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Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.2.448 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10637263 Mack Roach IIIxMack Roach IIISearch for articles by this author , David ReesexDavid ReeseSearch for articles by this author , Vivian WeinbergxVivian WeinbergSearch for articles by this author , Eric J. SmallxEric J. SmallSearch for articles by this author , Peter R. CarrollxPeter R. CarrollSearch for articles by this author Francesco BoccardoxFrancesco BoccardoSearch for articles by this author , Alessandra RubagottixAlessandra RubagottiSearch for articles by this author Show More University of CaliforniaSan Francisco San Francisco, CAOn behalf of the Italian Prostate Cancer Project University and National Cancer Institute GenoaItaly https://doi.org/10.1200/JCO.2000.18.2.448 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01012000In Reply:While we share the caution expressed by Roach et al, we disagree with most of the points raised by them.First, we never used the term equivalent to define the results achieved by bicalutamide monotherapy in our trial. This is a misinterpretation of our conclusions. We just limited to recognize that the results achieved by bicalutamide were comparable to those achieved by maximum androgen deprivation.Roach et al are correct in saying that trial amendment (which was required for ethical reasons) did further weaken the power of the trial. However, they are probably wrong in stating that “trial design was altered” and that amendment “led to potential biases in interpretation.” In fact, as it is clearly stated in the article,1 different lists of randomization were available by disease stage. Moreover, only 11 patients with stage C disease were entered since the date of amendment.There is no doubt that there are marked differences in the prognosis of patients with stage C and those with stage D. For this reason, separate analyses by stage were provided in the article (Fig 4 and Table 2) together with an analysis of all patients.1 The imbalances in treatment arms recalled by Roach et al were not significant and were “corrected” through multivariate analysis. As it is clearly stated in the article, patient age, initial alkaline phosphatase level, and baseline hemoglobin level were included in the model in addition to baseline prostate-specific antigen level, disease stage, and tumor grade.1 The analysis of paired data for changes in hemoglobin level relative to the patients for whom baseline, 3-month, and 6-month data were available are reported in Table 1. Hemoglobin Levels at the Start of Treatment and at 3 and 6 Months after Treatment (paired data)Hemoglobin Levels at the Start of Treatment and at 3 and 6 Months after Treatment (paired data)No. of PatientsHemoglobin Levels (g/dL)T0T3T6NOTE. Data are expressed as mean ± SE.Abbreviation: NS, not significant.Bicalutamide4813.7 ± 0.3113.7 ± 0.2313.8 ± 0.22Goserelin + flutamide5613.8 ± 0.2512.7 ± 0.2112.8 ± 0.21PNS.003.002Findings are almost identical to those reported in Table 4 in the article1 and in our opinion do not require further comment.Evaluation of QoL was not the primary end point of this study, and we already recognized that “the reliability of QoL analysis might be biased by the low compliance of patients.” However, our results are enforced by those reported on in this regard in the previous trials comparing bicalutamide monotherapy with castration.2,3 Moreover, data on sexual functioning were drawn after all patients were interviewed, and there is no doubt that fewer patients in the bicalutamide group complained of loss of libido and erectile dysfunction. This finding is common to the majority of previous trials reporting on pure antiandrogen monotherapy.2-5Loss of sexual potency has proved to be of special concern for younger men. An estimation of the perception of sexual dysfunction as an event negatively influencing QoL comes from the studies performed in men treated either with surgery or with radiotherapy for localized or locally advanced disease. Comparative trials have shown that the decline in sexual function was the most common cause of disease-specific stress among men with prostate cancer.6 Singer et al7 reported that of a sample of 50 men without known prostate cancer, 68% were willing to trade a 10% or greater advantage in 5-year survival in order to maintain sexual potency. A larger trial of 230 men in a general medicine clinic supported this finding, with 67% of men stating they would be willing to trade an increase of 14% in survival time in order to prevent impotence.8If it is acceptable, at least in principle, that men who are virtually candidates for cure might trade an increase of 10% or more in expected survival in order to prevent impotence, why should we not accept that men who are no longer candidates to be cured of their disease, like those with locally advanced or metastatic disease, could be willing to trade a modest (42 days in the trials of bicalutamide v castration,2) deficit in expected survival to achieve the same goal? Of course, the balance of risk and benefit should be integral to the discussion between the patient and the physician. However, not informing patients about the possible alternatives to androgen deprivation could limit their ability to choose. It has been said that a distinguished Italian surgeon in the 1970s chose to die of his prostate cancer because he did not want to accept the consequences of androgen deprivation. Let’s believe that should this gentleman be born 20 years later, he would probably live longer (and maybe die of a competing cause!) and benefit from a more appropriate palliation of his disease thanks to antiandrogen monotherapy.7. Boccardo F, Rubagotti A, Barichello M, et al: Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: Results of an Italian Prostate Cancer Project study. J Clin Oncol 17::2027,1999-2038, Link, Google Scholar7. Tyrrell CJ, Kaisary AV, Iversen P, et al: A randomised comparison of ‘Casodex’ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 33::447,1998-456, Crossref, Medline, Google Scholar7. Iversen P, Tyrrell CJ, Kaisary AV, et al: Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: Results from two multicenter randomized trials at a median follow-up of 4 years. Urology 51::389,1998-396, Crossref, Medline, Google Scholar7. Kaisary AV: Antiandrogen monotherapy in the management of advanced prostate cancer. Eur Urol 31::14,1997-19, (suppl 2) Crossref, Medline, Google Scholar7. Migliari R, Muscas G, Usai E: Effect of Casodex on sleep-related erections in patients with advanced prostate cancer. J Urol 148::338,1992-341, Crossref, Medline, Google Scholar7. Helgason AR, Adolfsson J, Dickman P, et al: Sexual desire, erection, orgasm and ejaculatory functions and their importance to elderly Swedish men: A population-based study. Age Ageing 25::285,1996-291, Crossref, Medline, Google Scholar7. Singer PA, Tasch ES, Stocking C, et al: Sex or survival: Trade-offs between quality and quantity of life. J Clin Oncol 9::328,1991-334, Link, Google Scholar7. Mazur DJ, Hickham DH: Patient preferences: Survival versus quality of life. J Gen Intern Med 8::374,1993-377, Crossref, Medline, Google Scholar