symptom-free survival. In the deferred treatment group, the median time lag from study entry to therapy was 7 yr, and one quarter of the men died without needing treatment. The authors concluded that, in nonmetastatic prostate cancer patients, the timing of androgen deprivation should be evaluated on an individual basis, since the side-effects can be spared in a considerable number of men with a deferred treatment approach.
Joaquin A. Carballido ‘‘Puerta de Hierro’’ University Hospital, Universidad Auto´noma de Madrid, Madrid, Spain DOI: 10.1016/j.eururo.2006.05.031
ectomy in patients with advanced prostate cancer, which showed no survival difference [1]. The EORTC study’s objective was to verify if the same outcome could apply in the era of prostate-specific antigen (PSA) and analogues to men with localised disease not suitable for treatment with curative intent. A study conducted by the British Medical Research Council on 934 men is not entirely comparable, since it also included patients with asymptomatic metastatic tumours. Although its early results were in favour of immediate treatment, this finding was not confirmed with a longer follow-up [2,3]. The present study is also the first with the statistical power to test in nonmetastatic patients the equivalence between immediate or deferred androgen deprivation. A careful review of the causes of death was conducted with the help of independent experts. The authors correctly state that the cause for improved overall survival in the immediate treatment arm can only be speculated at this time, and that longer follow-up could provide the answer. However, the time to progression to hormonerefractory cancer was similar in both groups, excluding a selection bias. The same authors have recently presented a further elaboration of their data showing that, in patients with an initial PSA between 8 and 50 ng/ml, a PSA doubling time <12 mo discriminates a subgroup who is at high risk of objective progression and subsequent cancer death, and who deserve immediate treatment [4]. Therefore, besides tumor stage and grade, PSA kinetics can help the practicing urologist in selecting which patients have cancers with reduced biologic aggressiveness and, therefore, can be spared the inconveniences and cost of androgen deprivation. References
Expert’s opinion: This long-awaited EORTC study began in 1990—more than 2 decades after the original Veterans Administration studies on immediate versus deferred orchi-
[1] Byar DP. The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate. Cancer 1973;32:1126–30.
european urology 50 (2006) 381–387
[2] The Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council trial. Br J Urol 1997;79: 235–46. [3] Kirk D. Immediate vs. deferred hormone treatment of prostate cancer: how safe is androgen deprivation? Br J Urol 2000;86:S220. [4] Collette L, Studer UE, Whelan P, et al. PSA doubling time as a predictor of objective progression and death in patients
Re: Influence of Blood Transfusions during Radical Retropubic Prostatectomy on Disease Outcome Paul R, Schmidt R, Busch R, van Randenborgh H, Alschibaja M, Scholer S, Hartung R Urology 2006; 67:137–41 Expert’s summary: The authors of this paper contribute to the open debate about the possible influence of blood transfusions on the progression of prostate cancer. They attempt to establish their influence on the disease outcome. To determine a possible effect, they analysed the disease-specific survival in their series of 1412 patients submitted to radical prostatectomy over a period of 20 yr. In a retrospective study design, they determine the rate and type of blood transfusions (heterologous vs autologous) and use an appropriate statistical methodology in their analysis. The rate of transfusions decreased over the years of recruitment of the series; the overall rate was 56.7%. The differences observed in recurrence of prostate-specific antigen (PSA) and overall survival were not statistically significant (11% without vs 26% with blood transfusions) and also were not modified when they were stratified according to type and the amount of blood transfusion. In conclusion, blood transfusions in this retrospective analysis did not alter the disease outcome of patients with prostate cancer after radical prostatectomy. Expert’s opinion: This paper updates the multiple factors that can modify the evolution of a specific neoplasia in this case of localized prostate cancer. The data are informative because of the long-term follow-up. In this particular case, the influence of blood transfusion during surgery is analysed. The authors follow the working hypothesis that blood transfusions may alter mechanisms, which are related to the peroperative function of the immune system [1]. In my opinion these mechanisms have been insufficiently studied, bearing in mind that the experience we
385
with T0-4 N0-2 M0 prostate cancer not suitable for local definitive treatment or watchful waiting (EORTC 30891). Eur Urol Suppl 2006;5:203. Cesare Selli Division of Urology, Department of Surgery, Pisa University, Italy DOI: 10.1016/j.eururo.2006.05.032
have now concerning the immune characterization of patients with prostate cancer is very limited and more so in the early stages of the disease. Another factor that contributes to the interest of this study, independent of its retrospective character, is the historic value of the series because, with time and progressive experience in the technique of radical prostatectomy, the amount of blood transfusions in all the series, identical to this one, has declined more and more. This observation reinforces the interest of the results shown. The large cohort of patients analyzed and the Cox regression analysis for PSA recurrence is apt and valid to answer the objectives set out by the authors, and also to move the discussion of this problem forward because the previously available information was so contradictory that, in some cases, a negative influence was noticed and no such effect at all was noticed in others. The fact that peroperative blood transfusion was not an independent prognostic parameter of PSA recurrence is an important piece of information, and contributes to establishing differences concerning other tumours in other places and of different characteristics for which a negative effect of transfusions has been observed recently. Nevertheless, these findings should act as a stimulus to produce studies of localised prostate cancer with the aim of defining prognostic variables in the outcome of the disease, which, as in this particular case, include the immune status of the patients and not only in relation to a given neoplasia. In this sense, the parameters related to the immune state of patients and surgical treatment are representative [2]. They are traditionally hardly studied in prostate cancer patients. Their better understanding may help us to put into perspective the clinical characteristics and the evolution of prostate cancer. The outcome of such studies may suggest some indication for peroperative immunotherapy with impact on the long-term outcome of the disease, as has been seen in other neoplasias [1,3,4].