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Report APPCC 2014, Melbourne, Australia by Henk van der Poel

1-2 Sept 2014

The 15th Asia-Pacific Prostate Cancer Conference was hosted by Prof. Tony Costello and Ass. Prof. Declan Murphy in Melbourne Australia. Over 500 urologists, oncologists, radiation oncologists and oncology nurses gathered in Melbourne at the end of the Australian winter. Some highlights:

Improvements in MRI imaging of lymph nodes
Dr. Jelle Barentsz, Nijmegen, The Netherlands.

The role of Combinex (a next generation Sinerem, ultrasmall iron particle) in prostate cancer oligometastases was evident from the fact that the majority (>80%) of detected metastases were smaller than 5mm in a study from Bern, Switzerland. Meijer et al. radiol oncol 2013 showed increased distant-metastases free survival in men with microscopic as compared to larger nodal metastases. Ferumoxytol (feroheam, not phagocytosed by macrophages) vs ferumoxtran-10 that showed be retained in the lymph nodes better. The future, according to Barentsz is in the combined anatomical and functional imaging provided by a combination of PET-scanning with 168Gallium-PSMA for functional data and nano-MRI. Improving early detection of metastases will be crucial if local management of oligometastases is to provide a benefit for longer term survival. For local nodal staging 7tesla imaging will further improve the anatomical detail on nodes as compared to 3tesla MRI-imaging.

PET scanning in prostate cancer
Dr. Scott Williams, Melbourne, Australia

Positron emission tomography: the principle of annihilation was presented where mass of a positron is converted into gamma radiation upon impact. If a gamma ray at 511keV is detected in a straight line at 2 positions surrounding the patient, a positron annihilation can be located reliably using tomography technology. Time-of-flight PET scanners further increase the tomographic accuracy as differences in the time both photons hit the detector reflect the distance of the annihilation of the proton to the detector and thus location. Only nanograms of the tracer are needed for specific imaging. PSMA imaging has gained renewed attention after the initial introduction of Prostascint 15 years ago. The new PSMA PET tracer does not contain an antibody but a polypeptide for rapid imaging and clearance. These new PET modalities will replace choline PET in the near future. Imaging is clearly providing earlier detection of metastases. Now have we surgical or radiotherapy means for treatment of (small) metastases of prostate cancer?

Surgery for oligometastases
Dr. Markus Graefen, Hamburg, Germany

Prostatectomy is no longer abandoned in the presence of lymph node metastasized disease. Recent studies suggest but do not prove a survival benefit for prostatectomy and node dissection in men with (limited) nodal metastases. Men with a prostatectomy seemed to fare better when metastasized disease develops later. Certainly selection bias can not be ruled out in retrospective data analyses but retrospective analyses from Europe and US suggest improved prognosis in those cases where prostatectomy is performed in the presence of nodal metastases as compared to men where prostatectomy had been abandoned in the presence of a positive nodal cryosection during the procedure. Despite these observations, men with more than 2 positive nodes still are at increased risk of progression and cancer specific mortality. Subgroup analysis from the ZEUS study on the early application of zoledronic acid for the prevention of bone metastases, it became apparent that men did better after metastases developed when the primary therapy was surgery as compared to radiotherapy. Similarly, data from the SEER database published by Shao et al., Eur Urol 2014 suggested that survival of men with metastasized prostate cancer was better when the primary therapy was prostatectomy as compared to radiotherapy. Since selection bias can not be ruled out, prospective studies are need. Several ongoing studies address the role of prostatectomy (STAMPEDE) or radiotherapy (HORRAD) in metastasized disease. The ProMPT study is studying the role of prostatectomy in M+ disease. A randomized study is in preparation for which a feasibility analysis in 103 patients showed that morbidity of prostatectomy in men with metastases is acceptable and not exceeding morbidity compared to that in men with localized disease. In the RAMPP study men with oligo metastases (= less than 4 bone metastases) will be randomized for prostatectomy + androgen ablation or androgen ablation only with as primary end point disease specific survival. The study is in preparation in Germany.

Stereotactic radiotherapy
Dr. Pat Bowden, Australia

Stereotactic radiotherapy of oligo metastases was shown successful in reducing complaints and serum PSA. An incidental long term biochemical recurrence-free survival was obtained. In Australia a prospective analysis is ongoing. The abscopal effect of radiotherapy, i.e. shrinkage of ancillary metastases in case of radiotherapy of a lesion, has been suggested but never proven. The CA184-043 study comparing metastases radiation with and without ipilimumab after docetaxel was essentially a negative trial although small volume disease patients might have benefitted and a trial in this group, without radiotherapy is ongoing. Radiotherapy on metastases may postpone the need for androgen ablation preventing early toxicity. Bowden reported on 56 patients with oligometastases that they treated with stereotactic radiotherapy with a median follow up of 4.5 months. Toxicity was low with only low-grade skin toxicity. Several cases were presented with repetitive stereotactically irradiated oligo bone and nodal metastases. Although most had biochemical recurrences androgen ablation was postponed in most of them. Data from their abovementioned prospective study is only expected in several years time.

Systemic treatment in oligometastatic disease
Dr. Ben Tran, Melbourne, Australia

Recent data from the CHAARTED study show an impressive 17 months benefit for overall survival if androgen ablation is combined with docetaxel in men with recently diagnosed high volume (>3 bone metastases, or visceral metastases) metastasized prostate cancer. CaPSURE data presented at ASCO2014 by Garcia-Albeniz showed that delayed androgen ablation in early metastases did not impact upon survival. Earlier data suggested that intermittent androgen ablation in M0 disease did not impact on survival, however, Hussain et al. NEJM 2103 showed in a randomized trial that intermittent therapy was not non-inferior to continuous disease in men with metastasized disease. Data from the docetaxel studies among which TAX327 and the CHAARTED studies suggested that low volume disease patients may not benefit from early docetaxel chemotherapy. The PREVAIL data show that both low volume disease and higher volume metastasized disease patients obtained survival benefit, contrary to chemotherapy. The role of immunotherapy has been most impressive in men with low volume metastasized disease. Sipuleucel-T and Ipilimumab both showed efficacy in post chemotherapy disease with low volume disease. The toxicity of in particular chemotherapy showed be weighted against the potential longer term benefits to overall survival.