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Can benign prostatic tissue left after radical prostatectomy cause detectable PSA levels?
Executive Summary
Detectable PSA after radical prostatectomy can arise from multiple causes; evidence shows retained benign prostatic tissue can produce PSA, but the clinical significance and frequency of this effect are contested. Several surgical-pathology cohorts report that benign residual glands rarely generate PSA levels above biochemical-recurrence thresholds, while physiological measurements and clinical guidance note that even tiny amounts of benign tissue can yield low but detectable PSA with ultrasensitive assays [1] [2] [3].
1. How strong is the pathology evidence that benign glands are innocent bystanders?
Surgical-pathology series following men after radical prostatectomy observe that finding benign glandular tissue at margins does not consistently predict PSA recurrence; multiple cohort analyses show very low rates of sustained detectable PSA attributable to benign tissue. A study of 199 patients concluded benign glands at margins did not predict biochemical recurrence [4]. A larger cohort flagged extremely low measurable PSA and biochemical recurrence rates among low‑risk men, concluding retained benign elements are an unlikely source of a clinically meaningful PSA rise [1] [5]. These pathology-driven findings emphasize that while microscopic benign tissue can remain, it rarely produces PSA at levels typically used to define cancer recurrence.
2. Why do some clinicians and guidelines still list residual benign tissue as a cause?
Clinical reviews and guideline-oriented summaries warn that postoperative PSA should be undetectable and list residual benign tissue among several reasons for detectable PSA, alongside local recurrence and metastasis [3]. This stance rests on the biological fact that PSA is produced by benign prostatic epithelium, and measurement sensitivity has increased; ultrasensitive assays detect PSA at much lower thresholds than assays used in older cohorts. Clinical guidance therefore treats residual benign tissue as a plausible explanation for a low but stable detectable PSA, particularly when levels are well below biochemical‑recurrence cutoffs and lack a rising trajectory [3].
3. Quantitative measurements — can tiny amounts of tissue make a measurable PSA?
Physiological measurements estimate PSA production on a per-gram basis for benign prostate tissue, with reported values around 0.3–0.5 ng/mL per gram of tissue, meaning small residual fragments could yield low-level PSA detectable by ultrasensitive tests [2]. Observational studies across larger cohorts, however, observed that measurable postoperative PSA in carefully selected low‑risk groups was exceptionally uncommon, implying that typical retained microscopic foci after meticulous surgery seldom produce clinically relevant PSA signals [1]. The apparent tension reflects differences between theoretical per-gram production, assay sensitivity, and real-world surgical completeness and pathology sampling.
4. What do long-term recurrence statistics tell us about true cancer versus benign causes?
Longitudinal series show that a substantial fraction of men develop biochemical recurrence over a decade, but those recurrences are interpreted as cancer recurrence rather than benign PSA production in most cases because they tend to rise over time and cross standard thresholds like 0.2 ng/mL [6]. Older and larger epidemiologic studies document rising PSA trajectories consistent with cancer biology, whereas cohorts focused on margin benignity report almost no progression attributable solely to benign remnants [4] [5]. Therefore, a solitary low or ultrasensitive detection without subsequent rise is more plausibly explained by benign tissue or assay noise, while a sustained rise points strongly to recurrent malignancy.
5. How should clinicians and patients interpret a detectable PSA after surgery?
Clinical interpretation must combine assay characteristics, trajectory, and clinical context: a single ultrasensitive detectable PSA after radical prostatectomy is not definitive; clinicians use serial measurements and thresholds to distinguish benign residual production or assay variability from true recurrence [2] [3]. When PSA is very low and stable, residual benign tissue is a reasonable explanation supported by pathology cohorts; when PSA rises or exceeds conventional biochemical‑recurrence thresholds, the presumption shifts to recurrent cancer and prompts staging and salvage therapy considerations [1] [6]. This balanced approach aligns the biological fact that benign glands make PSA with cohort data showing such production rarely causes clinically meaningful postoperative PSA levels.