HIGH RISK PROSTATE CANCER: COMPARISON OF RADICAL PROSTATECTOMY VERSUS RADIATION THERAPY: EXPERIENCE OF MILITARY HOSPITAL RABAT

Context : To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. Objective: to evaluate overall survival (OS) and relapse free survival of high risk prostate cancer (PCa) treated either with external beam radiotherapy (EBRT) associated with androgen deprivation therapy (ADT) or radical prostatectomy (RP) with adjuvant or salvage radiotherapy and ADT. Also, it is very interesting to compare different acute and late toxicity of the both approach. had benefited from treatment with EBRT with ADT were selected from the other patients by a 1: 2 matching method who will represent the reference group (Group II) to allow a comparison with the experimental arm with the minimum possible bias. Results: The overall survival (OS) at 5 and 10 years was 100 % in the both arms while relapse free survival at 5 years was 91,7 % and 93,1% respectively in group I and II and at 10 years 91,7% in the group multimodal approach and 88,9 % in the EBRT+ADT group without any significant difference. We note more toxicities in the surgical group with more urinary incontinence (p=0,001) and more erectile dysfunction. Conclusion : RP with adjuvant EBRT and EBRT+ADT provided similar long-term cancer control for patients with high-risk prostate cancer but with different toxicity profiles.


Materials and Methods:-
This is a retrospective study comparing two therapeutic modalities in patients with highriskprostateadenocarcinoma: EBRT associated to ADT versus surgery followed by radiotherapy "multimodal treatment".
During a period of 10 years from April 2009 and December 2018, 149 patients with high-risk prostate cancer were admitted to the radiotherapy department of the Mohammed V military hospital in Rabat (HMIMV). Seventeenpatients(Group I) underwentradical prostatectomy with pelvic lymphadenectomy. EBRT in association with LH-RH analogues was indicated in patients with adverse features (positive margins, T3, post-operative detectable PSA, high grade).EBRT was delivered in 32 -33 fractions with a total dose of 64 -66 Gray using volumetric modulated arctherapy technique VMAT to prostate fossa. Thirty four patients(Group II) with a ratio 2:1 were selected in the basis of clinical features (similar to group I) and treated with EBRT with long course ADT. EBRT was delivered to pelvis with a total dose of 46 -50 Gy with a boost to prostate of 24 -26 Gy using VMAT.
Statistical analysis of the data was performed by IBM SPSS 26 software. Propensity-score matching was performed. Kaplan-Meier survival analysis was used to compare overall survival and free failure survival. Univariate and Multivariate analysis was used.

Patient's Characteristics
The frequency of multimodal approach in our series is 11, 4%. The epidemiological, clinical, paraclinical, and histological characteristics can be summarized in Table 1   Surgery in Group I patients consisted of radical prostatectomy associated with lymph node dissection in 82.4% and radical prostatectomy alone in 17,6 %. Histopathological data on the operative part showed that the gleason score was greater than that found on the biopsy since an ISUP 4/5 was noted in 23.5% versus 17.6%, The surgical margins were reached in 70.6 %, capsular breach was found in 17.6%, the seminal vesicles were affected in 29.4% and perineural sheath was noted in 41.2%. As for lymph node dissection, lymph node involvement was found in 14.3% of patients.

Oncological Outcomes
The overall survival (OS) at 5 and 10 years was 100 % in the both arms while relapse free survival at 5 years was 91,7 % and 93,1% respectively in group I and II and at 10 years 91,7% in the group multimodal approach and 88,9 % in the EBRT+ADT group without any significant difference us shown in the survival curves (figure 1) Non Oncological Outcomes Regarding toxicity after surgical treatment with adjuvant radiotherapy and EBRT-ADT, no statistically significant difference was noted concerning acute toxicity us shown in Table 5 while more late complications was noted in the group treated with combining surgery and EBRT-ADT with a p=0,001 for urinary incontinence and a p=0,027 which tends toward a significance concerning erectile dysfunction ( arms like results of our study since there was no statistically significant difference in 5 and 10 years survival as well as free failure survival between the two therapeutic groups. In the literature, there is many metaanalysis with divergent results, like this one [9] published on 2014 including 17 series showing benefice of RP versus EBRT concerning specific and overall survival but an equivalent biochemical free survival between the two groups. Also, a Swedish metaanalysis of observational studies between 1996 and 2010 [10] with an advantage for RP in patients with good general conditions. In fact, several of the meta-analyses of observational studies available demonstrate robust and statistically significant OS and SS benefits in favor of RP over RT-based approaches in all clinically localized disease [11,12,13,14]. Indeed, there is a lack of true randomized trial comparing the two treatment modality in a homogeneous high risk population. Through our literature review, in this comparative study [15], long term outcomes appear similar among patients with high risk and very high risk prostate cancer deemed eligible for either RP or EBRT+ADT with similar local recurrence, distant metastasis failure and overall survival.Beyond this, there is equipoise regarding the optimal treatment. Inference must still be drawn from retrospective single-institution studies, population-based studies, and multi-institutional registries, all of which contain inherent selection bias, limited reporting, and potential residual con-founding errors, which are difficult to address even with the best propensity score, instrumental variable, or regression methods and the challenge faced when assembling evidence regarding surgical or radiation-based treatment efficacy for high-risk prostate cancer is the lack of randomized trials to provide sufficient power , the risk of urinary incontinence fell from 2.8 % to 6.5% urethral stenosis from 9.5% to 17.8%. Similarly, in the EORTC and ARO trials, the grade 2 or 3 risk is significantly increased [21]. A partial analysis in the EROTC trial did not show difference in postoperative incontinence [22]. In summary, our study is notdevoidof limitations. First, it includes patients treated with RP over a relatively long period of time. Because surgery has been considered as possible a possible first time treatment for selected high risk prostate cancer only in more recent years at our institution, the effective of patients in surgical arm is very low. Also, because most prostate deaths can occur over 10 years after initial treatment, further follow up is needed to provide more robust estimations of prostate cancer specific survival in both arms.

Conclusion:-
RP with adjuvant EBRT and EBRT+ADT provided similar long-term cancer control for patients with high-risk prostate cancer but with different toxicity profiles. No prospective data is available until now but the the ongoing randomized SPCG-15 trial will provide us with valuable information on this matter.