Reported incidence of no residual cancer on RPs ranges from 0.07 to 4.2% (1–11, 20). It is higher after neoadjuvant hormonal treatment [
16].
There are multiple reasons why cancer may not be found on RP after a positive biopsy. In some cases, the cancer may be minute and completely removed by the initial procedure, either needle biopsy or transurethral resection of prostate. Small cancers may be removed from the RP during the technical preparation of the specimen, such as leveling of the paraffin blocks. Small cancer foci can also be completely obscured if the patient has undergone antiandrogen therapy or the RP shows extensive inflammation or granulomatous inflammation. Other reasons include false-positive diagnosis on the initial biopsy, resulting in cancer overdiagnosis, or false-negative diagnosis rendered on the RP. Review of the material by a second pathologist or a specialist in urological pathology can often resolve the latter scenario. Lastly, errors may occur either before a specimen is submitted for pathological assessment or in the pathology laboratory. These errors include switching of patients’ requisitions, mislabelling or switching of specimen containers, mislabelling or switching slides or blocks and information system errors (e.g. incorrect case entry in the information system or mixed accession numbers) [
28].
In our study, the incidence of RPs with no residual cancer after an initial routine examination of the 1,328 specimens was 0.6%. This figure includes both untreated and hormonally treated patients. The incidence was 0.2 and 0.4%, respectively, of the total number of RPs included in the study, or 0.4% (3 out 700 untreated patients) and 0.8% (5 out 628 treated patients) when the two groups were considered separately. The former is well in the range of values reported in the literature for untreated patients and very close to the figure published by Herkommer et al. [
11,
13]. The latter value seen in our treated patients is much lower than that observed by Kollermann et al. [
16].
Additional sectioning and evaluation of the cases can reduce the number of pT0 RPs after a positive biopsy. In particular, the current study showed that the final incidence was 0.15% and included only two RPs with missing parts, probably due to incomplete removal of the prostate. One of these two patients was hormonally treated preoperatively.
Our findings on the role of immunohistochemistry to detect residual PCa cells are in agreement with previous studies. Gleave et al. [
8] found that 50% of the cases that exhibited no residual cancer on routine pathologic assessment had remaining foci of cancer discovered by immunostaining. Without the aid of additional step sections and immunostaining for cytokeratin, these cases would have been reported as being stage pT0 [
2].
DNA identity on formalin-fixed tissue from the paraffin blocks is a useful test to establish specimen identity and to exclude the possibility of laboratory error when no residual cancer is found on RP after a positive biopsy. In particular, DNA analysis is a useful test that eliminates the possibility of specimen mishandling or switching by establishing the identity of the tissue from the positive biopsy and the RP. It can be performed in the formalin-fixed tissue from the paraffin blocks. Different methods are used to investigate tissue specimen identity. These include immunolabeling of blood group antigens [
22], sex chromosome targeting using fluorescence in situ hybridization [
21] and microsatellite analysis. According to some authors, microsatellite analysis is the gold standard for investigating tissue identity [
1,
10,
23,
28,
31].
In our study, the clinical and the biopsy data in patients with no initial residual cancer on radical prostatectomy after positive biopsy are similar to the findings from a recent study in patients with single-core positive biopsies and minimal cancer on biopsy [
28,
29]. The majority of patients with no residual cancer on prostatectomy demonstrated minute cancer foci in one or two biopsy cores with Gleason score of 6, which, in many cases, may reflect minimal disease [
28]. Rare small-volume cancers of higher grade may also be encountered [
28]. Follow-up investigations have, in general, shown that no pT0 patient has clinical or biologic evidence of prostate cancer recurrence or progression [
6,
14,
20,
27].
There are four aspects that we have not explored in our study. One is that the carcinoma could be lost in facing off of the paraffin blocks. We are fully aware of this potential problem. Our technicians are instructed so that they have to collect tissue sections and not waste material when the paraffin blocks are levelled off. The second is whether the time, effort and expense of the sampling described in this paper are warranted on a routine basis for all pT0 cases. We have not done any analysis in these respects due to the fact that the number of cases is very small and that time and expense do not represent an issue of concern in our institution. The third is what degree of sampling would be necessary to serially section through the entire prostate. Probably thousands of sections would be required, and we were prepared to cut as many sections as needed to find cancer. The fourth is whether there is an outcome difference when the initial pT0 carcinomas are detected after more thorough sampling vs pT0 cases without additional sampling. This was not addressed in our study because the basic aim was to avoid that a pT0 report is rendered to the clinician and to the patient, thus triggering a potential legal issue with all the problems related to it.
There are few observations in the literature on pT0 cases and preoperative diagnosis of cancer made in TURP specimens. The real incidence of no residual cancer after cancer detected by TURP material is not known and is reported to be seen in 6 to 39% of cases [
9], presumably due to tumour ablation during the initial resection. However, studies of this phenomenon are limited by variations in the number of tissue sections submitted for histological evaluation and by the small number of cases [
3].