Nomogram for prostate cancer risk in men with a previous diagnosis of prostatic intraepithelial neoplasia (PIN)

Luigi Benecchi1, Francesco Evaristi1, Michele Potenzoni1, Luca VIviano1, Enrico Gnocchi1, Fernando Enrique Echeverria1, Fabrizio Russo1, Chiara Grassani2, Massimo Melissari3, Dario Somenzi1, Andrea Prati4, Carlo Del Boca1
  • 1 Ospedale Cremona (Cremona)
  • 2 Ospedale Cremona (Parma)
  • 3 Università di Parma (Parma)
  • 4 Ospedale Fidenza (Parma)


:Prostatic intraepithelial neoplasia (PIN) as an isolated diagnostic finding in needle biopsy tissue has previously been associated with subsequent detection of carcinoma in a large number of cases. In most of previous studies, the detection rate was greater than 33%, and in about one half of the series, the proportion of men detected with carcinoma on repeat biopsy was greater than 43%. In contrast, the detection rate after a diagnosis of benign prostatic tissue is around 20%.
The aim of this study is to develop a nomogram that would be useful for counseling patients in the decision to repeat prostate biopsy after a previous diagnosis of prostatic intraepithelial neoplasia (PIN)

Methods and results

Our database of twelve core prostate biopsies performed at our institution from January 2002 to January 2013 was searched for men who repeated prostate biopsy after a previous diagnosis of PIN.
A total of 235 men were included in this study. Median age was 67 years (range 49 to 89). Median PSA was 7.2 ng/ml (range 0.7 to 47). Logistic regression model to predict the presence of prostate cancer at biopsy was fitted using age, prostate cancer family history, digital rectal examination findings (DRE), PSA, percent free PSA, foci of low grade PIN (lgPIN), foci of high grade PIN (hgPIN) and presence of multifocal PIN. The accuracy of the nomogram was quantified with the Harrel′s concordance index and the calibration plot method. Two hundred bootstrap resamples were used for internal validation.
A nomogram for a positive biopsy was developed from the final logistic regression model findings (Figure 1). For internal validation and to decrease overfit bias models were subjected to 200 bootstrap resamples. Calibration in the large was assessed by comparing the average of observed vs predicted prostate cancers. The bootstrapping concordance index of the nomogram was 0.636.


The prostatic intraepithelial neoplasia incidence and its correlation with Prostate cancer have been very variable in the literature, in the range 0.7 – 24% (1, 2, 3, 4, 5) . Many trials have reported a Prostate cancer yield on re-biopsy (as a result of a previous prostatic intraepithelial neoplasia diagnosis) in the range 22 – 100% (5, 6, 7) . Thus, the prostate cancer detection rate after an initial prostatic intraepithelial neoplasia diagnosis has decreased from 40% to 50% in the early 1990s to 10% to 30% in recent studies (2, 8). The change in prostate sampling from sextant to extended or double-sextant protocol is considered to be largely responsible for this decrease (2)
Several investigators have analyzed the prognostic value of PSA, PSAD, patient age, prostate volume, and abnormal DRE and/or TRUS findings in patients with an initial HGPIN diagnosis. However, no consensus has yet been reached regarding when and how to repeat biopsy in patients with an initial HGPIN diagnosis because of the lack of a strong predictive factor suggesting a final positive biopsy. (2)
Our model can reasonably predict prostate cancer in patient with a previous diagnosis of PIN. We recognize that a single pathological outcome may not define the presence of a tumor. Nevertheless, our model provides valuable information to a patient who is considering to repeat or not a prostate biopsy.
In conclusion we successfully developed a model that would be useful for counseling patients in the decision to repeat prostate biopsy after a previous diagnosis of prostatic intraepithelial neoplasia.


1) Naya Y1, Ayala AG, Tamboli P, Babaian RJ. Can the number of cores with high-grade prostate intraepithelial neoplasia predict cancer in men who undergo repeat biopsy? Urology. 2004 Mar;63(3):503-8.
2) Roscigno M, Scattoni V, Freschi M, Abdollah F, Maccagnano C, Galosi A, Lacetera V, Montironi R, Muzzonigro G, Deho F, Deiana G, Belussi D, Chinaglia D, Montorsi F, Da Pozzo LF. Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy. BJU Int. 2012 May;109(9):
3) Gokden N , Roehl K , Catalona WJ et al . High grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: current level of risk in screening population. Urology 2005 ; 6 5 : 538 – 42
4) Girasole CR , Cookson MS , Putzi MJ et al . Signifi cance of atypical and suspicious small acinar proliferation and high grade prostatic intraepithelial neoplasia on prostate biopsy: implication for cancer detection and biopsy strategy . J Urol 2006 ; 175 : 929 – 33
5) Kamoi K , Troncoso P , Babaian RJ . Strategy for repeat biopsy in patients in patients with high grade prostatic intraepithelial neoplasia . J Urol 2000 ; 163 : 819 – 23
6) Park S , Shinohara K , Grossfeld GD , Grossfeld GD , Carroll PR . Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy . J Urol 2001 ; 165 : 1409 – 14
7) Fowler JE , Bigler SA , Miles D , Yalkut DA . Predictors of fi rst repeat biopsy cancer detection with suspected local stage prostate cancer . J Urol 2000 ; 163 : 813 – 18
8) Gallo F , Chiono L , Gastaldi E , Venturino E , Giberti C . Prognostic signifi cante of High-Grade Prostatic Intraepithelial Neoplasia (HGPIN): risk of prostatic cancer on repeat biopsies . Urology 2008 ; 72 : 628 – 32