scholarly journals A novel predictor of clinical progression in patients on active surveillance for prostate cancer

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.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 222-222
Author(s):  
Andrew Gusev ◽  
Florian Rumpf ◽  
Keyan Salari ◽  
Jeffrey Twum-Ampofo ◽  
Matthew F Wszolek ◽  
...  

222 Background: Active surveillance (AS) is an accepted management strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However, how patients’ risk of disease progression evolves over time during AS has not been well defined. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. Methods: We reviewed our institutional database of 1254 men enrolled in AS for localized PCa from 1996-2016. Our AS protocol includes prostate specific antigen (PSA) and digital rectal exam (DRE) every 4-6 months for 3 years, then annually. Mandatory confirmatory 12 core biopsy is done at 12-18 months. Multiparametric magnetic resonance imagining (mpMRI) or additional systematic or MRI-fusion biopsies are done at the discretion of physician and patient. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. Results: Of 1254 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. Conclusions: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 196-196
Author(s):  
Juan Javier-Desloges ◽  
Tyler Nelson ◽  
Patrick Travis Courtney ◽  
Rishi Deka ◽  
Vinit Nalawade ◽  
...  

196 Background: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. Methods: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. Results: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p<0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). Conclusions: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols.


2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Srinath Kotamarti* ◽  
Andrew Wood ◽  
Alyssa Yee ◽  
Daniel Rabinowitz ◽  
Allison Marziliano ◽  
...  

2021 ◽  
Author(s):  
Xianzhi Zhao ◽  
Yusheng Ye ◽  
Haiyan Yu ◽  
Lingong Jiang ◽  
Chao Cheng ◽  
...  

Abstract Objective To evaluate the efficacy and toxicity of SBRT for localized prostate cancer (PCa). Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray) from October 2012 to July 2019. Follow-up was performed every 3 months for evaluations of efficacy and toxicity. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of the NCCN risk classification) with a median age of 76 years (range: 54–87 years) received SBRT. The median dose was 36.25Gy (range: 34-37.5Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6% respectively. Urinary symptoms were all alleviated after SBRT. All the patients tolerated SBRT with only 1 (0.8%) and 1 (0.8%) patient reporting grade-3 acute and late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.


Author(s):  
Francesco Giganti ◽  
Armando Stabile ◽  
Vasilis Stavrinides ◽  
Elizabeth Osinibi ◽  
Adam Retter ◽  
...  

Abstract Objectives The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol. Methods A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves. Results Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53–98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1–3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4–5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density. Conclusions Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. Key Points • Patients without radiological progression on MRI (PRECISE 1–3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4–5) during AS. • Patients with radiological progression on MRI (PRECISE 4–5) during AS showed a trend to an increase in PSA density.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 1-1 ◽  
Author(s):  
Suneil Jain ◽  
Danny Vesprini ◽  
Alexandre Mamedov ◽  
D. Andrew Loblaw ◽  
Laurence Klotz

1 Background: Active surveillance (AS) is an accepted management strategy for localized prostate cancer. However, the rate of pathological upgrading has not been well described in mature study cohorts. Furthermore, concern exists over the possibility of prostate cancer dedifferentiation with time in patients on AS. Methods: Patients in our prospectively collected AS database with at least one repeat prostate biopsy were included. Linear regression analysis was used to estimate the proportion of patients upgraded (Gleason 6 to 3+4 or higher, Gleason 3+4 to 4+3 or higher) with time from diagnostic biopsy. Results: 593 of 862 patients in our cohort had at least one repeat biopsy. Median follow-up was 6.4 years (max. 20.2 years). The total number of biopsies ranged from 2 to 6. 20% of patients were intermediate risk, 0.3 % high risk, all others low risk. 31.2% of patients were upgraded during active surveillance. The proportion of patients upgraded increased with time, suggesting prostate cancer dedifferentiation occurred at a rate of 1.0%/year (95%CI -0.12 to 2.16%/year). The estimated rate of increase was 2.5 times higher in patients with intermediate risk disease at diagnosis (rate 1.9%/year, 95%CI -0.7-4.6) compared with those with low risk disease (rate 0.75%/year, 95%CI -0.5-2.0). Further analysis is underway. 62% of upgraded patients (n=114) went on to have active treatment. Patients who were upgraded and treated had significantly greater PSA velocities (median 1.2 ng/ml/y vs 0.42 ng/ml/y, p=0.01) and significantly higher Gleason scores when upgraded, than those who remained on surveillance (21.8% vs 2.8% Gleason 8-10, p<0.01). Conclusions: This is the largest re-biopsy cohort, with long-term follow-up, described to date, enabling the first estimates of prostate cancer dedifferentiation in patients on AS. Dedifferentiation rates appear higher in patients with intermediate risk prostate cancer compared with those who are low risk at baseline.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 43-43
Author(s):  
Thomas P. Frye ◽  
Nabeel Ahmad Shakir ◽  
Steven Abboud ◽  
Arvin Koruthu George ◽  
Maria J Merino ◽  
...  

43 Background: Active surveillance (AS) is an established treatment option for men with low risk prostate cancer. Its role in intermediate prostate cancer is still being investigated. Recent studies have shown that multiparametric-MRI (mp-MRI) along with MRI-TRUS fusion-guided biopsy may better assess risk in patients eligible for AS, compared to 12-core biopsy, due to improved detection of clinically significant cancers. The objective is to determine the performance of MRI-TRUS guided biopsy for men on AS with both low and intermediate risk disease. Methods: Between 2007-2014 men on AS were included if they had complete mp-MRI and pathology data for 2 or more MRI-TRUS biopsy sessions. Fusion guided biopsy procedures consisted of MRI identified targeted biopsies as well as random 12 core biopsies. Men were allowed to participate in AS with low and intermediate risk prostate cancer, Gleason score ≤ 3+4=7. Progression was defined by patients with initial Gleason 3+3=6 to any Gleason 4, and Gleason 3+4=7 disease progressing to a primary Gleason 4 or higher. Results: 89 men met our study criteria with an average age of 62 years old (range 45-79). 75 men had low risk Gleason 3+3=6 at the outset of AS by 1st biopsy session with a median PSA 5.1 ng/ml. The other 14 men had intermediate risk prostate cancer Gleason 3+4=7 at the outset of AS and a median PSA 4.6 ng/ml. During follow-up, 25 (33%) low risk men progressed to 3+4 or above at a median of 20.6 months. Of these, 19 were found by targeted biopsy. 6 (43%) of the intermediate risk men progressed to Gleason 4+3=7 at a median of 36.8 months. 4 of these progressed on targeted fusion biopsy. In the intermediate risk men, 84 random biopsy cores were require to detect 1 progression versus 15 targeted biopsy cores to detect 1 progression. Conclusions: The majority of patients on AS who progressed were identified by MRI-TRUS targeted biopsy. Less biopsy cores are required to detect progression with targeted biopsy. These results are preliminary and a larger cohort with longer follow-up would be beneficial.


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