From the Guidelines
The next step in management for a 53-year-old male with rising PSA levels despite a negative initial prostate biopsy and absence of high-grade PI-RADS lesions would be to perform a repeat prostate biopsy, preferably using an extended or saturation biopsy technique. This approach should include standard systematic sampling plus additional cores (typically 20-24 cores total) to increase detection sensitivity. Prior to the repeat biopsy, obtaining a multiparametric MRI (if not already done) would be valuable to guide targeted sampling of any suspicious areas, even those with lower PI-RADS scores. The timing of this repeat biopsy should generally be within 6-12 months of the initial negative biopsy if PSA continues to rise or PSA velocity exceeds 0.75 ng/mL/year, as suggested by studies such as 1. Additionally, incorporating biomarker tests such as the Prostate Health Index (PHI), 4Kscore, or SelectMDx before proceeding with repeat biopsy can help stratify the patient's risk and potentially avoid unnecessary procedures, as noted in 1. These recommendations are based on the understanding that rising PSA levels suggest ongoing prostatic pathology that may have been missed on initial sampling, and that approximately 20-30% of men with initially negative biopsies but persistent PSA elevations will be diagnosed with prostate cancer on subsequent evaluation, as discussed in 1.
Some key points to consider in this management plan include:
- The use of biomarkers to improve the specificity of detection and guide the decision for repeat biopsy, as mentioned in 1.
- The role of multiparametric MRI in identifying regions of cancer missed on prior biopsies, as suggested in 1.
- The importance of considering the patient's overall risk profile, including factors such as family history and PSA velocity, in determining the timing and approach to repeat biopsy, as discussed in 1.
By following this approach, clinicians can optimize the detection of prostate cancer in men with rising PSA levels despite initial negative biopsies, while also minimizing unnecessary procedures and improving patient outcomes.
From the Research
Next Steps in Management
If the 53-year-old male's Prostate-Specific Antigen (PSA) levels start trending up despite initial negative prostate biopsy and absence of high-grade Prostate Imaging-Reporting and Data System (PIRAD) lesions, the following steps can be considered:
- Close surveillance of PSA levels, with repeat PSA testing at regular intervals, such as every 3 months, as recommended by 2
- Consideration of additional diagnostic tests, such as magnetic resonance imaging (MRI) or template-guided biopsy, to rule out undiagnosed cancer, as proposed by 3
- Evaluation of the patient's risk factors, such as family history, age, and digital rectal examination findings, to determine the need for further investigation or treatment, as suggested by 4
- Discussion of the potential benefits and harms of prostate cancer screening and treatment, including the risk of overdiagnosis and overtreatment, as highlighted by 5
Diagnostic Considerations
In the presence of a rising PSA after a negative biopsy, a low threshold for repeat biopsy should be entertained, as recommended by 3. Saturation biopsy may increase cancer detection, especially in patients with more than two prior biopsies. Adjuncts to improve cancer detection, such as administration of 5-α-reductase inhibitors and MRI, are promising, as noted by 4 and 3.
Treatment Options
If prostate cancer is diagnosed, treatment options will depend on the stage and grade of the cancer, as well as the patient's overall health and preferences. Active surveillance may be considered for patients with low-risk disease, as discussed by 6. However, if the cancer is more aggressive or the patient's PSA levels continue to rise, more definitive treatment, such as surgery or radiation therapy, may be necessary.