Prognostic value of intraductal carcinoma subtypes and postoperative radiotherapy for localized prostate cancer

Background: Intraductal carcinoma of the prostate cancer (IDC-P), as a specific pathological type in prostate cancer which usually implies a poor prognosis. IDC-P morphology can be divided into two subtypes: Pattern 1, sieve like or loose cribriform structures; Pattern 2, solid or dense cribriform structures. The purpose of the study is to identify the impact of IDC-P and its subtypes on the prognosis of patients undergoing post-operative radiotherapy (PORT) after radical prostatectomy (RP) due to localized prostate cancer(PCa).

Methods: We performed a retrospective study of patients with localized PCa treated by RP followed by PORT or not. Patients with localized PCa who underwent RP from August 2013 to December 2020 were included in this study.

Inclusion criteria: post-operative PSA dropped to less than 0.1 ng/ml after RP, had at least 1 poor prognostic risk factor (including high Gleason's grouping; positive surgical margins; seminal vesicle invasion; extraprostatic extension; and lympho-vascular invasion), and were eligible for adjuvant radiotherapy.; In this study, patients who underwent salvage radiotherapy after RP due to biochemical recurrence (two consecutive PSA > 0.2 ng/ml) were also included, but not patients with persistent postoperative PSA > 0.1 ng/ml.

Exclusion criteria: patients using other types of therapy prior to biochemical recurrence. Screening cases with pathological results of intraductal carcinoma, subtyping was completed by a pathologist, grouped by intraductal carcinoma (+/-; pattern 1/ 2) and treatment regimen (RP + PORT / RP only), Kaplan-Meier curves were plotted based on the time to biochemical recurrence-free and overall survival of the patients, and Cox regression analyses were performed. Finally, based on the results of Cox regression analysis, we initially predicted the probability of biochemical recurrence and death of the patients by plotting the nomogram.

Results: A total of 139 patients were included in this study with a median follow-up of 61.5 months. K-M curves showed that patients with "IDC-P (+) RP only" had the worst prognosis; patients with IDC-P could have a survival benefit after receiving PORT; whereas patients with non-intraductal carcinoma had a better prognosis than the above patients with or without PORT. In addition, patients with IDC-P(+) pattern 2 were more likely to experience biochemical recurrence and death. Multivariate Cox regression analysis showed that pattern 2 was a risk factor for biochemical recurrence and death. Other BCR-related risk factors in the research: Gleason grading group 5 (HR = 3.343, 95% CI: 1.616-6.916, P = 0.001), PM (HR = 2.124, 95% CI: 1.044-4.320,P = 0.038) and PORT (HR = 0.266, 95%CI: 0.109-0.647, P = 0.004). Other OS-related risk factors in the research: Grading group 5 (HR = 3.642, 95%CI:1.475-8.991, P = 0.005), SVI (HR = 2.522, 95% CI: 1.118-5.691, P = 0.026) and PORT (HR = 0.319, 95%CI: 0.107-0.949, P = 0.040).

Conclusion: Patients suffering from localized prostate cancer with IDC-P(+), especially IDC-P pattern 2, are more susceptible to biochemical recurrence and death after radical prostatectomy. While postoperative radiotherapy can alleviate the negative prognostic impact from IDC-P. It is implied that IDC-P can also be an indicator to be considered in PORT decision making to some extent.