Active Surveillance Eligibility Criteria Research Articles

High prevalence of HPV16 and high-grade cytology in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.

Many countries have adopted active surveillance in women with cervical intraepithelial neoplasia grade 2 (CIN2), leaving the lesion untreated. However, there is a lack of consensus on the eligibility criteria for active surveillance across countries, with some abstaining from active surveillance in women with human papilloma virus 16 (HPV16) or a high-grade cytology. Here, we aimed to describe the distribution of HPV genotypes, age, and cytology in women undergoing active surveillance for CIN2. We conducted a single-center cross-sectional study on women aged 23-40 undergoing active surveillance for CIN2 during 2000-2010. Women were identified through the Danish Pathology Data Bank (DPDB) at Aarhus University Hospital, Denmark. We collected information on basic characteristics and results of histopathological examinations via DPDB. Women were deemed eligible for inclusion if they had a subsequent biopsy after index CIN2, and had no prior record of CIN2+, hysterectomy, or cone biopsy. Archived biopsies underwent HPV genotyping using the HPV SPF10 - DEIA-LiPA25 system, and the diagnosis was re-evaluated by three expert pathologists. We used the Chi squared-test (p-value) for comparison across groups. We identified 3623 women with CIN2 of whom 455 (12.6%) were included. Most women were 30 years or younger (73.8%), and half (48.8%) had a high-grade index cytology. The prevalence of any high-risk HPV was 87.0%, with HPV16 being the most prevalent genotype (35.6%). The prevalence of HPV16 was significantly higher in women aged 30 or younger (39.3%) compared to women older than 30 years (25.2%) (p = 0.006). Upon expert review, 261 (57.4%) had CIN2 confirmed, whereas 56 (12.3%) were upgraded to CIN3 and 121 (26.6%) were downgraded to CIN1/normal. While the HPV16 prevalence was similar between community and expert confirmed CIN2, the prevalence of HPV16 was significantly higher in women with expert CIN3 compared to women with expert CIN1/normal (64.3% vs. 19.0%, p = 0.001). The high prevalence of HPV16 and high-grade cytology imply that these women may be perceived as a high-risk population and non-eligible for active surveillance in countries outside Denmark. Future studies should investigate the importance of HPV, age, cytology, and expert review on risk of progression to help refine criteria for active surveillance.

Magnetic Resonance Imaging Targeted Biopsy Improves Selection of Patients Considered for Active Surveillance for Clinically Low Risk Prostate Cancer Based on Systematic Biopsies

Current selection criteria for active surveillance based on systematic biopsy underestimate prostate cancer volume and grade. We investigated the role of additional magnetic resonance imaging targeted biopsy in reclassifying patients eligible for active surveillance based on systematic biopsy. We performed a study at 2 institutions in a total of 281 men with increased prostate specific antigen. All men met certain criteria, including 1) prebiopsy magnetic resonance imaging, 12-core transrectal systematic biopsy and 2 additional magnetic resonance imaging targeted biopsies of lesions suspicious for cancer during the same sequence as systematic biopsy, and 2) eligibility for active surveillance based on systematic biopsy results. Criteria for active surveillance were prostate specific antigen less than 10 ng/ml, no Gleason grade 4/5, 5 mm or less involvement of any biopsy core and 2 or fewer positive systematic biopsy cores. Patient characteristics were compared between reclassified and nonreclassified groups based on magnetic resonance imaging targeted biopsy results. On magnetic resonance imaging 58% of the 281 patients had suspicious lesions. Magnetic resonance imaging targeted biopsy was positive for cancer in 81 of 163 patients (50%). Of 281 patients 28 (10%) were reclassified by magnetic resonance imaging targeted biopsy as ineligible for active surveillance based on Gleason score in 8, cancer length in 20 and Gleason score plus cancer length in 9. Suspicious areas on magnetic resonance imaging were in the anterior part of the prostate in 15 of the 28 men (54%). Reclassified patients had a smaller prostate volume (37 vs 52 cc) and were older (66.5 vs 63 years) than those who were not reclassified (p < 0.05). Magnetic resonance imaging targeted biopsy reclassified 10% of patients who were eligible for active surveillance based on systematic biopsy. Its incorporation into the active surveillance eligibility criteria may decrease the risk of reclassification to higher stages during followup.

Defining the threshold for significant versus insignificant prostate cancer

Autopsy studies have shown the presence of a large reservoir of latent prostate cancers in adult men. Serum PSA testing of asymptomatic men leads to the detection of a proportion of these latent prostate cancers. The unequivocal demonstration of a substantial (30-50%) risk of overdiagnosis by the two largest randomized population-based screening trials has led to a growing awareness of this unwanted effect. Unsurprisingly, active surveillance is now becoming the favoured strategy for deferring active treatment in men diagnosed with low-risk prostate cancer and reducing their risk of overtreatment. Almost all eligibility criteria for active surveillance refer to a strict pathological definition of insignificant prostate cancer, based on two landmark studies published about 20 years ago. However, current epidemiological data suggest that this original pathological definition of insignificant prostate cancer is too restrictive. In addition, the International Society of Urological Pathology (ISUP) 2005 modification to the Gleason grading system might have resulted in a marked upgrading of biopsy-diagnosed prostate cancers, reducing the number of men eligible for active surveillance. An updated definition of insignificant prostate cancer should reflect the optimal trade-off between reducing the risk of underestimating a significant prostate cancer and including as many men as possible in active surveillance programmes.

Does Suspicion of Prostate Cancer on Integrated T2 and Diffusion-weighted MRI Predict More Adverse Pathology on Radical Prostatectomy?

To determine whether suspicion for tumor on prostate MRI incorporating T2-weighted imaging (T2-WI) and diffusion-weighted imaging (DWI) predicts more adverse pathology on radical prostatectomy (RP). From 2007 to 2009, 154 patients underwent 1.5 Tesla pelvic-phased-array magnetic resonance imaging (MRI) of the prostate that included T2-WI and DWI before RP. MRI examinations were retrospectively reviewed and grouped by degree of suspicion for tumor: no suspicion for tumor (NST, n= 15), equivocal suspicion for tumor (EST, n= 60), or strong suspicion for tumor (SST, n= 79). The NST/EST groups were combined and compared to the SST group. Preoperative variables were used to assemble a multivariate model. Outcomes reflective of adverse pathology included primary Gleason grade≥4, pathologic stage≥T3 (≥pT3), and tumor upgrading. Subgroup analysis was performed for patients meeting eligibility criteria for active surveillance (n= 55). For this analysis, the NST group was compared to the EST/SST groups. SST status was associated with adverse preoperative risk factors for aggressive disease. Univariate analysis demonstrated significant association between SST and primary Gleason≥4 pathology and stage≥pT3 (P<.05). On multivariate analysis, SST was independently predictive of primary Gleason≥4 pathology (odds ratio [OR] 6.14, 95% confidence interval [CI] 1.97-19.2) and Gleason upgrading (OR 2.47, 95% CI 1.01-6.02). Among patients eligible for active surveillance, those in the NST group had decreased likelihood of Gleason≥7 disease or stage≥pT3 compared to the EST/SST groups (7.7% vs 47.6%, P= .01). Increased tumor suspicion on T2-WI/DWI MRI is indicative of adverse pathology on RP. These findings suggest a role for MRI in pretreatment risk assessment.

Active surveillance in prostate cancer

The long-term safety and effectiveness of active surveillance depends on our ability to select appropriate patients and trigger delayed treatment in those who need it, whereas avoiding intervention in those who do not. In this review, we will consider how recent advances have influenced patient selection for active surveillance and review the range of different intervention triggers that have been proposed. Several large surveillance cohort studies have been reported recently showing excellent medium-term outcomes in well selected patients, with approximately a third of patients going on to have deferred treatment. Debate continues on the most appropriate eligibility criteria for active surveillance and what triggers for intervention should be used. There is growing interest in the role of transperineal template biopsies and multiparametric MRI, both for patient selection and in identifying triggers for intervention. Active surveillance is a well tolerated treatment option in well selected groups of patients. There is no 'one size fits all' set of criteria for patient selection or triggers for intervention but decisions can be guided by information from histology, prostate-specific antigen kinetics and imaging.

Ki67 and BUBR1 May Discriminate Clinically Insignificant Prostate Cancer in the PSA Range &lt;4 ng/ml

We aimed to evaluate the Epstein criteria and the eligibility criteria for active surveillance in the Prostate Cancer Research International study by using immunohistochemical staining. We reviewed the clinicopathological data of 119 patients who underwent prostate biopsy, with prostate-specific antigen levels being ≤4 ng/ml. The data of patients with detected prostate cancer were compared with those of patients with clinically significant prostate cancer. To discriminate insignificant prostate cancer, immunohistochemical staining for Ki67, p53, bcl-2, BUBR1, PTEN and E-cadherin was performed. Ki67, BUBR1 and E-cadherin staining showed significant correlation with the Gleason score. Ki67 and BUBR1 staining showed significant correlations with the Epstein criteria, and Ki67, BUBR1 and E-cadherin staining correlated with the Gleason score and Prostate Cancer Research International criteria. The sensitivity and specificity of Ki67 or BUBR1 staining in discriminating the prostate cancer cases classified as clinically insignificant according to the Epstein criteria were 62.5 and 84.2%, or 57.1 and 100%, respectively. The sensitivity and specificity of Ki67, BUBR1 or E-cadherin staining in discriminating prostate cancer cases classified as clinically insignificant according to the Prostate Cancer Research International criteria were 75 and 87.5%, 66.7 and 100% or 50 and 100%, respectively. The predictive accuracy of Ki67 and BUBR1 staining was equivalently high in relation to both sets of criteria (77.6 and 83.3%, respectively). These data could provide pathological evidence to support the suitability of the Epstein and Prostate Cancer Research International criteria. Ki67 and BUBR1 may be potential markers in selecting candidates for active surveillance.