DRG Mutations in Prostate Cancer: a Guiding Light for Enhanced Screening and Personalised Therapy

At the present moment, there is no international consensus on the optimal screening to perform in men with a specific genetic/molecular risk for PCa. The number of studies exploring screening strategies tailored to men with a family history for PCa is limited \[15-17\]: most of them support the use of targeted screening but methodological differences make it impossible to draw conclusions from these data \[18-25\]. On the basis of these considerations, we believe extremely important to investigate a new approach to sort out men who will most benefit from early diagnosis. The optimization of such an approach could generate several benefits to the health service, by both reducing overdiagnosis and overtreatment in low-risk patients and decreasing the risk of underdiagnosis and undertreatment in genetically selected high-risk patients. Indeed, men with DRG mutations have higher grade and higher stage at time of diagnosis, limiting the possibility of care \[2\]. In the present study, we will test the hypothesis that a dedicated screening in patients with a DRG mutation, by the combination of PHI and mp-MRI, could be more effective in the PCa early detection than the current approach (DRE and PSA). We hypothesise that this targeted screening could improve the rate of early detection in PCa-positive men and increase the consequent number of curable diseases.

Sex

Male

Minimum age

35 Years

Maximum age

70 Years

Inclusion Criteria:

\- The following men will be screened for DRG mutations.

1. Males between the ages of 35 and 75 suffering from prostate cancer diagnosis with GS (Gleason Score) ≥ 4+3 willing to undergo screening for a mutation in one of the DNA repair genes (DRG);
2. Males under the age of 50 suffering from prostate cancer diagnosis with GS ≥ 3 +3 willing to undergo screening for a DRG mutation;
3. Consanguineous of males who, as a result of prostate biopsy and/or radical prostatectomy, have been diagnosed with prostate cancer with GS ≥ 4 + 3 and positive for a DRG mutation;
4. Consanguineous of males who following a prostate biopsy and/or radical prostatectomy had a diagnosis of prostatic cancer before the age of 50 with GS ≥ 3 +3 and positive for a DRG mutation.
5. Males and females older 18 yrs presenting with primary or secondary BC willing to undergo screening for a mutation in one of the DNA repair genes (DRG);
6. Males consanguineous of males and females who had a diagnosis of bladder cancer and positive for a DRG mutation
7. Males between the ages of 35 and 75 belonging to a family where a BRCA1/2 and/or DRG mutations has already been detected in at least one female (this screening has been and will be performed according to the AIOM 2019/NCCN 2019 guidelines, as for good clinical practice in our oncology center)

Exclusion Criteria:

\-