Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance

doi:10.1016/j.urology.2017.06.014

Urology

Volume 107, September 2017, Pages 184-189

https://doi.org/10.1016/j.urology.2017.06.014 Get rights and content

Objective

To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS).

Materials and Methods

Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling.

Results

Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years.

Conclusion

Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.

Section snippets

Patient Population

Patients were identified from an institutional AS database, currently composed of 635 men managed with AS at a large, tertiary care academic center between 2002 and 2015. Institutional board approval was obtained before all data collection.

Data collection and cohort characteristics have previously been described in detail.¹⁰ The practice of AS at our institution typically consists of the following: periodic clinic visits every 6-12 months with prostate-specific antigen (PSA) measurements and

Results

In total, 635 patients were identified who were enrolled in AS at our institution. We excluded patients who did not receive a confirmatory biopsy within 1 year (n = 175), reclassified on the confirmatory biopsy (n = 89), did not receive a third biopsy (n = 136), or had an initial Gleason outside of grade groups 1 and 2 (n = 11). This resulted in a final cohort of 224 patients. Roughly half of this final cohort (n = 111, 49.6%) had a negative confirmatory biopsy. The remainder (n = 113, 50.4%)

Comment

In this study, we report the outcomes of grade and volume reclassification in men on AS, grouped by the result of their confirmatory biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a 49% decrease in the hazard of grade reclassification (HR, 0.51) and a 68% decrease in the hazard of volume reclassification (HR, 0.32). Our results are comparable with those of prior studies, which also found a decrease in risk of reclassification in patients with a negative

Conclusion

Detectable pathology on confirmatory biopsy is an important predictor of subsequent reclassification on AS. Absence of cancer on the confirmatory biopsy is associated with a 49% decrease in the risk of grade reclassification and a 68% decrease in the risk of volume reclassification for men on AS. A less intense surveillance regimen may be considered in patients with a negative confirmatory biopsy.

References (24)

M.A. Dall'Era et al.
Active surveillance for prostate cancer: a systematic review of the literature
Eur Urol
(2012)
L.-M. Wong et al.
A negative confirmatory biopsy among men on active surveillance for prostate cancer does not protect them from histologic grade progression
Eur Urol
(2014)
K.C. Cary et al.
Predictors of pathologic progression on biopsy among men on active surveillance for localized prostate cancer: the value of the pattern of surveillance biopsies
Eur Urol
(2014)
A. Adamy et al.
Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer
J Urol
(2011)
M.C. Benson et al.
The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen
J Urol
(1992)
I.F. San Francisco et al.
Risk stratification and validation of prostate specific antigen density as independent predictor of progression in men with low risk prostate cancer during active surveillance
J Urol
(2011)
K.S. Tseng et al.
Risk stratification of men choosing surveillance for low risk prostate cancer
J Urol
(2010)
M. Bul et al.
Active surveillance for low-risk prostate cancer worldwide: the PRIAS study
Eur Urol
(2013)
R.Y. Coley et al.
Prediction of the pathologic Gleason score to inform a personalized management program for prostate cancer
Eur Urol
(2017)
D.P. Ankerst et al.
Precision medicine in active surveillance for prostate cancer: development of the canary-early detection research network active surveillance biopsy risk calculator
Eur Urol
(2015)

A. ElShafei et al.

More favorable pathological outcomes in men with low risk prostate cancer diagnosed on repeat versus initial transrectal ultrasound guided prostate biopsy

J Urol

(2016)

J.J. Tosoian et al.

Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program

J Urol

(2010)

Cited by (11)

Impact of a negative confirmatory biopsy on risk of disease progression among men on active surveillance for prostate cancer
2023, Urologic Oncology: Seminars and Original Investigations
Most prostate cancer active surveillance (AS) protocols suggest a confirmatory biopsy within 12 to 18 months of diagnosis to mitigate the risk of unsampled high-grade disease. We investigate whether the results of confirmatory biopsy impact AS outcomes and could be used to tailor surveillance intensity.
We retrospectively reviewed our institutional database of prostate cancer patients managed by AS from 1997 to 2019 who underwent confirmatory biopsy and ≥3 biopsies overall. Biopsy progression was defined as either an increase in grade group or an increase in the proportion of positive biopsy cores to >34% and was compared between patients with a negative vs positive confirmatory biopsy using the Kaplan-Meier method and Cox proportional hazards regression.
We identified 452 patients meeting inclusion criteria for this analysis, of whom 169 (37%) had a negative confirmatory biopsy. With a median follow-up of 6.8 years, 37% of patients progressed to treatment, most commonly due to biopsy progression. A negative confirmatory biopsy was significantly associated with biopsy progression-free survival in multivariable analysis (HR 0.54, 95% CI 0.34–0.88, P = 0.013), adjusting for known clinical and pathologic factors, including use of mpMRI prior to confirmatory biopsy. Negative confirmatory biopsy was also associated with an increased risk of adverse pathologic features at prostatectomy but not with biochemical recurrence among men who ultimately underwent definitive treatment.
A negative confirmatory biopsy is associated with a lower risk of biopsy progression. While the increased risk of adverse pathology at time of definitive treatment sounds a small cautionary note regarding decreasing surveillance intensity, the majority of such patients have a favorable outcome on AS.
Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a “Negative Core” in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis
2020, Urology
Citation Excerpt :
In our study, we found that the SEL iteration, which excludes GG1 CaP, predicted more favorable nomogram outcomes when compared to the ORIG iteration, including reduced risk of LNI, ECE, SVI, and higher rates of OCD. Conceptually, this would seem intuitive, as removing GG1 CaP cores decreases total percentage of positive cores, thereby decreasing predicted cancer burden.24 More importantly, we validated nomogram outcomes using final RP pathology.
To assess the impact of excluding Gleason Grade Group 1 (GG1) prostate cancer (CaP) cores from current pre-radical prostatectomy (RP) nomograms.
Multi-institutional retrospective chart review was performed on all RP patients with prostate biopsy between 2008 and 2018. Patients were individually assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti nomograms using the following iterations: (1) Original [ORIG] – all available core data and (2) Selective [SEL] – GG1 cores considered negative. Nomogram outcomes – lymph node invasion (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations and stratified based on biopsy GG. Clinically significant impact on management (CSIM) was defined as change in LNI risk above or below 2% or 5% (Δ2/Δ5). Nomogram outcomes were validated with RP pathology.
7718 men met inclusion criteria. In men with GG2 who also had GG1 cores, SEL better predicted LNI (MSKCC – ORIG 4.97% vs SEL 3.50%; Briganti – ORIG 4.81% vs SEL 2.49%, RP outcome 2.46%), OCD (MSKCC – ORIG 40.91% vs SEL 48.44%, RP outcome: 68.46%) and ECE (MSKCC – ORIG 57.87% vs SEL 50.38%, RP outcome: 30.41%), but not SVI (MSKCC – ORIG 5.42% vs SEL 3.34%, RP outcome: 5.62%). This was also consistent in patients with GG3-5 disease. The greatest CSIM was on GG1-2 CaP; Δ2 and Δ5 in GG1 patients was 26.3%-31.0% and 1.5%-5.2%, respectively, and Δ2 and Δ5 in GG2 patients was 3.4%-22.2% and 12.3%-13.6%, respectively.
Excluding GG1 CaP cores from pre-RP nomograms better predicts final RP pathologic outcomes. More importantly, this may better reflect extent of true cancer burden.
Value of Tracking Biopsy in Men Undergoing Active Surveillance of Prostate Cancer
2018, Journal of Urology
Citation Excerpt :
Of special note are the other 85 men who, despite tracking biopsy, were found to have no tumor on confirmatory biopsy (fig. 1). As suggested by Ganesan et al, these men may require less vigilance than men with demonstrable tumor at followup.17 Evidence that tracking as described in this study is highly accurate was recently established using sophisticated molecular biology techniques.3
We compared the upgrading rate obtained by resampling precise spots of prostate cancer (tracking biopsy) vs conventional systematic resampling during followup of men on active surveillance.
From 2009 to 2017 in 352 men prostate cancer was Gleason 3 + 3 in 268 and Gleason 3 + 4 in 84 at initial magnetic resonance imaging-ultrasound fusion biopsy. These men subsequently underwent a second fusion biopsy. At the first biopsy session all men underwent 12-core systematic biopsies and, when magnetic resonance imaging visible lesions were present, targeted biopsies. All cancerous sites were recorded electronically. During active surveillance at a second fusion biopsy session 6 to 18 months later tracking and systematic nontracking samples were obtained. The primary outcome measure was an increase in Gleason score (upgrading) at followup sampling, which was stratified by biopsy method.
Overall 91 of the 352 men (25.9%) experienced upgrading at the second biopsy during a median 11-month interval. The upgrade rate in the Gleason 3 + 3 and 3 + 4 groups was 26.9% and 22.6%, respectively. The mean number of cores taken at second biopsy was 12.2 ± 3.3 in men with upgrading and 12.4 ± 4.1 in those who remained stable (p not significant). Men with grade 0 to 4 magnetic resonance imaging targets were all upgraded at approximately the same rate of 20% to 30% (p not significant). However, 58.8% of the men with grade 5 magnetic resonance imaging targets were upgraded. Of the 91 upgrades 48 (53%) were detected only by tracking.
The tracking function of magnetic resonance imaging-ultrasound fusion biopsy warrants further study. When specific sites are resampled in men undergoing active surveillance of prostate cancer, upgrading is detected more often than by nontracking biopsy.
Evaluation of initial prostate cancer biopsies utilizing 3D open-top light-sheet microscopy for detection of early disease
2023, Prostate
Risk of progression following a negative biopsy in prostate cancer active surveillance
2023, Prostate Cancer and Prostatic Diseases
Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis
2021, BJU International

View all citing articles on Scopus

: Financial Disclosure: The authors declare that they have no relevant financial interests.

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OncologyPrognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance

Objective

Materials and Methods

Results

Conclusion

Section snippets

Patient Population

Results

Comment

Conclusion

Eur Urol

Eur Urol

Eur Urol

J Urol

J Urol

J Urol

J Urol

Eur Urol

Eur Urol

Eur Urol

J Urol

J Urol

Oncology
Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance