This large-scale analysis of contemporary incidental PCa patients revealed several noteworthy observations. Those can be summarized as follows.
First, among 344,031 newly diagnosed non-metastatic PCa patients between 2004 and 2015, 5,155 (1.5%) harbored incidental PCa. This observation indicates the rare occurrence of incidental prostate cancer in the US. Indeed, recent studies addressing this entity of PCa are based on relatively small patient cohorts that ranged from 74 to 210 patients.[6–9] A recent (2021) meta-analysis on incidence, predictive factors, as well as oncological outcomes of incidental PCa by Cheng et al. that included 55 studies, resulted in a total of 2,327 incidental PCa patients.[10] This combined number, represents less than half of the current study population. Moreover, none of the previous studies that addressed incidental PCa in a structed fashion from diagnosis to treatment were based on North American patient populations. Taken together, the above points indicate that the current study addresses a knowledge gap regarding incidental PCa that is particularly applicable to North American men, for whom virtually no data exists. Large-scale epidemiologic databases such as SEER or the National Cancer Database (NCDB) are ideal to effectively address incidental PCa, as is shown by the elevated numbers of observations in the current study relative to even a meta-analysis that relies on 55 combined studies.
Second, the rate of incidental PCa increased significantly (p = 0.02) over time (1.9% in 2004 to 2.5% in 2015). Unfortunately, these rates cannot be compared to other studies, examining the rate of incidental PCa over time, in either the United States or any other region, since no large-scale epidemiologic studies similar to the current one, have been reported. Some investigators attempted to address the question regarding annual rates of incidental PCa using substantially smaller cohorts. For example, Capogrosso et al. assessed the rates of annual incidental PCa diagnoses in a European academic center, relying on a total of 74 incidental PCa patients diagnosed between 2007–2016. [7] In their study, an increased rate of incidental PCa over time was observed even if it relied on very small numbers of observations. Similar results were shown by Lin et al, assessing the rate of incidental PCa in a single institution in China. In their report (n = 87), the rate of incidental PCa was also increasing over time. [11] Despite the limited number of observations, these two studies suggest an increase in the proportion of patients with incidental PCa in both European and Asian populations. Indeed, our data suggests that the proportion of incidental PCa patients is also increasing in the United States. It has been hypothesized that this increase may be attributed to the relatively low sensitivity of prostate MRI in the detection of low-grade PCa, as well as a more conservative attitude regarding biopsy.[12, 13] Future studies, relying on similar large scare databases should ideally validate or refute the current study’s findings.
Third, we made important observations when age, PSA values and Gleason score data were tabulated in incidental PCa patients. For example, 11% of all incidental PCa patients harbored GS ≥ 8. Of these GS ≥ 8 patients, the majority were aged less than 80 years. These observations indicate that only a small minority (11%) of incidental PCa patients harbor biologically aggressive PCa (GS ≥ 8). However, most of GS ≥ 8 incidental PCa patients were aged below 80 years. In consequence, incidental PCa with aggressive Gleason score (GS ≥ 8) is very rare, but is not limited to octogenarian patients. Ideally, all GS ≥ 8 patients would have not escaped initial detection prior to TURP. Conversely, incidental PCa patients who harbored GS 6 accounted for the vast majority (64%) of all such individuals. Expectedly, the majority of such patients were also aged below 80 years. Furthermore, the majority (56%) of incidental PCa patients displayed PSA values < 4ng/ml at diagnosis and only a minority had highly elevated PSA values (> 10 ng/ml). Finally, of those incidental PCa patients with PSA > 10 ng/ml, only a minority (27%) harbored GS ≥ 8. Unfortunately, these observations cannot be directly compared with any other series addressing incidental PCa, since insufficient numbers of patients precluded meaningful tabulations such as the current one.
Third, we made important observations regarding treatment rates in incidental PCa patients. Specifically, of all incidental PCa patients, 71% underwent NLT vs. 16% RP vs. 14% RT. The rates of NLT increased significantly (69 to 81%) over time (2004 and 2015). Conversely, the rates of RP and RT decreased (RP: 17 to 10%; RT: 14 to 9%). Since we are the first to report annual treatment rates in incidental PCa in the US, our findings can unfortunately not be compared to other reports. However, the increasing rate of NLT in incidental PCa patients is consistent with current management guidelines for incidental PCa, that recommend NLT in GS 6, as well as select GS 7 incidental PCa patients. [14] In that light, it is noteworthy that the majority of GS ≥ 8 incidental PCa patients underwent NLT. Such management is inconsistent with current management recommendations. It can be postulated, that in these individuals, high age or certain comorbidities prohibited active treatment in the form of RP or RT.
Finally, specific CSM-free survival patterns in incidental PCa patients were also identified. First, in GS 6 incidental PCa patients, six-year CSM-free survival was excellent, regardless of treatment type and PSA values at diagnosis (95–100%). Very similar survival rates were recorded in patients who harbored GS 7 (87–99%). Conversely, in GS ≥ 8 patients, six-year CSM-free survival rates were substantially less favourable (54–92%), especially when NLT represented the subsequent treatment type (54–61%). In GS ≥ 8 patients that were treated with either RP or RT, six-year CSM-free survival rates were higher (79–92% for RP; 72–77% for RT). Taken together, our observations indicate, that in incidental PCa patients that harbor GS ≥ 8, active treatment in the form of RP or RT should be favoured since CSM-free rates significantly exceed those in NLT. This recommendation is consistent with current guidelines. [14]
In summary, incidental PCa in the US is rare. However, the proportion of incidental PCa has been increasing within the last decade. The majority of incidental PCa patients harbor GS 6, PSA values at diagnosis < 10ng/ml and are aged below 80. Most incidental PCa patients undergo NLT, und enjoy very favourable survival. The exception consists of incidental PCa patients with GS ≥ 8 that undergo NLT. In those individuals, active treatment (RP or RT) should be the preferred choice of subsequent treatment.
Despite the novelty of our observations, several limitations need to be acknowledged. First, our study shares limitations of all similar studies that were based on the SEER database and relied on a retrospective data design. Second, the SEER database does not offer information regarding rates of confirmatory biopsy after BPH surgery. Similarly, it does not offer information on preoperative prostate volume. These limitations need to be considered when interpretating the results of our study. Third, the distinction between active surveillance or watchful-waiting cannot be made according to SEER data. In consequence only NLT can be used as a treatment type variable. It can be postulated that the majority of patients in the NLT group were included in either one of these non-local treatment modalities.