Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria

What's known on the subject? and What does the study add? Prostate cancer characterisation, based on laboratory findings, clinical examination and histopathological cancer features that are used to define selection criteria for AS, is not ideal. Consequently, a panel of strict or more lenient criteria to select patients for AS have been published. Studies investigating the relationship between pretreatment variables and final pathology have been done in the past showing the risk of cancer misclassification for some criteria. No study has presented an overview of cancer selection using a panel of 16 currently used AS criteria that is presented in the present study. In an exactly defined cohort after radical prostatectomy, each set of criteria was used as a diagnostic test to separate between patients with more favourable (pT2, no Gleason upgrade between biopsy grading and final pathology) and unfavourable cancer features (pT3, pN+, Gleason upgrade). To the best of our knowledge a comparison of test quality criteria for AS criteria given by sensitivity, specificity, positive and negative predictive value and likelihood ratio has not yet been reported. Moreover, we showed that tumour characterisation, by a formally sufficient 12-core biopsy, in the present dataset harboured a risk of ≈20% that unfavourable cancer features were missed regardless of whether strict or more lenient selection criteria for AS were chosen.

Objective: To evaluate final histopathological features among men diagnosed with prostate cancer eligible for low-risk (LR) or active surveillance (AS) criteria.

Patients and methods: Retrospective application of 16 definitions for AS or LR prostate cancer to a contemporary (January 2008 to March 2011) open retropubic radical prostatectomy (RRP) series of 1745 patients.

Exclusion criteria: neoadjuvant hormones, radiotherapy, inadequate histopathological reports, <10 biopsy cores. Report on the number of men with insignificant tumours (defined as: ≤pT2, Gleason score ≤6, tumour volume <0.5 mL) and men who had unfavourable tumour characteristics on final pathology (defined as: extracapsular extension or seminal vesicle invasion or lymph node metastasis or Gleason upgrading). Sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) were calculated.

Results: Eligibility of patients in the final study cohort (n = 1070) varied from 5.1% to 92.7% depending on the AS or LR criteria used. Final pathology revealed 77 insignificant cancers and 578 patients who had unfavourable histopathological criteria. The detection rate for insignificant cancers on final pathology was variable ranging from 7.8% to 28.3% depending on the AS- or LR-prediction tool used; unfavourable tumour characteristics were found in up to 33.5% on final pathology. The sensitivity, specificity, PPV and NPV were 8.5-97.9%, 24.7-97.8%, 67.7-89.1% and 45.3-78.2%, respectively. The likelihood ratio to correctly identify a patient with LR disease on final pathology ranged from 1.3 to 8.

Conclusions: AS or LR criteria have a significant risk of cancer misclassification. Better prediction tools are needed to improve these criteria. Re-biopsy might improve safety and should be considered more frequently in patients who opt for AS.