The Use of Statins Is Related to a Lower PSA Level After Endoscopic Enucleation of the Prostate with Holmium Laser (HoLEP) for the Treatment of BPH- Beyond the Abstract

The treatment of large prostate adenomas is a challenge, and endoscopic enucleation of the prostate with Holmium-Yttrium-Aluminium Garnet laser (HoLEP) has been gaining strength as the enucleation method of choice due to its efficacy and safety.1 Initially described in 1998 by Peter Gilling2 has become more popular in the world in the last ten years, and the number of procedures has increased accordingly.3,4

Some patients undergoing to HoLEP persist with higher levels of prostate-specific antigen (PSA), without necessarily having prostate cancer.5 This phenomenon can confuse urologists and often lead to unnecessary biopsies. Knowledge of factors related to a lower PSA reduction after surgery can help better define the management in these cases. To address this, we sought to identify the clinical factors related to the PSA drop in the postoperative period after HoLEP.6

This study was a retrospective analysis of a prospectively collected database of adult male patients undergoing HoLEP at a single tertiary institution from September 2015 to February 2021. A total of 175 men aged from 49 to 92 years with prostate size ranging from 25cc to 450cc (assessed by transrectal ultrasound) were evaluated. The inclusion criteria were patients with lower urinary tract syndrome (LUTS) resulting from benign prostate hyperplasia (BPH), with surgical indication due to refractoriness, intolerance, or contraindication to combined therapy, and in agreement with the endoscopic enucleation surgical procedure. Exclusion criteria were men with a previous diagnosis of prostate cancer, patients who failed to follow up with post-operative care, and patients who had had an incomplete pre-operative evaluation. Thus, 126 patients were included in the final analysis. All had a moderate to severe (≥12) International Prostate Symptom Score (IPSS). The postoperative evaluations were performed after one week of discharge and between 6 and 8 weeks. After the first year of follow-up, consultations were held annually.

The duration of previous treatment provided with Finasteride was considered in assessing the PSA of patients who used this medication. Patients who had urinary tract infections (UTI) were excluded by clinical examination, urinalysis, and uroculture. Thus, postoperative PSA was collected only in patients free of UTI. All dyslipidemic patients evaluated used Simvastatin 10mg per day as the standard medication provided by the Brazilian public health system.

The mean age of the operated patients was 70.0 years, and 26.19% (33) of the patients use statins, 23.80% (30) are diabetics, and 55.55% (73) are hypertensive. Only 3.9% (5) of the patients used anticoagulants, and 19.94% (24) used platelet antiaggregant.
The mean preoperative PSA value was 6.48 (± 6.61), the mean postoperative PSA 1.14 (± 1.78), and the mean prostate weight was 92.5, ranging from 25g to 450g. The technique adopted in the first 30 cases was the Trilobar, and after overcoming the learning curve, the En-Bloc resection technique was adopted. The catheterization time and hospital stay in our series were 1.3 and 1.2 days, respectively, with a very low incidence of UTI (1.7%).

Post-operative serum PSA values showed a statistically significant correlation with age: patients with PSA lower than 1 ng/ml had a mean age of 71.56 years, while those with postoperative PSA greater than one ng/ml were 68.17 years (p=0.042). Patients with a post-operative PSA value greater than 1 ng/mL were 3.5 times more likely to have a diagnosis of prostate cancer (PCa) in the anatomopathological examination results after HoLEP (p=0.055). All patients diagnosed with PCa were classified as ISUP 1. The multivariate analysis was performed, and the association between statin use and PSA values < 1 ng/mL after surgery was evidenced (hazard ratio [HR]:3.71, 95% CI: 1.18 - 11.59, p=0.024).

This study was the first in the literature to discuss the hypothesis that there may be an association between the use of statins and serum PSA values in the postoperative period of endoscopic enucleations of the prostate. The association between the use of statins as lipid-lowering agents and preoperative serum PSA levels has been studied to elucidate the elusive role of PSA in this specific group of patients. In 2008, Hamilton RJ carried out a longitudinal study with 1.214 men prescribed with statins and evaluated that the PSA value was reduced by 4.1% (P<0.001) after the continued use of statins.7 This medication inhibits 3-hydroxy-3-methylglutal-coenzyme A reductase, which leads to the reduction of cholesterol biosynthesis, essential in the synthesis of androgens, which in turn influences cell signaling towards a decrease in serum PSA production. A second mechanism that may explain this reduction is the anti-inflammatory effect of statins, which also exert this action on the prostate, thus contributing to the reduction in PSA values.

A prospective analysis of patients undergoing HoLEP and a prolonged follow-up period could help obtain more accurate future data. This last aspect is essential for documenting the medium and long-term evolution of postoperative PSA and for confirming that these patients with PSA nadir above 1.0 ng/mL do not harbor foci of malignant neoplasia in the peripheral zone of the prostate.

Written by: Caio V. Suartz, MD, Urologist, Division of Urology, Institute of Cancer of São Paulo (ICESP), University of São Paulo. São Paulo, Brazil

Co-Authors: Natália Doratioto Serrano Faria Braz, Sabrina Thalita dos Reis, Gabriel dos Anjos, William Carlos Nahas, Alberto Azoubel Antunes. Division of Urology, Clinics Hospital, University of São Paulo Medical School, São Paulo, Brazil


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