Hypothesis / aims of study
Benign prostatic hyperplasia (BPH) is a prevalent condition that affects over 50% of men over the age of 50, often resulting in lower urinary tract symptoms (LUTS) that significantly impact their quality of life [1]. Multiple procedures are available to treat this condition through tissue removal, and as a result, there is a possibility of finding incidental prostate cancer (iPCa), as previous studies demonstrate that autopsy specimens reveal that prostate cancer is present in approximately 40% of men aged 60 or older, and almost 60% of men aged 80 or older. One of the modalities is enucleation procedures of prostate (EEP), which Holmium Laser Enucleation of the Prostate (HoLEP) is the most used technique. This procedure does not only significantly improve urinary flow but also removes a substantial amount of prostate tissue. Therefore, the purpose of this study is to examine clinical factors related to iPCa, as well as low-risk and high-risk prostate cancer, after undergoing HoLEP. The objective is to assess the cancer grade and detect any possible predictive factors associated with the pathology report. Moreover, we intend to comprehend potential impacts that iPCa has in the surgical outcomes, as well as comprehend the management of these patients. By doing so, this investigation will offer valuable insights to clinicians and patients regarding the possibility of iPCa following HoLEP and its effect on the procedure's results. Ultimately, this understanding will aid in counseling patients and enhancing their treatment strategies, leading to superior clinical outcomes.
Study design, materials and methods
We conducted a retrospective chart review of 501 patients who underwent HoLEP performed by a single surgeon at a single institution from July 2017 to August 2022. Patients with a previous diagnosis of prostate cancer (n=54) or prostate radiotherapy (n=1), those without baseline PSA (n=9) or prostate size (n=19), and those without a pathology report (n=1) were excluded from the study. After exclusions, we identified 417 patients who met our inclusion criteria and were divided into three groups based on their pathology report: BPH, low-risk prostate cancer (Gleason grade 1), and high-risk prostate cancer (Gleason grade 2 to 5). We collected pre-operative information including age, race/ethnicity, use of 5 alpha-reductase inhibitors (5αRi), PSA, prostate size, PSA density, and history of negative prostate biopsy. We also collected the prostate resected volume and operative time. Statistical analysis was performed with SPSS version 28 software. Means and standard deviations (±SD) or medians and interquartile ranges [25th-75th] were calculated according to the data distribution. A comparison of numerical variables between groups was performed using the ANOVA or Kruskal-Wallis test as required. Categorical variables were analyzed with a Chi-square test. To evaluate the association between clinical and demographic variables with overall de novo prostate cancer (GG 1 to 5) and clinically significant prostate cancer (GG2 to 5) a multivariable-adjusted logistic regression analysis was performed. A p-value<0.05 was considered statistically significant.
Results
The present study enrolled 417 patients, which mean age was 69.1±8.5 years, 348 (83.5%) were White or Caucasian (%), 199 (47.7%) were on 5α-Reductase inhibitors pre-operatively, and 168 (40.3%) hypertension. Before surgery median PSA was 4.4 [2.2-8.1] ng/m, prostate volume was 102 [74-155], 24 (5.8%) had a PSA density > 0.15, and 156 (37.4%) had a prostate biopsy before HoLEP. The first PSA after HoLEP was 0.40 [0.21-0.78] ng/mL, this was recorded at 3 [2-3] months after the procedure. The study identified 40 (9.6%) with iPCa on histopathological examination (HPE). Among those with prostate cancer, 29 (72.5%) had a Gleason grade (GG) of 1, while 8 (20%) had a GG of 2. Only one patient was found for each of the GG 3, 4, and 5. The BPH group was composed of 377 (90.6%) patients who were categorized into the BPH group, while 29 (7%) were classified as low-risk and 11 (2.6%) as high-risk. On multivariable-adjusted logistic regression analysis neither age, Race/ethnicity, preoperative prostate size, PSA, or prostate biopsy were not associated with de novo diagnosis of prostate cancer (GG 1 to 5) or clinically significant prostate cancer (GG 2 to 5), although hypertension was associated with overall prostate cancer (OR = 4.256, 95% CI: 2.022 - 8.958; p < 0.001) but not to clinically significant prostate cancer. During follow-up after HoLEP the incidence of acute urinary retention was 35 (8.4%), UTI 31 (7.4%), gross hematuria 57 (13.7%), bladder neck stenosis 8 (1.9%), and urethra stricture 9 (2.2%) (Table 2). When analyzing the incidence of complications among groups it was observed that the frequency of urethra stricture was significantly higher in the group of patients with de novo diagnosis of GG1 3 (10.3%) than the rest of the groups (p=0.007).
Interpretation of results
HoLEP is a highly effective size-independent treatment for BPH, providing improved uroflowmetry results and enhancing the quality of life. However, the removal of larger volumes of prostate tissue during the procedure can also reveal information about the presence of neoplasia in the prostate. In our study, prostate cancer was found in nearly 10% of patients undergoing HoLEP, highlighting the importance of informing patients about this possibility. This finding is significant as there was no significant association between PSA and other factors with the detection of prostate cancer in the study population. Therefore, clinicians cannot accurately predict the likelihood of prostate cancer development in these patients.
The study's investigation revealed different Gleason grades. This led to the hypothesis that certain baseline parameters and intraoperative outcomes could be associated with specific GG. However, after conducting multivariable analysis, no significant association was found between high-risk prostate cancer and demographic factors, preoperative PSA, prostate size, or history of negative prostate biopsy.
These findings lead us to orientate patients who wish and need to undergo a laser enucleation, that the possibility of prostate cancer diagnosis is considerable and that features that we could use to predict these findings are not available. However, the study also demonstrates that patients who wish to treat their urinary symptoms and are uncertain of the possibility of prostate cancer, may use this procedure to treat their LUTS and potentially provide a diagnosis of prostate cancer.
Based on our study's results, we advise that patients considering HoLEP should be fully informed that the incidental diagnosis of prostate cancer is relatively common in patients undergoing this procedure, despite the absence of predictors for this occurrence. However, patients should also be made aware of the potential benefits of HoLEP in improving lower urinary tract symptoms and the positive aspect that prostate cancer may be detected incidentally during this procedure.