BERKELEY, CA (UroToday.com) - Oligometastatic prostate cancer is a new term recently introduced to the urologic vocabulary. In fact, recent developments of molecular and clinical imaging with better specificity and sensitivity than anatomic imaging provided clinicians with the opportunity to detect lymphatic and/or haematogenous prostatic metastases at an earlier point in the disease progression, resulting in a treatment window for oligometastatic disease. Since then, a paradigm shift toward more aggressive local control of primary tumor and/or small number of metastatic lesions has gained interest in the oncologic centers of excellence. Recently we have analyzed the evidence for local treatment of the primary tumor and/or the metastases in oligometastatic prostate cancer. As stated, there are theoretical indications and retrospective data indicating a possible benefit for treating the primary tumor in a metastatic setting. In our experience, radical prostatectomy is safe, feasible and offers good local control in well-selected metastatic patients. Apart from the debatable oncologic effect of local control, the main advantage is the symptomatic loco-regional improvement. Several complications encountered in the late stages of metastatic prostate cancer could be avoided. This could translate into an improvement in the quality of life of many patients. At present, one should bear in mind that treating the primary tumor in such patients remains outside of all urologic guidelines and should be preferably offered inside clinical trials. Another important issue is the absence of a clear definition of the oligometastatic prostate cancer state.
One could easily understand that a limited spread of the disease is always associated with a better prognosis. However, within this group of patients large differences exist in clinical progression patterns and survival rates. Several groups recently demonstrated the prognostic importance of the site of recurrence but do not specify a minimum number of lesions or distinguish between sites for initiation of metastasis-targeted therapy. In our point of view, the absolute value of PSA, PSA doubling time, and time to biochemical or clinical recurrence are also important prognostic variables to be defined in or determined from the design of clinical trials.
Metastasis-targeted therapies are found to provide patient benefit in delaying time to biochemical and clinical relapse as well as to starting ADT. In other words, they delay further disease progression and the need of systemic treatments. In the absence of prospective data on cancer-specific and overall survival, the question whether the gain in time to progression with primary control of oligometastases represents an actual benefit or progression occurs at a fixed time point in the natural course of the disease, in which the delayed time to progression is explained only by early detection, remains to be answered. Furthermore, the rather random use of a multimodality approach with adjuvant ADT and prophylactic nodal irradiation in these studies makes it difficult to make any definite conclusions.
Recently, Claeys et al. demonstrated, in adjuvant naïve patients, median PSA and clinical progression-free survival of 4.1 months and 7 months, respectively. The same authors reported projected 2 years ADT-free survival rate of 78.5%, which exceeds other oligometastatic treatment regimes with stereotactic body radiation therapy (SBRT), showing a 2-year ADT-free survival rates of 50%. One could easily argue that the difference could be due to the higher prevalence of bone metastases in the second study that are understandably associated with worse prognosis. However, we think that this difference merits some discussion. SBRT have demonstrated excellent local control with reported rates near 100% for nodal metastases and > 90% for bone metastases. Both biochemical and clinical progression can be, at least temporarily, slowed down. However, in the first published study on SBRT for isolated recurrent lymph node disease, 5 out of the 14 patients experienced out field progression. Later on, another study reported a disease-free survival rate of 17% at 3 years of follow up with 8 patients experiencing lymph node recurrences all in sites outside the irradiated areas. This stems mainly from the limited accuracy of available diagnostic tools. The sensitivity and negative predictive value of choline-PET/CT are 64% and 72%, respectively. Pathologically confirmed metastatic lymph nodes were exclusively limited to the nodes indicated by the choline-PET/CT in only 35% of patients. Furthermore, the nodes detected by choline-PET/CT might be negative in up to 25% of cases. This could explain the better results obtained by the authors when salvage lymph node dissection was performed bilaterally as a full template. In a recent review, one half of patients achieved immediate complete biologic response and one-third remained free of clinical recurrence. However, it is noteworthy to mention that the morbidity of lymph node dissection is far from trivial, particularly in the salvage setting. The role of a minimal-invasive approach is to be determined.
In contrast, the tolerability of primary and repeated salvage SBRT is reported to be excellent. Recently, a significantly higher detection rate for the (68) Gallium-Prostate Specific Membrane Antigen PET/CT compared to choline PET/CT was demonstrated, especially at low PSA levels. This could improve the negative predictive value and allow a better staging of the heterogeneous oligometastatic state.
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Fouad Aoun, MD, MSc as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Jules Bordet Institute – Université Libre de Bruxelles, Belgium