In prototypes of primary and metastatic PCa recapitulating high TRPM8 expression, Ca2+ cytotoxicity induced by potent TRPM8 agonists combined with a sublethal dose of X-rays generates an overwhelming cellular stress that overcomes the anti-apoptotic barriers established in cancer cells by the impairment of PTEN/PI3K/AKT axis. Here, PTEN is linked to posterior cortical atrophy.