[Does the delay from prostate biopsy to radical prostatectomy influence the risk of biochemical recurrence?] / Le delai entre biopsies de prostate et prostatectomie radicale influence-t-il le risque de recidive ?

INTRODUCTION: The influence of the delay between prostate biopsy and radical prostatectomy for patients with localized prostate cancer is controversial. The objective of this study was to establish a time limit between prostate biopsy and radical prostatectomy beyond which the risks of upgradging and biochemical recurrence (BCR) are increased. MATERIAL AND METHODS: Between January 2013 and January 2017, a retrospective analysis of the clinical, biological and histological data of 513 patients treated with radical prostatectomy for localized prostate cancer was performed in a single center. The primary endpoint was the assessment of the risk of BCR by the difference between post-biopsy USCF-CAPRA and post-surgical CAPRA-S scores. The secondary endpoint was the evaluation of the upgrading by the difference between the Gleason score on biopsy and on surgical specimen. The risks of BCR and upgrading were compared by Student test according to different delays between prostate biopsy and radical prostatectomy. The shortest delays for which a significant difference was found were reported. RESULTS: In this study, 513 patients were included. The median age at the time of the biopsy was 65 years (IQR: 60-69). The median preoperative PSA was 7.30ng/mL (IQR: 5.60-9.94). The median time between biopsy and surgery was 108 days (IQR: 86-141). For the entire cohort, the risk of BCR was significantly higher above a threshold of 90 days (P=0.039). No threshold was found for Gleason 6(3+3) patients. A 90-day threshold was found for Gleason 7(3+4) patients (P=0.038). Gleason patients≥8 had more upgrading beyond a 60-day threshold (P=0.040). CONCLUSION: Our study showed that after a 3 months delay, the risk of BCR was significantly higher for localized prostate cancer. It seemed possible to extend this period for low-risk patients, whereas it seemed necessary to keep it for intermediate-risks and to reduce it to 2 months for high-risks. LEVEL OF EVIDENCE: 4.

Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-kappaB activity.

In addition to its primary role as growth factor, human growth hormone (hGH) can also participate in cell survival, as already documented by its protective effect on human monocytes or human promyelocytic leukaemia U937 cells exposed to a Fas-mediated cell death signal. However, despite similarities in the molecular events following Fas and TNF-alpha receptor engagement, we report that U937 cells, genetically engineered to constitutively produce hGH, were made more sensitive to TNF-alpha-induced apoptosis than parental cells. This was due to overproduction of the antioxidant glutathione, which decreased the nuclear factor (NF)-kappaB activity known to control the expression of survival genes. These findings were confirmed in vivo, in nude mice bearing U937 tumours coinjected with recombinant hGH and the NF-kappaB -inducing anticancer drug daunorubicin, to avoid the in vivo toxicity of TNF-alpha. This study therefore highlights one of the various properties of hGH that may have potential clinical implications.

Human growth hormone gene transfer into tumor cells may improve cancer chemotherapy.

Chemotherapy remains the main tool for the treatment of cancers, but is often hampered by tumor cell resistance. In this context, the transfer of genes able to accentuate the effect of anticancer drugs may constitute a useful approach, as exemplified by inactivation of nuclear factor (NF)-kappa B via direct transfer of a gene encoding a negative dominant of its natural inhibitor I kappa B, leading to improved response to cancer chemotherapy. Following our previous report that transfection of human growth hormone (hGH) gene into human monocytic cell lines may also inactivate NF-kappa B in another situation, we decided to test the consequences of hGH gene transfer on cancer treatments. We demonstrated that hGH-transfected human myeloid leukemia U937 cells were sensitized to an apoptotic signal mediated by the anticancer drugs. In parallel, we found that, by inhibiting degradation of I kappa B, hGH gene transfer diminished NF-kappa B entry into the nuclei of U937 cells exposed to daunorubicin. Finally, we report that hGH-transfected tumor cells engrafted in nude mice responded in vivo to chemotherapy with nontoxic doses of daunorubicin whereas, under the same conditions, control tumor cells remained insensitive. Overall, this study therefore suggests that hGH gene transfer may offer new therapeutic prospects in cancer therapy.