The serum PSA determination is the most commonly used method to detect PCa. Usually, the PSA level > 4 ng/ml is considered abnormal. Over the past few decades, a high frequency of PCa patients with a PSA level < 4 ng/ml has been reported . Autopsy studies have shown that there was a high incidence of occult cancer in the prostate of men who die without being diagnosed with PCa . Thus, the incidence of PCa patients with a PSA level < 4 ng/ml may be underestimated at initial diagnosis. Based on a large population analysis, we found that 11.68% of PCa patients were initially diagnosed with a PSA level < 4 ng/ml. Several novel findings have been identified in our study as follows.
First, the 24,054 PCa patients with a PSA level < 4 ng/ml had more favorable clinical characteristics than those with other PSA level(4–10 ng/ml, 10–20 ng/ml and > 20 ng/ml): the patients with a PSA level < 4 ng/ml were younger and diagnosed with lower T stages (T1–2), lower Gleason grades and lower lymph node metastasis rates. This is consistent with contemporary studies [10, 16, 17]. However, in our study, there were more cases in stage M1 among patients with a PSA level < 4 ng/ml compared with those with a PSA level of 4–10 ng/ml. PCa patients with a PSA level < 4 ng/ml should have undergone abnormal digital rectal examination or magnetic resonance imaging , so according to stage, the T1 stage patients comprised the lowest proportion of the patients among the different PSA level groups. Therefore, the PCa patients with a PSA level < 4 ng/ml may be biologically aggressive in some respects, and physicians should appropriately pay attention to prostate patients with a low PSA level. Besides, married patients and Caucasian patients were more likely to have lower PSA values; whereasAfrican-American men without PCa tended to have higher PSA values than Caucasian men without PCa .
Furthermore, several prognostic factors for PCa patients with a PSA level < 4 ng/ml, which were correlated with higher mortality risk, were found, including older age (≥65 years), unmarried status, African-American ethnicity, high T stage (T4), high M stage (M1), higher Gleason grade, and lack of surgery or radiotherapy. Our result suggested that the Gleason grading system had an affirmative predictive value in the prognosis of PCa patients with a PSA level < 4 ng/ml. Initial treatment of diagnosed male patients with PCa requires evaluation of clinical staging based on a digital rectal examination, the pretreatment serum PSA value, the Gleason score of a biopsy and the percentage of cancer involvement in the biopsy core. Though our study showed that patients could benefit fromsurgery and radiotherapy, and active surveillance could be considered as the preferred option for localized low-risk PCa patients [20,21,22,23,24,25]. Based on prognostic factors, the PCa patients with a PSA level < 4 ng/ml can receive a preliminary evaluation from physicians. For PCa patients with a PSA level < 4 ng/ml, risk stratification (high Gleason grade and T stage), age, life expectancy, comorbidities and patient preferences should be considered in the choice of treatment strategies.
To our knowledge, this is the first large-sample-size population-based study focused on PCa patients with a PSA level < 4 ng/ml. Moreover, our study is based on a comprehensive design, including analysis of tumor characteristics, patient treatments, and survival outcomes. However, there were several limitations in our study. First, information on prostate volume, family history, body mass index or biochemical recurrence was not available in the SEER database. Similarly, the information on RT radiation dosage was unavailable. Last but not least, the reasons for such patients to visit doctors were not available. Besides, the data of PSA from SEER database are limited. We will enrich the conclusions drawn in our study through other data sources in future research, and make more comprehensive and in-depth analysis and summary of tumor characteristics, treatments, and survival outcomes for patients with PSA < 4 ng / ml.