Active Surveillance Program for Prostate Cancer: An Update of the Johns Hopkins Experience

2011 ◽  
Vol 29 (16) ◽  
pp. 2185-2190 ◽  
Author(s):  
Jeffrey J. Tosoian ◽  
Bruce J. Trock ◽  
Patricia Landis ◽  
Zhaoyong Feng ◽  
Jonathan I. Epstein ◽  
...  

Purpose We assessed outcomes of men with prostate cancer enrolled in active surveillance. Patients and Methods Since 1995, a total of 769 men diagnosed with prostate cancer have been followed prospectively (median follow-up, 2.7 years; range, 0.01 to 15.0 years) on active surveillance. Enrollment criteria were for very-low-risk cancers, defined by clinical stage (T1c), prostate-specific antigen density < 0.15 ng/mL, and prostate biopsy findings (Gleason score ≤ 6, two or fewer cores with cancer, and ≤ 50% cancer involvement of any core). Curative intervention was recommended on disease reclassification on the basis of biopsy criteria. The primary outcome was survival free of intervention, and secondary outcomes were rates of disease reclassification and exit from the program. Outcomes were compared between men who did and did not meet very-low-risk criteria. Results The median survival free of intervention was 6.5 years (range, 0.0 to 15.0 years) after diagnosis, and the proportions of men remaining free of intervention after 2, 5, and 10 years of follow-up were 81%, 59%, and 41%, respectively. Overall, 255 men (33.2%) underwent intervention at a median of 2.2 years (range, 0.6 to 10.2 years) after diagnosis; 188 men (73.7%) underwent intervention on the basis of disease reclassification on biopsy. The proportions of men who underwent curative intervention (P = .026) or had biopsy reclassification (P < .001) were significantly lower in men who met enrollment criteria than in those who did not. There were no prostate cancer deaths. Conclusion For carefully selected men, active surveillance with curative intent appears to be a safe alternative to immediate intervention. Limiting surveillance to very-low-risk patients may reduce the frequency of adverse outcomes.

2011 ◽  
Vol 29 (20) ◽  
pp. 2795-2800 ◽  
Author(s):  
Sima P. Porten ◽  
Jared M. Whitson ◽  
Janet E. Cowan ◽  
Matthew R. Cooperberg ◽  
Katsuto Shinohara ◽  
...  

Purpose Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time. Patients and Methods Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates. Results Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy. Conclusion A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.


Author(s):  
Matthew Cooperberg ◽  
Peter Carroll

Management of prostate cancer remains controversial, in large part because of its wide heterogeneity in terms of aggressiveness and prognosis. Early detection efforts based on prostate specific antigen (PSA) and aggressive treatment of high-risk cancers have yielded major improvements in mortality rates, but overtreatment of low-risk cancers—those unlikely to cause symptoms or threaten life if they were never detected—is associated with high rates of avoidable toxicity and cost. Prostate cancer can be effectively risk-stratified based on tools (e.g. nomograms, CAPRA score) integrating the PSA level, Gleason grade, clinical stage, and extent of biopsy tissue involvement. Most men with low-risk tumours are eligible for active surveillance, a programme of careful monitoring based on PSA and follow-up biopsies. Men with higher-risk cancers are best served with radical prostatectomy or radiation therapy.


2010 ◽  
Vol 28 (17) ◽  
pp. 2810-2816 ◽  
Author(s):  
Ashley E. Ross ◽  
Stacy Loeb ◽  
Patricia Landis ◽  
Alan W. Partin ◽  
Jonathan I. Epstein ◽  
...  

Purpose To assess the predictive ability of prostate-specific antigen (PSA) velocity (PSAV) and doubling time (PSADT) for biopsy progression and adverse pathology at prostatectomy among men with low-risk prostate cancer enrolled on an active-surveillance program. Methods We evaluated 290 men who met criteria for active surveillance (ie, PSA density < 0.15 ng/mL/cm3 and Gleason score ≤ 6 with no pattern ≥ 4, involving ≤ 2 cores with cancer, and ≤ 50% involvement of any core by cancer) with two or more serial PSA measurements after diagnosis from 1994 to 2008. Follow-up included twice-yearly digital rectal exam and PSA measurements and yearly surveillance biopsy. Treatment was recommended for biopsy progression (ie, Gleason score ≥ 7, or > 2 positive cores, or > 50% core involvement). Sensitivity and specificity of postdiagnostic PSAV and PSADT were explored by using receiver operating characteristic (ROC) analysis. Results Overall, 188 (65%) men remained on active surveillance, and 102 (35%) developed biopsy progression at a median follow-up of 2.9 years. PSADT was not significantly associated with subsequent adverse biopsy findings (P = .83), and PSAV was marginally significant (P = .06). No PSAV or PSADT cut point had both high sensitivity and specificity (area under the curve, 0.61 and 0.59, respectively) for biopsy progression. In those who eventually underwent radical prostatectomy, PSAV (P = .79) and PSADT (P = .87) were not associated with the presence of unfavorable surgical pathology. Conclusion Postdiagnostic PSA kinetics do not reliably predict adverse pathology and should not be used to replace annual surveillance biopsy for monitoring men on active surveillance.


2018 ◽  
Vol 12 (1) ◽  
pp. 54-59
Author(s):  
Ekrem Islamoglu ◽  
Erdem Kisa ◽  
Cem Yucel ◽  
Orcun Celik ◽  
Ozgur Cakmak ◽  
...  

Purpose: We assessed the outcomes of men with low-risk prostate cancer enrolled in active surveillance. Methods: From January 2008, patients in our clinic who were classified as having low-risk prostate cancer according to the D’Amico classification were included in the protocol. Follow-up consisted of regular prostate-specific antigen tests, digital rectal examinations and biopsies. Outcomes were compared between men who progressed and those who did not, and survival analysis was obtained. Results: The mean follow-up period was 46 months. A total of six patients received curative treatment during follow-up as a result of meeting progression criteria. The mean follow-up time from the beginning of active surveillance until curative therapy was 27.1 months. Four of our 64 patients lost their lives due to diseases other than prostate cancer, none of the patients were lost due to prostate cancer. When patients who showed progression and those who did not were compared in terms of positive core numbers and the core tumour percentage we found no significant difference between the two groups ( P>0.05) Conclusion: Active surveillance seems to be a safe and feasible practice in men with low-risk prostate cancer. Gleason score, clinical stage and initial prostate-specific antigen seem to be the most definite criteria for the selection of patients, while it is thought that the number of positive cores is a matter that can be dealt with more flexibility. Level of evidence: Not applicable for this multicentre audit.


Author(s):  
Niranjan Sathianathen

This chapter provides a summary of an important observational study of men with clinically localized, mostly favorable-risk prostate cancer who were followed with active surveillance, which consisted of periodic prostate-specific antigen testing and repeat biopsies. It found that local treatment with curative intent can be safely deferred long term in many patients as long as they are carefully monitored.


2021 ◽  
Vol 93 (4) ◽  
pp. 385-388
Author(s):  
Mohammad Hout ◽  
Ali Merhe ◽  
Nassib Abou Heidar ◽  
Jose M. El-Asmar ◽  
Wassim Wazzan ◽  
...  

Background: The aim of our study was to evaluate the outcome of active surveillance (AS) for prostate cancer for a cohort of patients at our institution. Methods: A total of 43 patients with low risk prostate cancer were enrolled in an active surveillance pilot program at our institution between 2008 and 2018. Follow up protocols included: periodic prostate specific antigen (PSA), digital rectal examination (DRE), multiparametric MRI, and prostate biopsy at one year. Pertinent parameters were collected, and descriptive statistics were reported along with a subset analysis of patients that dropped out of the protocol to receive active treatment for disease progression. Results: Out of 43 eligible patients, 46.5% had a significant rise in follow up PSA. DRE was initially suspicious in 27.9% of patients, and none had any change in DRE on follow up. Initially, prostate MRIs showed PIRADS 3, 4, and 5 in 14%, 37.2%, and 11.6% respectively, while 23.2% had a negative initial MRI. 14% did not have an MRI. Upon follow up, 18.6% of patients had progression on MRI. Initial biopsies revealed that 86% were classified as WHO group 1, while 14% as WHO group 2. With regards to the follow up biopsies, 11.6% were upgraded. 20.9% of our patients had active treatment; 44.4% due to upgraded biopsy results, 22.2% due to PSA progression, 22.2% due to strong patient preference, and 11.1% due to radiologic progression. Conclusions: For selected men with low risk prostate cancer, AS is a reasonable alternative. The decision for active treatment should be tailored upon changes in PSA, DRE, MRI, and biopsy results.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 217-217 ◽  
Author(s):  
Aini Azmi ◽  
Ruth Dillon ◽  
Laure Marignol ◽  
Simona Borghesi ◽  
Mary Dunne ◽  
...  

217 Background: Active surveillance (AS) is a recognized treatment option for patients with low-risk prostate cancer (PCa). We carried out a web-based survey to evaluate how AS is practiced by European urologists and to review criteria for patient selection, follow up and indications for intervention. Methods: 2959 potential participants were identified via various European urological association databases and invited via email to complete an online survey consisting of 19 questions. Only urologists practising in an EU country were eligible to participate. Results: 226 urologists participated in the survey corresponding to a response rate of 8%. None of the 19 questions were answered by all urologists, therefore results exclude the missing data. 220 (97%) urologists offer AS. 48% (n=103/216) and 24% (n=53/216) urologists offer AS within the context of an official protocol or clinical trial respectively. The most used factors in selecting patients are Gleeson score (GS) ≤3+3=6 (n=174/202, 86%) and PSA ≤10ng/ml (n=171/200, 85%). 48% (n=96/201) only include patients with ≤2 cores positive while 18% (n=37/201) include those with <50% positive biopsy cores. 41% urologists (n=82/202) only include patients with a clinical stage ≤T1cN0M0. MRI pelvis is performed as a baseline investigation by only 28% (n=57/200). All responding urologists (n=194) use serial PSA to follow up their patients. 89% (n=172/194) carry out serial DRE while 83% (n=161/194) perform repeated prostate biopsy. Re-biopsy is performed within the first year of AS by 77% of urologists (n=131/171). Only 8% (n=15/193) use serial MRI pelvis to monitor their patients. The follow up intensity also varies widely. GS progression was the most frequently cited trigger for intervention (n=168/192, 87%) followed by PSA doubling time of ≤3 years (n=115/192, 60%). Conclusions: Several internationally published guidelines on PCa treatment have recommended AS as a therapeutic option for patients with low-risk PCa. However presently there is a lack of consensus on an optimal AS protocol. This survey shows the wide variation in the practice of AS across Europe and highlights the need for patients to be included in clinical trials to enable an evidence-based guideline to be established.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 38-38
Author(s):  
Itay Aharon Sternberg ◽  
Changhong Yu ◽  
Gal Elimelech Keren Paz ◽  
Philip H. Kim ◽  
Melanie Bernstein ◽  
...  

38 Background: Due to the inability to predict progression and need for treatment, patients with low-risk prostate cancer (LRPC) managed by active surveillance (AS) are subjected to repeated biopsies and their possible complications. We developed a nomogram predicting the risk of progression in patients on AS for LRPC. Methods: A retrospective review of all patients enrolled in an AS program at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1993 and 2012 was conducted. Demographic, clinical, and pathologic data for patients who met the inclusion criteria for AS (cT1 or cT2a, prostate-specific antigen [PSA] less than 10, Gleason 6 or less, no more than three positive biopsy cores and no greater than 50% involvement of any single core) on the diagnostic and the confirmatory biopsies were collected and used to develop a nomogram for predicting progression-free probability. Multivariable logistic regression analysis was used to model the association between each risk variable (age, PSA levels, clinical stage, biopsy features) and disease progression. Progression was defined as failure to meet the inclusion criteria during follow up. Results: A total of 1,095 patients were enrolled in an AS program at MSKCC during the study period, of which 680 met the inclusion criteria for AS on both the diagnostic and the confirmatory biopsies and had available follow-up. At a median follow-up of 3 years 101 patients progressed. A nomogram predicting the progression-free probability was designed based on characteristics at diagnosis, result of a confirmatory biopsy and the number of negative and positive surveillance biopsies to date. A concordance index of 0.596 was calculated. Conclusions: Conditioned upon external validation, this nomogram can be used to counsel patients on their risk of progression and their surveillance protocol can be adjusted appropriately, possibly avoiding unnecessary biopsies and preventing biopsy-related complications.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 40-40
Author(s):  
Christopher James Welty ◽  
Pauline Fillipou ◽  
Janet E. Cowan ◽  
Peter Carroll

40 Background: Little is known about the risk of delaying radical prostatectomy (RP) until biopsy progression following active surveillance (AS) for prostate cancer. This study examines the pathological outcomes associated with surgery following AS compared to immediate treatment of prostate cancer with similar grades. Methods: Men who underwent RP between 1997-2013 at University of California San Francisco were included. The first comparison consisted of men who met strict AS inclusion criteria (Gleason Score ≤ 6, PSA ≤ 10, clinical stage <T3, ≤ 33% biopsy cores positive, and <= 50% of any single core positive) at diagnosis and underwent AS prior to RP (AS+RP) compared to men who met strict AS criteria and underwent RP within 6 monts (immediate RP). The second comparison consisted of men who met strict AS criteria and were upgraded on follow-up biopsy compared to a cohort of men matched on the basis pre-treatment biopsy pathology. Logistic regression was used to determine associations of RP group with adverse pathology (stage ≥pT3/N1, positive margins, and/or upgrade to Gleason >=4+3), adjusting for clinical and demographic factors. Results: We identified 241 men who underwent RP after a period of AS, 157 of whom initially met strict AS criteria. The median time to RP was 20 months (IQR 14-36). Men who met strict criteria and underwent immediate RP were less likely to have unfavorable pathology than those who underwent AS+RP (OR 0.39, 95% CI 0.24-0.62). Fifty-four of the men who underwent AS+RP did so have upgrading to Gleason 3+4 disease. These patients were matched with 154 men based on their pre-treatment biopsy features. After appropriate matching, the timing of RP was not associated with adverse pathology (OR 1.27, 9% CI 0.65-2.49). Conclusions: Men who undergo surgery following AS are a selected subset of men with low risk prostate cancer. The surgical pathology features of these patients are more similar to men undergo surgery after diagnosis with intermediate risk prostate cancer than those diagnosed with very low risk disease. Additional follow-up of this and other cohorts is needed to assess long term clinical outcomes following delayed RP.


2019 ◽  
Vol 13 (8) ◽  
Author(s):  
Guan Hee Tan ◽  
Antonio Finelli ◽  
Ardalan Ahmad ◽  
Marian Wettstein ◽  
Alexandre Zlotta ◽  
...  

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP).     Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years follow-up. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo / prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival curves between TCLo density groups. Test characteristics of TCLo were explored with receiver operating characteristic (ROC) curves.     Results: We included 181 patients who had CBx between 2012-2015, and met inclusion criteria. The mean age of patients was 62.58 years (SD=7.13) and median follow-up was 60.9 months (IQR=23.4). A high TCLo density score (>0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p<0.001), and GP (HR 3.85, 95% CI: 1.91-7.73, p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression.     Conclusion: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PC.


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