Overexpression of CXCR7 is a Novel Indicator for Enzalutamide Resistance in Castration-Resistant Prostate Cancer Patients.

BACKGROUND: To evaluate whether the overexpression of chemokine receptor-7 (CXCR7) in prostatic tissues obtained from men with Castration-Resistant Prostate Cancer (CRPC) is associated with resistance to enzalutamide (Enza). METHODS: Based on the inclusion criteria of CRPC in EAU guidelines, all eligible patients treated in our hospital from January 2015 to December 2019 were included. Cases underwent radical prostatectomy, docetaxel-based chemotherapy, or new endocrine therapies (including Enza or abiraterone), and cases with severe cardiopulmonary disease or other malignant tumors were excluded. After immunohistochemical staining for CXCR7 expression in prostatic biopsy tissues, all enrolled cases were divided into two groups, namely, the CXCR7-positive group and the CXCR7-negative group. And then, PSA response to Enza treatment was recorded in detail and comparatively analyzed. In addition, the Cox proportional hazard modeling and the Kaplan-Meier analysis were used to determine PSA progression-free survival (PSAP-FS) and clinical or radiographic progression-free survival (CRP-FS) in this cohort. RESULTS: A total of 79 CRPC individuals were enrolled and evaluated in this study. Median follow-up durations were 24 months (range, 12-42) in the CXCR7-positive group (n = 47) and 28.5 months (range, 12-42) in the CXCR7-negative group (n = 32). The patients with lower CXCR7 expression showed much better PSA response to Enza treatment. There was 84.4% of CXCR7- cases showing decreasing PSA response, while there were 71.4% in the CXCR7/1+ group and 31.2% in the CXCR7/2+ group, respectively. All patients in the CXCR7/3+ group showed increasing PSA response to Enza treatment. And the percentage of patients whose PSA decreased over 50% is significantly higher in the CXCR7-negative group than in the CXCR7-positive group (68.8% vs. 8.5%, P < 0.001), and the percentage of patients whose PSA decreased over 90% is also remarkably higher in the CXCR7-negative group (43.8% vs. 0, P < 0.001). The Kaplan-Meier analysis demonstrated that the oncologic outcomes of CXCR7-negative patients were improved much significantly by Enza treatment in comparison with those of CXCR7-positive patients. Significantly increased median PSAP-FS (21 months vs. 6 months, P < 0.0001) and CRP-FS (27 months vs. 9 months, P < 0.0001) were obtained in the CXCR7-negative group. The further stratified analysis in all CXCR7-positive patients demonstrated that the patients with higher CXCR7 expression showed much worse outcome. The median time of PSAP-FS was 21 months in the CXCR7/1+ group, 9 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, while the median time of CRP-FS was 21 months in the CXCR7/1+ group, 12 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, respectively. CONCLUSION: Overexpression of CXCR7 induced by an AR antagonist in CRPC patients displays much better treatment response to Enza. CXCR7 might be a novel therapeutic target gene for CRPC patients.

[Primary smooth muscle tumor in the male reproductive system: a report of 5 cases and review of the literature].

OBJECTIVE: To systematically study the clinical diagnosis and treatment of smooth muscle tumor in the male reproductive system. METHODS: We analyzed the ultrasonographic features, pathological findings, treatment strategies and postoperative follow-up results of 5 male patients with smooth muscle tumor in the reproductive system, and reviewed other relevant literature. RESULTS: Compared with leiomyoma, leiomyosarcoma exhibited stronger mixed echoes than the testis at ultrasonography, typical mitotic phase (> or = 2/10 HP) of tumor cells at HE staining, and significant expressions of HIF-1alpha and Glut-1 at immunohistochemistry. No relapse was observed in the 2 cases of leiomyoma during the 10-year follow-up after simple tumor resection, nor were recurrence and metastasis in another 3 cases of leiomyosarcoma during the first year after radical surgery without combined radio- and chemo-therapy. CONCLUSION: Primary smooth muscle tumor of the male reproductive system is difficult to be diagnosed. Ultrasonography can help to preliminarily screen leiomyosarcoma. For those with possible leiomyosarcoma, preoperative MRI and intraoperative frozen sectioning examinations are recommended for the possibility of lymphatic metastasis. Postoperative radiotherapy and chemotherapy should be chosen cautiously for those confirmed with leiomyosarcoma by pathological examination.

[Impact of neoadjuvant hormonal therapy on the permanent ¹²5I-seed brachytherapy for localized high-risk prostate cancer].

OBJECTIVE: To evaluate the impact of neoadjuvant hormonal therapy on the permanent transperineal (125)I-seed brachytherapy for localized high-risk prostate cancer. METHODS: Ten patients with T(1)-T(2a) localized high-risk prostate cancer were reviewed. The mean level of PSA was (29.4 ± 12.6) µg/L (20 - 50 µg/L) and the mean prostate volume (54 ± 33) ml. All cases were sequentially treated on a neoadjuvant hormonal therapy with 1 week of Casodex (50 mg/d) and 3 - 10 months (median: 6 months) of Casodex (50 mg/d) with Zoladex (3.6 mg per 4 weeks, SC). Then all patients received the transperineal permanent interstitial (125)I-seed implantation brachytherapy by template method. The matched peripheral dose of seed implantation was 145 Gy (median number of (125)I seeds: 46), urethral peripheral dose ≤ 80 Gy and rectal peripheral dose ≤ 60 Gy. The mean operative duration was 1.75 hours (range: 1 - 2.5 hours). RESULTS: After neoadjuvant hormonal therapy for 3 - 10 months, the PSA level decreased to (1.4 ± 0.7) µg/L in all patients. The mean prostate volume significantly decreased to (25 ± 10) ml (t-test, P < 0.01). The Foley tube extracted at Days 3 - 5 post-brachytherapy. Side effects of mild dysuria (n = 1) and urethral irritation (n = 1) were effectively managed by symptomatic treatment. After a median follow-up of 13 months (range: 3 - 24), the PSA level was (0.9 ± 0.7) µg/L. CONCLUSION: A combination of neoadjuvant hormonal therapy with brachytherapy may lower the PSA level and shrink the prostate volume so as to ensure an effective dose in the target tumor and improve the therapeutic efficacy for localized high-risk prostate cancer.