Abstract
Prevalence of advanced genitourinary cancer is high considering approximately 70,000 patients die annually of prostate, bladder and kidney cancer in the United States. Treatment is non-curative but along with the aim of relieving symptoms and improving quality of life, patients and doctors are driven by the goal of prolonging life. In modern urological practice, with the ever increasing number of novel therapies, clinical benefit to patients has to be measured by evaluating the trial endpoints of response and survival against adverse events. This is especially true as the population with advanced cancer is increasingly older and co-morbid. Currently, we are in a time of exponential drug development, innumerable registered trials and a vast amount of expenditure on pharmacological cancer treatment. In this era of financial uncertainty, it is even more important for clinicians to objectively assess the benefit of these expensive, moderately effective treatments that still have associated adverse sequelae. We aim to highlight the pivotal data available and put into context the survival benefit we can currently achieve with the pharmacological treatment of advanced genitourinary cancer, allowing us to critically judge whether a potentially toxic systemic treatment is worthwhile or whether it is better to defer to best supportive care. The figures presented are from the key publications that form the basis of international guideline recommendations and are the standard that newly developed treatments must emulate.
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Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Sullivan R, Peppercorn J, Sikora K et al (2011) Delivering affordable cancer care in high-income countries. Lancet Oncol 12:933–980
Chang SS (2007) Treatment options for hormone-refractory prostate cancer. Rev Urol 9(Suppl 2):S13–S18
Lu-Yao G, Moore DF, Oleynick JU et al (2007) Population based study of hormonal therapy and survival in men with metastatic prostate cancer. J Urol 177:535–539
Seidenfeld J, Samson DJ, Hasselblad V et al (2000) Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 132:566–577
Byar DP (1973) Proceeding: the veterans administration cooperative urological research group studies of cancer of the prostate. Cancer 32:1126–1130
Smith DC, Redman BG, Flaherty LE et al (1998) A phase II trial of oral diethylstilbesterol as a second-line hormonal agent in advanced prostate cancer. Urology 52:257–260
Hedlund PO, Henriksson P (2000) Parenteral estrogen versus total androgen ablation in the treatment of advanced prostate carcinoma: effects on overall survival and cardiovascular mortality. The scandinavian prostatic cancer group (SPCG)-5 trial study. Urology 55:328–333
Klotz L, McNeill I, Fleshner N (1999) A phase 1–2 trial of diethylstilbestrol plus low dose warfarin in advanced prostate carcinoma. J Urol 161:169–172
Klein D (1972) Treatment with estramustine phosphate in advanced prostatic cancer. Wien Med Wochenschr 122:458–460
Hudes G (1997) Estramustine-based chemotherapy. Semin Urol Oncol 15:13–19
Fizazi K, Le Maitre A, Hudes G et al (2007) Addition of estramustine to chemotherapy and survival of patients with castration-refractory prostate cancer: a meta-analysis of individual patient data. Lancet Oncol 8:994–1000
Tannock I, Gospodarowicz M, Meakin W et al (1989) Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol 7:590–597
Venkitaraman R, Thomas K, Huddart RA et al (2008) Efficacy of low-dose dexamethasone in castration-refractory prostate cancer. BJU Int 101:440–443
Nishimura K, Nonomura N, Yasunaga Y et al (2000) Low doses of oral dexamethasone for hormone-refractory prostate carcinoma. Cancer 89:2570–2576
Sartor O, Weinberger M, Moore A et al (1998) Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer. Urology 52:252–256
Trachtenberg J, Halpern N, Pont A (1983) Ketoconazole: a novel and rapid treatment for advanced prostatic cancer. J Urol 130:152–153
Mahler C, Verhelst J, Denis L (1993) Ketoconazole and liarozole in the treatment of advanced prostatic cancer. Cancer 71:1068–1073
Nakabayashi M, Xie W, Regan MM et al (2006) Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer. Cancer 107:975–981
Small EJ, Halabi S, Dawson NA et al (2004) Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 22:1025–1033
Nakabayashi M, Oh WK, Jacobus S et al (2010) Activity of ketoconazole after taxane-based chemotherapy in castration-resistant prostate cancer. BJU Int 105:1392–1396
Scholz M, Jennrich R, Strum S et al (2005) Long-term outcome for men with androgen independent prostate cancer treated with ketoconazole and hydrocortisone. J Urol 173:1947–1952
Tannock IF, de Wit R, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512
Berthold DR, Pond GR, Soban F et al (2008) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 26:242–245
Petrylak DP, Tangen CM, Hussain MH et al (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513–1520
de Bono JS, Oudard S, Ozguroglu M et al (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–1154
Scher HI, Beer TM, Higano CS et al (2010) Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. Lancet 375:1437–1446
Attard G, Reid AH, Yap TA et al (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 26:4563–4571
Danila DC, Morris MJ, de Bono JS et al (2010) Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol 28:1496–1501
Reid AH, Attard G, Danila DC et al (2010) Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol 28:1489–1495
Attard G, Reid AH, A’Hern R et al (2009) Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 27:3742–3748
Hussain SA, James ND (2003) The systemic treatment of advanced and metastatic bladder cancer. Lancet Oncol 4:489–497
von der Maase H, Hansen SW, Roberts JT et al (2000) Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 18:3068–3077
Loehrer PJ Sr, Einhorn LH, Elson PJ et al (1992) A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 10:1066–1073
Saxman SB, Propert KJ, Einhorn LH et al (1997) Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 15:2564–2569
Von der Maase H, Sengelov L, Roberts JT et al (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602–4608
Sternberg CN, de Mulder P, Schornagel JH et al (2006) Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 42:50–54
Stenzl A, Cowan NC, De Santis M et al (2009) The updated EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 55:815–825
Dogliotti L, Carteni G, Siena S et al (2007) Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol 52:134–141
De Santis M, Bellmunt J, Mead G et al (2009) Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer “unfit” for cisplatin-based chemotherapy: phase II–results of EORTC study 30986. J Clin Oncol 27:5634–5639
Culine S, Theodore C, De Santis M et al (2006) A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 94:1395–1401
Bellmunt J, Theodore C, Demkov T et al (2009) Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 27:4454–4461
Vishnu P, Mathew J, Tan WW (2011) Current therapeutic strategies for invasive and metastatic bladder cancer. Onco Targets Ther 4:97–113
Levi F, Ferlay J, Galeone C et al (2008) The changing pattern of kidney cancer incidence and mortality in Europe. BJU Int 101:949–958
Yang JC, Sherry RM, Steinberg SM et al (2003) Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 21:3127–3132
McDermott DF, Regan MM, Clark JI et al (2005) Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 23:133–141
Medical Research Council Renal Cancer Collaborators (1999) Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet 353:14–17
Siebels M, Rohrmann K, Oberneder R et al (2011) A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX(R)) and interferon-alpha-2a in metastatic renal cell carcinoma patients. World J Urol 29:121–126
Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124
Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134
Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590
Benedict A, Figlin RA, Sandstrom P et al (2011) Economic evaluation of new targeted therapies for the first-line treatment of patients with metastatic renal cell carcinoma. BJU Int 108:665–672
Herrmann E, Marschner N, Grimm MO et al (2011) Sequential therapies with sorafenib and sunitinib in advanced or metastatic renal cell carcinoma. World J Urol 29:361–366
Escudier B, Pluzanska A, Koralewski P et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111
Escudier B, Bellmunt J, Negrier S et al (2010) Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 28:2144–2150
Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068
Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281
Weikert S, Kempkensteffen C, Busch J et al (2011) Sequential mTOR inhibitor treatment with temsirolimus in metastatic renal cell carcinoma following failure of VEGF receptor tyrosine kinase inhibitors. World J Urol Apr 22 (Epub ahead of print)
Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456
Maclennan SJ, Maclennan SJ, Imamura M et al (2011) Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines. World J Urol 29:291–301
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Yates, D.R., Rouprêt, M. Comparing how significantly the pharmacological treatment of genitourinary cancer in a non-curative setting affects endpoints of survival or response. World J Urol 31, 117–125 (2013). https://doi.org/10.1007/s00345-011-0798-5
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DOI: https://doi.org/10.1007/s00345-011-0798-5