Positive Surgical Margins (PSM) after Open Retropubic Radical Prostatectomy: Evaluation of Patient Survival ()
1. Introduction
Prostate cancer is leading cancer in older men and the second leading cause of death (after lung cancer). It is the fourth leading cause of death due to cancer in the general population [1]. In Africa, prostate cancer is diagnosed primarily at locally advanced or metastatic stage [2]. In Senegal, most prostate cancers are diagnosed in locally advanced or metastatic stage [3]. Radical prostatectomy (RP) is a surgical treatment of prostate cancer in which the prostate and seminal vesicles are removed [4]. The oncological principles of cancer surgery advocate the complete removal of cancer with negative surgical margins. In localized prostate cancer, the management of the positive surgical margin (PSM) after radical prostatectomy remains controversial [5] [6]. Positive margins after total prostatectomy are a common pathological situation (10% - 40%) in the daily practice of urologists dealing with prostate cancer. The presence of positive margins correlates with the presence of residual tumor in about 50% of cases [7]. A positive surgical margin (PSM) is defined as the presence of cancerous tissue in contact with the inked borders of the prostatectomy specimen [8]. In our regions, there is no study interested in PSM. The aim of this study was to report the epidemiological, clinical and therapeutic aspects of PSM after radical prostatectomy and to evaluate the follow-up of patients.
2. Patients and Methods
This was a single-center retrospective descriptive study of patients who underwent radical prostatectomy (RP) between 1 June 2004 and 31 December 2019 in Urology-Andrology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected data from the medical records and registers of patients. All patients who had (RP) with invaded surgical margins on pathology report were included. A positive surgical margin (PSM) was defined as the presence of cancerous tissue in contact with the inked borders of the prostatectomy specimen. Patients who had RP with margins status not specified on the pathology report, patients who had invaded margins and were lost to follow-up, and patients with unexploitable records were not included. The parameters studied were age, initial PSA, Gleason and ISUP scores, cTNM and pTNM stages, operative technique, PSA levels after prostatectomy, adjuvant therapy and patient survival. Excel 2013 software was used for statistical analysis and survival was calculated according to Kaplan Meier.
3. Results
During the study period 86 radical prostatectomies were performed. PSM was found in 23 patients (26.7%). The mean age of the patients was 63.7 ± 6.1 years (54 - 74 years). The mean preoperative total PSA level was 31.5 (6.31 - 146 ng/mL). The prostate biopsy showed only prostatic adenocarcinoma. The ISUP 1 group was predominant in our series with 15 patients. Magnetic Resonance Imaging (MRI), Thoracic-abdominal-pelvic Computer Tomography (CT) and scintigraphy was performed to assess the extension of the disease. The prostate cancers were found at the localized stage in 12 patients and locally advanced in 11 patients. A classification adjustment was obtained after pathological examination of the surgical specimen. T-stage was underestimated in 12 patients. All patients who had cancers classified as intermediate risk of recurrence according to D’Amico’s classification were finally at high risk of recurrence (Table 1).
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Table 1. Classification of cancers (TNM and ISUP).
Treatment was open radical retropubic prostatectomy. After RP, the PSA level was undetectable (<0.1 ng/mL) in 4 patients over 4 - 6 weeks. After recurrence all patients who were consenting had hormone therapy. Hormone therapy was medical with Goserelin and Triptorelin (7 patients) or surgical with bilateral testicular pulpectomy (1 patient). A response to hormone therapy was obtained in 05 patients and in 08 patients we noted progression.
The mean overall survival (OS) of the patients in the series was 28.1 ± 34 months. The overall survival of the series at 12 months; 24 months and 36 months was 69%; 65% and 30% respectively (Figure 1). The mean biological recurrence-free survival in the series was 25.7 ± 23 months. Biological recurrence-free survival at 12 months; 24 months and 36 months was 80%; 66%; 60% and 20% respectively (Figure 2).
4. Discussion
Positive surgical margins in men undergoing radical prostatectomy for prostate cancer are a common situation. According to Wright [9] PSM were reported in 21.2% of cases and were more common in pT3a than pT2 tumors and higher-grade tumors. We found a rate of 26.7% PSM. Data from the literature reported rates ranging from 16% to 47% [10] for series contemporary with ours.
In our context, the incidence of PCM may be related to the difficulty of radical prostatectomy in high-risk cancers but also to the locally advanced stage of the cancer in 91.3% of our patients (n = 21). Depending on the stage, there is an increase in PSM rate. For stages T1a, from 0% to 21%, for stages T1b from 30% to 35% [11] For T2 stages, the figures range from 9% for T2a, 24% for T2b and 40% for T2c in Rosen’s series [12]. In the Mayo Clinic series [13], there were 30 and
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Figure 1. Overall survival curve (months).
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Figure 2. Biological recurrence-free survival curve (months).
60% margins for T1 and T2. Moreover, a statistically significant interaction was found between surgical margin status and Gleason score 7 to 10 (P < 0.008) and lymph node invasion (P < 0.001).
The mean pre-therapeutic PSA level was 31.5 ng/mL. The relationship between pre-treatment PSA and positive surgical margins is known. Indeed, Gomez and Shelfo have reported a correlation between PSA and PSM levels [14] [15].
Retropubic radical prostatectomy was performed in all our patients. Bladder neck preservation was not specified in the surgical report. According to Arroua [16] bladder neck preservation does not increase the risk of a PSM. In fact, more than 70% of their patients had early postoperative continence without increasing the number of positive surgical margins.
There is no consensus regarding the optimal management of PSM after total prostatectomy. Treatment options include surveillance, adjuvant radiotherapy and/or hormone therapy or salvage management at biological recurrence [17].
Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins [6].
After recurrence all patients who were consenting received hormone therapy because hormone therapy was the main option to be offered to patients. We noted a response to hormone therapy in 5 patients and progression in 8 patients.
In our study then margins location were not specified. The effect on biochemical recurrence was influenced by the site of the surgical margin, with a posterolateral location having the most significant effect on prognosis [18]. Aydin et al. [19] have shown that the presence of surgical margins at the cervix increases the risk of biologic recurrence more than for any other location.
According to Wright [10] PSM in men undergoing radical prostatectomy for prostate cancer are associated with an increased risk of biochemical recurrence.
The 7-year disease specific survival rates for those at highest risk for prostate cancer specific mortality (higher grade pT3a) were 97.6% for cases with negative surgical margins and 92.4% for those with positive surgical margins.
Overall survival and biological recurrence-free survival in our patients were low compared to data in the literature. This can be explained by the high rate of high risk of recurrence and locally advanced tumor in our series.
The limitation of this study is that it is a small series, we did not explore the factors that affect the prevalence of the PSM such as the surgical approach, the experience of the surgeon, and the tumor status and their localization in the prostate specimen are not specified.
5. Conclusion
Positive margins after total prostatectomy are a relatively common pathological situation in our daily practice of urologists dealing with prostate cancer. The status of the surgical margins as well as their situation in the event of positivity must be specified in the histology reports. Their presence should lead to a search for a biological recurrence in order to offer patients adequate treatment. Standard hormone therapy and radiotherapy are the therapeutic means available in our regions and they offer less survival to patients.