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Prostate Cancer Treatment: the Times They Are A' Changin'

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Prostate Cancer Treatment: the Times They Are A' Changin' COMMENTS be alert to the early warning signs of REFERENCES interventional bronchoscopy to avoid bronchial obstruction, noting that in practice uncontrollable bleeding: a case report this is difficult because symptoms related to 1 Braman SS, Whitcomb ME. of endobronchial metastasis of renal treatment toxicity, such as everolimus- Endobronchial metastasis. Arch Intern cell carcinoma. Intern Med 2011; 50: induced pneumonitis, may overlap with Med 1975; 135: 543–7 135–9 those of EBM. 2 Greenberg BE, Young JM. Pulmonary 8 Larkin J, Gore M. Is advanced renal cell metastasis from occult primary sites carcinoma becoming a chronic disease? Although systemic therapy appeared to resembling bronchogenic carcinoma. Dis Lancet 2010; 376: 574–5 impact little upon the clinical outcomes Chest 1958; 33: 496–505 9 Motzer RJ, Escudier B, Oudard S et al. seen in this series, delaying the onset of 3 Heitmiller RF, Marasco WJ, Hruban Efficacy of everolimus in advanced renal EBM is preferable to attempting to palliate a RH, Marsh BR. Endobronchial cell carcinoma: a double-blind, mechanical obstruction once established. metastasis. J Thorac Cardiovasc Surg randomised, placebo-controlled phase III Achieving this aim requires further 1993; 106: 537–42 trial. Lancet 2008; 372: 449–56 improvements in the systemic management 4 Kiryu T, Hoshi H, Matsui E et al. 10 Seijo LM, Sterman DH. Interventional of metastatic RCC, to delay the development Endotracheal/endobronchial metastases: pulmonology. N Engl J Med 2001; 344: of resistant disease. Most importantly, clinicopathologic study with special 740–9 clinical trials which include routine reference to developmental modes. 11 Dumon JF. A dedicated tracheobronchial assessment of tumour tissue, including Chest 2001; 119: 768–75 stent. Chest 1990; 97: 328–32 metastatic sites, at important time points 5 Dursun AB, Demirag F, Bayiz H, may identify molecular markers predictive of Sertkaya D. Endobronchial metastases: Correspondence: James M. Larkin, Medical resistance to therapy, and may also a clinicopathological analysis. Oncologist, Royal Marsden NHS Trust, distinguish those cohorts of patients at risk Respirology 2005; 10: 510–4 Fulham Road, London SW3 6JJ, UK. of developing particular complications such 6 Sakumoto N, Inafuku S, Shimoji H e-mail: [email protected] as EBM. In the meantime, oncologists faced et al. Endobronchial metastasis from with this very difficult clinical problem renal cell carcinoma: report of a case. Abbreviations: EBM, Endobronchial require careful guidance from a Surg Today 2000; 30: 744–6 metastases; mTOR, mammalian target of multidisciplinary team, which includes a 7 Suyama H, Igishi T, Makino H et al. rapamycin; VEGF, vascular endothelial respiratory physician, in the management of Bronchial artery embolization before growth factor. the individual patient. Our experience in RCC in the targeted era of treatment shows that EBM is not rare, with an incidence of ≈10%. This is in contrast to the incidence reported PROSTATE CANCER TREATMENT: THE TIMES THEY ARE A ’ in older literature, and may reflect the fact that patients treated with anti-VEGF and CHANGIN ’ Roger Kirby , Ben Challacombe * , Prokar Dasgupta * † mTOR treatments have a significantly and John M. Fitzpatrick – The Prostate Centre, London , * Guy ’ s Hospital, King ’ s improved life expectancy compared with College London, London, UK , and † the Mater Misericordiae Hospital and Irish Cancer Society, historical cohorts. Dublin, Ireland Accepted for publication 20 June 2012 CONFLICT OF INTEREST INTRODUCTION towards allaying the fears surrounding the Consultant or advisory role: James M. ‘ over-treatment ’ of clinically insignifi cant Larkin, Pfizer, Bayer, GlaxoSmithKline, Over the past few decades the treatment of tumours. Novartis; Lisa M. Pickering, Pfizer, Novartis; prostate cancer has evolved from a primarily Martin E. Gore, Pfizer, Bayer, hormonal approach, to include open and The 1966 Nobel Prize winning observation of GlaxoSmithKline, Novartis, Roche. subsequently minimally invasive radical Charles Huggins and Clarence Hodges [ 2 ] surgery and radiotherapy (RT) to newer, still that remission of prostate cancer could be Stock ownership: None. unproven, focal methods. In addition, the achieved by testosterone deprivation recent development of effective second-line constituted a landmark in the management Honoraria: James M. Larkin, Pfizer, Bayer, medical therapies, including docetaxel, of this increasingly prevalent disease. The GlaxoSmithKline, Novartis; Lisa M. Pickering, cabazitaxel and abiraterone, has resulted in next major breakthrough came when the Pfizer, Novartis, GlaxoSmithKline; Martin E. improved survival rates in men with glycoprotein PSA, secreted by columnar cells Gore, Pfizer, Bayer, GlaxoSmithKline, castration-resistant prostate cancer (CRPC) within the prostate, which liquefi es semen Novartis, Roche. [ 1 ] . The debate surrounding screening and after ejaculation, was discovered. The early detection using PSA testing continues, measurement of PSA levels in the Research funding: James M. Larkin, but the rising popularity of active bloodstream, which rise when prostate Pfizer, Bayer, Novartis; Lisa M. Pickering, surveillance (AS) as a means of managing cancer develops, resulted in a stage shift Pfizer. low-risk disease has gone some way downward in the detection of prostate 1408 © 2012 BJU INTERNATIONAL COMMENTS FIG. 1. Cabazitaxel. men who do have disease progression hormones, the PSA starts to rise. during AS by defi ning more clearly the Chemotherapy with a taxane has been Cabazitaxel triggers for intervention. shown to be effi cacious in this situation. For O OCH3 H3CO men with CRPC, the median survival in O Which treatment then should now be recent phase III studies has ranged from O O NH O offered to those men with clinically localised 12.2 to 21.7 months, with improvements in H O O OHO intermediate- or high-risk cancer deemed to survival seen mostly with docetaxel-based OH O O be at signifi cant risk of progression? regimens (8 – 11). Two studies have fi rmly Technological advances have transformed established the benefi ts of this therapy. In Systematic (IUPAC) name both surgery and RT. The development of the landmark TAX-327 trial, docetaxel (1S, 2S, 3R, 4S, 7R, 9S, 10S, 12R, 15S)-4- laparoscopic prostatectomy and more 75 mg/m 2 every 3 weeks showed a survival (Acetyloxy)-15-{[(2R,3S)-3-{[(tert- butoxy)carbonyl]amino}-2-hydroxy-3- recently robot-assisted radical advantage compared with weekly docetaxel phenylpropanoyl]oxy}-1-hydroxy-9,12- prostatectomy have reduced hospital stay, and mitoxantrone (18.9 vs 16.5 months; P < dimethoxy-10,14,17,17-tetramethyl-11-oxo-6- complication and transfusion rates, and 0.009). PSA response, pain control and oxatetracyclo[11.3.1.03,10 .04,7]heptadec-13- ene-2-yl benzoate improved the patients ’ experience of surgery health-related quality of life were also [ 6 ] and seems both oncologically sound with signifi cantly better with docetaxel given excellent functional outcomes in higher every 3 weeks compared with mitoxantrone volume centres [ 7 ] . The deployment of [ 10 ] . An update of the results of the cancer, with resultant calls for PSA intensity modulated RT (IMRT) has enhanced TAX-327 trial from 2007 confi rmed an screening. Unfortunately, PSA proved to be a targeting of RT treatment. Low-dose on-going survival benefi t with 18.6% of less than perfect marker for prostate cancer, brachytherapy is available for those patients alive at 3 years, for the docetaxel because of the very large number of men unwilling to consider either surgery or the group compared with 13.5% with with BPH, with similarly raised PSA values. 7-week daily treatment regime required mitoxantrone (P = 0.005) [ 11 ] . Nonetheless, the European Randomised for IMRT and can be given as a boost to Study of Prostate Cancer Screening (ERSPC), IMRT for those with intermediate/high-risk A study by the Southwest Oncology Group initiated in the 1990s, has recently reported disease wishing to avoid hormonal ablation. (SWOG) 99-16 also showed survival benefi t a 21% reduction in prostate cancer For locally advanced tumours most agree with docetaxel of 17.5 vs 15.6 months for mortality in the screened arm at 11 years that external-beam RT preceded by 3 mitoxantrone (P = 0.02), with a median time [ 3 ] , but at the price of a considerable months of androgen deprivation is the best to progression (6.3 vs 3.2 months; P < ‘ over-diagnosis ’ of low-risk, clinically alternative. 0.001) and PSA declines of 50% (50% vs insignifi cant cancers. 27%; P < 0.001) [ 12 ] . These two trials Very recently there has been a fl urry of showed a 20 – 24% reduction in mortality in ‘ Over-diagnosis ’ of prostate cancer is only publicity about focal treatment of localised patients with CRPC treated with docetaxel- worrisome if it results in ‘ over-treatment ’. prostate cancer using high-intensity focused based chemotherapy. Most reported series of radical ultrasound (HIFU). A recent publication [ 8 ] prostatectomy and RT treatments for reported data at 1 year in 42 patients There is now new hope for patients who localised prostate cancer undoubtedly treated with minimal impact on either progress after docetaxel-based contained a proportion of patients with sexual function or continence. However, four chemotherapy. A new generation taxane, low-risk cancers that may never have patients required re-treatment and others cabazitaxel, is now available to overcome progressed within their natural lifespan. might be anticipated to relapse with further
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