Minimalism might be the best choice

James Fleck & Gustavo Gössling: Anticancerweb 17(02), 2019

Prostate cancer ranks second in incidence (ARS = 29.3) among male malignancies, according to a recent international epidemiologic update, provided by the International Agency for Research on Cancer (IARC) in 2018. Fortunately, a majority indolent biological behavior and advances in palliative interventions contributed for prostate cancer longer survival, ranking fifth in malignant tumor male mortality rate (ARS = 7.6). After well-conducted local treatment, approximately 20% of prostate cancer patients express biochemical failure, manifested by a PSA increasing pattern. Gleason score > 8, PSA doubling time < 6 months, PSA velocity (>0.75 ng / mL per year), positive surgical margins and lymph node + disease are predictive factor for biochemical failure. These patients are classified as high risk and there is no consensus about the standard treatment. The successful use of docetaxel or abiraterone in the metastatic setting has been responsible for an alternative hypothesis, moving them upfront in the treatment of prostate cancer biochemical failure. Docetaxel combination with androgen deprivation therapy (ADT) based on orchiectomy or GnRH agonist / antagonist has been recently considered. 

In January, 2019 JAMA Oncology published a superiority phase III cooperative study involving 28 French centers, randomly enrolling high-risk prostate PSA-failure cancer patients in two arms. In the experimental arm patients were treated with ADT + docetaxel and in control arm the patients were subjected exclusively to ADT. Main outcome was PSA progression-free survival (PSA-PFS). PSA progression was defined as an increase of 0.2 ng / mL upon PSA baseline. The PSA response rate (PSA-R), radiological-PFS (r-PFS), overall survival, toxicity and quality of life were considered secondary end points. The results did not favor the alternative hypothesis. The addition of docetaxel to ADT did not significantly increase the PSA-PFS (HR = 0.85, P = 0.31). Likewise, there were no benefit in PSA-R, r-PFS (HR = 1.03, P = 0.88), overall survival, toxicity or quality of life. Median survival was not achieved and quality of life was in favor of exclusive ADT. In an exploratory analyses it was possible to identify that patients with more than 3 risk factors have a significant higher chance of radiological failure. 

Metanalyses, shown potential benefit with docetaxel addition, were based on studies with high index of heterogeneity. Stratification using new technology, including circulating tumor cells or cfDNA, might better identify a high-risk population, which could eventually benefit with up-scheduling treatment interventions. Meanwhile, seems reasonable to keep a minimalist approach.

Reference:

Stéphane Oudard, Igor Latorzeff, Armelle Caty, et al: Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients with High-Risk Prostate Cancer with Rising Prostate-Specific Antigen Levels After Primary Local Therapy A Randomized Clinical Trial, JAMA Oncology, January 2019

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