Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men worldwide. The introduction of prostate-specific antigen (PSA) testing in the late 1980s significantly transformed the landscape of prostate cancer detection, enabling earlier diagnosis and improved management of localized disease. PSA, also referred to as human kallikrein 3, is a serine protease produced predominantly by prostatic luminal epithelial cells. Its organ specificity makes it a useful biomarker for prostate abnormalities; however, its lack of cancer specificity remains a major limitation in clinical application. The elevation of PSA in the bloodstream is generally indicative of a disruption in the normal cellular architecture of the prostate gland. This disruption facilitates the leakage of PSA into the systemic circulation. While prostate cancer is a significant cause of elevated PSA, numerous benign conditions can also result in increased PSA levels. These include benign prostatic hyperplasia (BPH), prostatitis (both acute and chronic), prostatic manipulation (e.g., digital rectal exam or catheterization), prostatic infarction, and urinary retention. Among these, BPH and prostatitis are the most significant benign contributors to elevated PSA and pose a diagnostic challenge in distinguishing malignant from non-malignant causes of PSA elevation. The clinical utility of PSA as a screening tool has been heavily debated due to its low specificity for prostate cancer. PSA screening can lead to overdiagnosis and overtreatment, especially in cases where elevated PSA is due to benign pathology. Despite its limitations, PSA remains widely used in clinical practice, often supplemented with other diagnostic tools such as digital rectal examination (DRE), multiparametric MRI (mpMRI), and, when necessary, transrectal ultrasound (TRUS)-guided biopsy. In practice, when an elevated PSA level is detected, and there are no immediate signs of malignancy on DRE or imaging, clinicians often face a diagnostic dilemma. Currently, there are no established guidelines for performing repeat serum PSA tests in cases of incidental PSA elevations. As a result, management strategies vary, with many urologists relying on clinical experience and institutional protocols. One commonly employed strategy involves the empirical use of antibiotics even in patients without any signs of urinary tract infection or prostatitis. The rationale behind this approach is based on the hypothesis that subclinical or asymptomatic prostatitis may be contributing to the elevated PSA levels. Antibiotic therapy, typically with fluoroquinolones or other agents with good prostatic penetration, is administered over a course of 2–4 weeks. After completion of therapy, PSA levels are reassessed. If a significant decline is observed, this suggests an inflammatory or infectious etiology, and biopsy may be deferred. Conversely, if PSA remains elevated, further evaluation including biopsy is often warranted. Several studies have investigated the efficacy and reliability of using antibiotic therapy to normalize PSA levels and avoid unnecessary biopsies. For example, a study by Serretta et al. (2008) demonstrated that in a cohort of patients with elevated PSA and no clinical symptoms of prostatitis, approximately 36% experienced normalization of PSA levels following a 3-week course of ciprofloxacin, thus avoiding biopsy. However, the study also noted that a portion of these patients had PSA rebound on follow-up, raising concerns about the durability of the response and potential delayed diagnosis of cancer (3). Another investigation by Park et al. 2014 suggested that PSA reduction following antibiotic therapy does not reliably exclude prostate cancer. In their study, although PSA levels decreased significantly in many patients after antibiotic treatment, a substantial proportion of those patients were still found to have prostate cancer upon biopsy. This highlights the importance of not relying solely on PSA normalization as a surrogate for excluding malignancy (5). Despite these concerns, antibiotic treatment in select patient populations remains a valuable tool for refining biopsy decision-making. It is particularly useful in younger patients or those at increased risk for complications from biopsy. Moreover, combining post-antibiotic PSA levels with imaging findings from multiparametric MRI (mpMRI) may enhance diagnostic accuracy. mpMRI has emerged as a critical adjunct in the assessment of elevated PSA, offering improved localization and risk stratification of suspicious lesions using the Prostate Imaging Reporting and Data System (PI-RADS) (6). When PSA levels remain elevated after antibiotic therapy, and mpMRI reveals lesions scored PI-RADS 4 or 5, the probability of clinically significant prostate cancer is high, and biopsy is strongly indicated. Conversely, in patients with normalized PSA and no suspicious findings on mpMRI, biopsy may be safely deferred, reducing patient morbidity and healthcare costs. Correlating biopsy outcomes with mpMRI findings and antibiotic responsiveness thus presents a promising strategy for optimizing prostate cancer screening pathways. In light of this, we propose a study to evaluate the histopathological outcomes of prostate biopsies in patients with elevated PSA, comparing those whose PSA levels normalize following antibiotic treatment to those who do not respond. Additionally, we aim to correlate these outcomes with mpMRI findings to determine whether a combined approach can reliably distinguish benign from malignant causes of PSA elevation. This study may provide evidence to support a more standardized protocol for managing patients with elevated PSA, minimizing unnecessary biopsies without compromising cancer detection rates. In conclusion, while PSA remains an essential tool in prostate cancer screening, its limitations necessitate the use of adjunctive strategies. Empirical antibiotic therapy, followed by PSA reassessment and supplemented with mpMRI, offers a nuanced approach to patient selection for biopsy. Further research, including histopathological correlation, is critical to validate this strategy and refine clinical guidelines. In light of this, we propose a study to determine whether the use of empirical antibiotics results in a reduction in prostate biopsy rates.
AIMS & OBJECTIVES. HYPOTHESIS: Empirical use of antibiotics in patients with elevated PSA leads to decrease in PSA levels, reduced incidence of prostate biopsy and reduced incidence of MRI usage. Aims: To assess the decrease in PSA, need for mp MRI and prostate biopsy by use of antibiotics in patients with elevated PSA PRIMARY OBJECTIVE To determine whether use of antibiotics in patients with elevated PSA leads to decrease in prostate biopsy rates SECONDARY OBJECTIVE Compare the decrease in serum PSA levels between patients receiving antibiotic therapy and those who do not. Assess the histopathological findings of prostate biopsies in patients with elevated PSA, correlating them with the use of antibiotics. To analyse mpMRI findings in study group and control group MATERIALS & METHODS Study design: - This was a prospective, randomized controlled study Institute: The study was conducted at the All-India Institute of Medical Sciences, Bhopal, in the Department of Urology. (August 2023- March 2025). Conflict of interest: Nothing to disclose. Ethical Clearance: Ethical clearance was obtained from the Institutional Human Ethics Committee (IHEC)- Student Research of AIIMS Bhopal. Ref no - AIIMS/BPL/IECSR/JAN/23/SS/01. Dated :24/08/2023 Study population -This is a prospective study to be conducted from July 2025 to Dec 2025 on patients presenting with LUTS with elevated serum PSA levels in Urology OPD after issue of letter of permission according to the inclusion and exclusion criteria. The patients will be given the informed consent sheet and patient information sheet. Inclusion Criteria - Age >/=45 years and <80 years - Male patients presenting with LUTS with elevated Serum PSA levels>/= 4ng/ml Exclusion Criteria - Documented prostate cancer or any other malignancy - Documented metastatic disease - Patients with hard nodule on DRE - Patients with documented Urolithiasis. - Patients with history of recurrent Urinary Tract Infection - Patients with documented urethral stricture disease - Patients with history of any prostate surgery in last 2 years - Patients who do not consent to participate in study Study duration: 18 Months Sample size- We have calculated sample size using g-power software with power at 80% and alpha error at 5% based on a reference article data. The calculated sample size is 102 per group. Assuming non-responders of 10%, final size will be 110 per group, which is 220 participants in total. But since we have limited time duration for this study, we will include all the participants that enrol during this study period with minimum of 20 participants in each group. Randomisation technique- Participants allocated to the study group (antibiotic) or control group (non-antibiotic) using computer-generated block randomization. A random sequence created using a computerized random number generator to ensure equal allocation while maintaining concealment. This method will minimize selection bias and ensured balanced group sizes throughout the enrollment process.
Blinding- This study conducted using a double-blind design. Both the participants and the outcome assessors blinded to group allocation to minimize performance and detection bias. Participants not informed whether they had been assigned to the study group (receiving antibiotics) or the control group (receiving no antibiotics), as both arms received identical instructions and follow-up protocols. Investigators performing PSA testing, mpMRI interpretation, and histopathological evaluations similarly blinded to treatment allocation.Intervention – The study group will be advised to take antibiotic medication for 3 weeks. Preferred agents included fluroquilonones like Tablet. Levofloxacin 500 mg od. This antibiotic medication to be modified according to antibiotic sensitivity in urine culture (if any growth noted) and according to creatinine clearance of the patient if there was any renal impairment. After 3 weeks, patient asked to give blood sample for repeat serum PSA levels and then underwent mpMRI, followed by prostate biopsy done according to EUA guidelines either by transperineal or transrectal route. The biopsy sample then processed and examined. The control group kept on observation and not be given antibiotic medications, but will undergo identical monitoring and assessment. Repeat serum PSA sampling was done after 3 weeks followed by mpMRI and further underwent Prostate biopsy according to EUA guidelines.
This study will be conducted in the department of Urology AIIMS Bhopal on patients presenting with LUTS and elevated serum PSA levels and patients were included in this study according to inclusion exclusion criteria. Consent taken before including the patient in the study. Patient information sheet provided. History and physical examination done on all patients. Patients will be investigated according to AIIMS protocol. Investigations on first visit included Complete blood count, renal function tests, liver function test, INR, viral markers, urine routine microscopy and culture with antibiotic sensitivity. Initial value of serum PSA will be noted at first visit Radiological investigation on first visit will include Ultrasonography of Kidney, Ureter, Bladder with post void residual (USG KUB with post void residual) findings After taking basic history, examination and investigations, selected participants to be randomized into study group and control group. The study group advised to take antibiotic medication for 3 weeks. Preferred agents included fluroquinolones like Tablet. Levofloxacin 500 mg od. This antibiotic medication was modified according to antibiotic sensitivity in urine culture (if any growth noted) and according to creatinine clearance of the patient if there was any renal impairment. After 3 weeks, patient asked to give blood sample for repeat serum PSA levels and then goes for mpMRI which is done in Radiology department in AIIMS Bhopal followed by prostate biopsy done at modular OT complex by Urology Department, either by transperineal or transrectal route. The biopsy sample then processed and examined by Department of Pathology and Lab Medicine of AIIMS Bhopal. The control group to be kept on observation and not be given antibiotic medications and directly repeat serum PSA sampling was done after 3 weeks followed by mpMRI and further Prostate biopsy according to EUA guidelines. Once prostate biopsy report is obtained, the results will bw evaluated and statistical analysis will be done. |