Since the dependence of prostate cancer on androgen signaling firstly discovered by Huggins and Hodges, hormonal therapy has been considered as the standard treatment for locally advanced and metastatic prostate cancer. AHT aimed to improve the long-term survival of patients with high-risk localized prostate cancer, positive surgical margin, and pathologically positive lymph nodes[18, 23]. Although some retrospective studies showed that AHT cannot provide significant prognostic benefits in patients with minimal nodal[12, 24], a RCT demonstrated that early AHT provides significantly CCS and OS improvement in high-risk prostate cancer . The finding suggested RP plus postoperative AHT was an important component of multimodal strategies for high-risk prostate cancer. Unfortunately, though AHT could control the development of the disease for several years, most of these patients would experience recurrence and even death, which is consistent with our survival surveillance data.
Quite a few scholars believe that one reason for the resistant to ADT is the generation of AR splice variants. Until now, more than 30 distinct AR splice variants have been identified. Among these variants, AR-V7 is the most common one[27–29]. AR-V7 is a truncated androgen-receptor protein, which retains the trans-activating N-terminal domain while lacks the C-terminal ligand-binding domain[28, 30]. It can promote the activation of target genes irrespective of serum androgen levels, leading to the development and growth of prostate cancer. Therefore, the expression of AR-V7 may indicate a poor response and prognosis for ARSi or ADT. Our previous retrospective study indicated that AR-V7 expression in newly diagnosed prostate cancer is intimately correlated with the prognosis and effectiveness of ADT.
Now we focus on AHT. This study aims to report the prognosis of AR-V7 positive patients receiving AHT. AHT after RP may be considered as an effective treatment for patients with high-risk localized and locally advanced prostate cancer in China although it is recommended only for pN + by current EAU Guidelines[32, 33]. Moreover, in China, quite a few patients choose to receive AHT instead of adjuvant radiotherapy because of the fear of complications of radiotherapy.
The AR-V7 positive rates of nmHSPC vary substantially among the different studies[14, 15, 19, 34–36] (range 1.6% from 91.8%), which may because of the differences in the TN stage, ethnicity and antibody. Moreover, our previous study reported that the AR-V7 positive rates of nmHSPC was 11.1%, which is lower than this study (19.1%). The difference may because of inclusion of lower T stage (< T2) and usage of biopsy tissue in previous study. Our results showed that AR-V7 was an independent risk factor for PFS, OS and CSS in high-risk prostate cancer patients who received adjuvant treatment. In subgroup analysis, our results showed AR-V7 status was an independent risk factor for OS and CSS in locally advanced disease, but not the localized disease.
Despite recent medical advances in advanced prostate cancer, the development of systemic adjuvant therapy has remained relatively stagnant over the last few decades for patients with high-risk disease, consisting of only ADT. Novel hormonal therapies may provide oncologists with more efficacious drugs in the adjuvant setting, potentially leading to effective adjuvant therapy options for clinicians treating men with high-risk localized prostate cancer. Some retrospective cohort study demonstrated that adjuvant radiotherapy plus ADT was associated with improved OS compared to ADT alone (HR = 1.5) . For AR-V7-positive prostate cancer patients, a novel therapeutic strategy is needed to improve treatment outcomes. Antonarakis and colleagues demonstrated that taxanes appear to be more efficacious than enzalutamide or abiraterone therapy in AR-V7-positive patients. Furthermore, AR-V7-positive patients may also benefit from drugs which directly target AR-V7, such as ASC-J9, cisplatin, niclosamide, etc.