Management of isolated local failures following stereotactic body radiation therapy for low to intermediate risk prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 66-66
Author(s):  
Nicolette Drescher ◽  
Nima Aghdam ◽  
Malika Danner ◽  
Marilyn Ayoob ◽  
Thomas M. Yung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salvage Therapy ◽  
Doubling Time ◽  
Intermediate Risk ◽  
Effective Treatment Option ◽  
Psa Doubling Time ◽  
Risk Prostate Cancer ◽  
Effective Doses ◽  
Psa Nadir ◽  
Pre Treatment

66 Background: SBRT is a safe and effective treatment option for patients with low to intermediate risk prostate cancer (PCa). SBRT delivers high biologically effective doses resulting in very low PSA nadirs. Strategies to diagnose and confirm salvageable isolated local failures (ILF) are needed. This study aims to examine the incidence and approach to management of ILF after SBRT in a large single institution cohort. Methods: All patients with low or intermediate risk PCa treated with SBRT at our institution were eligible for this study. Treatment was delivered using the robotic SBRT with doses of 35-36.25 Gy in five fractions. ILF were diagnosed using mpMRI and/or biopsy prompted by PSA rise after achieving long-term nadir. Choice of salvage therapy and post-salvage PSA were ascertained on follow up. Results: Between December, 2008 to August, 2018, 998 men with low to intermediate risk prostate cancer were eligible for analysis. Twenty patients (low risk, n = 4; intermediate risk, n = 16) were found to have ILF on either MRI (n = 15) and/or biopsy (n = 17). Three patients with MRI-identified ILF elected active surveillance in lieu of biopsy. Median pre-treatment PSA was 7.5 ng/ml. Median time to diagnosis of ILF was 72 months (37-96 months) with median PSA at the time of ILF of 2.3 ng/ml (1.1-10 ng/ml). Median PSA doubling time was 17 months (5-22 months). Thirteen patients with biopsy proven ILF proceeded with salvage therapy (cryotherapy n = 12, HIFU n = 1). Of 12 patients who underwent cryotherapy, 8 had a post-treatment PSA of < 0.1ng/ml, two patient’s results were unavailable, one patient had a PSA nadir of 0.7 ng/ml and one patient had yet to undergo post-salvage PSA test at the time of this report. Conclusions: The incidence of ILF is rare in our series. Diagnosis and management of ILF post-SBRT continues to evolve in the era of successful salvage therapy. Our report suggests an important role for early utilization of MRI and confirmatory biopsy at relatively low PSA levels and long PSA doubling time. Additionally, undetectable PSA post-salvage therapy supports early treatment after identifying ILF. Larger trials are needed for refinement of patient selection and most appropriate salvage modality.

Prognostic value of copy-number alterations of the Cohesin complex in intermediate-risk prostate cancer recurrence.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 49-49
Author(s):  
Jonathan So ◽  
Melvin Chua ◽  
Emilie Lalonde ◽  
Osman Mahamud ◽  
Alejandro Berlin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Intermediate Risk ◽  
Cohesin Complex ◽  
Biochemical Relapse ◽  
Copy Number Alterations ◽  
Image Guided Radiotherapy ◽  
Image Guided ◽  
Risk Prostate Cancer ◽  
Pre Treatment

49 Background: The Cohesin complex plays a critical role in mitotic progression and post-replicative DNA damage repair. It serves to bring together sister chromatids both in metaphase and in homologous recombination repair following ionizing radiation. The complex has also been shown to be phosphorylated in the ATM/BRCA1 pathway. The expression of various proteins in the complex are dysregulated in many cancers: breast, prostate, etc. Interestingly, in breast cancer cell lines, Cohesin is required for MYC activation in response to estrogen. Our study sought to correlate copy number alterations in this pivotal complex with biochemical relapse in prostate cancer patients. Methods: Our cohort consists of 284 patients with D’ Amico-classified intermediate-risk prostate cancer, treated with image-guided radiotherapy (IGRT, N = 143) or radical prostatectomy (RadP, N = 141). Pre-treatment biopsies and prostatectomy samples were analyzed using the Affymetrix Oncoscan array. The Phoenix and AUA criteria was used to define biochemical relapse for RadP and IGRT patients respectively. Results: Copy number alterations of RAD21, SMC1B, and STAG1 were observed in 18% (n = 52), 6.3% (n = 18), and 12% (n = 35) of the cohort respectively. They were predominantly losses in SMC1B, but gains in RAD21 and STAG1. All three genes in the Cohesin complex were associated with increased risk of biochemical relapse: RAD21 on chromosome 8 (HR = 1.93, 95% CI 1.23, 3.02, Wald’s p = 0.004), SMC1B on chromosome 22 (HR = 3.37, 95% CI 1.91, 5.94, Wald’s p < 10-4), and STAG1 on chromosome 3 (HR = 1.74, 95% CI 1.04, 2.89, Wald’s p < 0.05). However, when controlled for percent genome alteration and pre-treatment serum PSA levels, only copy number loss of SMC1B was a significant predictor of biochemical relapse (HR = 2.95, 95% CI 1.62, 5.38, Wald’s p < 10-3). Conclusions: We identified a novel association of copy-number alterations in members of the Cohesin complex with biochemical recurrence following radical prostatectomy or image-guided radiotherapy. This points to the central role of Cohesin in cell-cycle and DNA damage pathways promoting prostate cancer progression.

Stereotactic robotic radiosurgery for localized prostate cancer: Initial evaluation of acute toxicities

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16006-e16006
Author(s):  
L. E. Ponsky ◽  
C. Lillibridge ◽  
J. Brindle ◽  
Y. Zhang ◽  
B. Wessels ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Stage ◽  
Transrectal Ultrasound ◽  
Target Volume ◽  
Post Treatment ◽  
Intermediate Risk ◽  
Rectal Pain ◽  
Robotic Radiosurgery ◽  
Risk Prostate Cancer ◽  
Pre Treatment

e16006 Background: We evaluated the initial acute toxicities experienced by patients treated with cyberknife fractionated radiosurgery for low and low-intermediate risk prostate cancer. Methods: Twenty-two patients with low or low-intermediate risk prostate cancer (T2a, GG 3+3=6 or 3+4=7, PSA <10) were enrolled prospectively on an IRB approved protocol and treated the planning target volume (PTV)(prostate+5mm margin) with cyberknife fractionated radiosurgery to a dose of 36.25 Gy in 5 fractions (7.25Gy/fraction). The target volume included the prostate and seminal vesicles. PSA values, AUA symptom scores (AUA SS), and NCI CTC acute toxicities were analyzed prior to radiosurgery and at 1 month (N=16), 3 months (N=12) and 6 months (N=5)post-treatment. Results: Patients treated on study included 12 with GG 3+3=6 cancer and 10 with GG 3+4=7 cancer. Mean patient age was 66 years old (range 49–79). Mean pre-treatment PSA was 5.29 (range 0.64–9.36) declining to 3.44 (range 0.00–10.43) at 1 month post treatment, 1.99 (range 0.31–3.99) at 3 months post-treatment and 2.08 (1.05–3.13) at 6 months post-treatment. Mean pre-treatment AUA SS was 7 (range 0.–18) increasing to 12 (range 2–29) at 1 month post treatment, decreasing to 8 (range 2–17) at 3 months post-treatment and 11 (3–17). There were 5 grade 1 acute toxicities including (diarrhea, fatigue, mild urinary frequency, hemorrhoid and a rash) and 7 grade 2 toxicities including (bladder spasms, painful urinary, bowel irregularity, rectal pain, urethritis and numbness in the upper thigh), all grade 1 and 2 toxicities resolved within three months of treatment. The one patient with grade 2 thigh numbness was not thought to be study related toxicity. Two patients developed grade 3 toxicity. One developed bacteremia after the transrectal ultrasound guided placement of the fiducials, the infection completely resolved after treatment with antibiotics. One patient on Coumadin developed hematuria which resolved with conservative management. Conclusions: Cyberknife fractionated radiosurgery for patients with early stage prostate cancer appears to be safe on our early initial assessment.Continued evaluation and longer follow-up ongoing. [Table: see text]

Role of 5-alpha-reductase inhibitors in active surveillance of patients with low-risk prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 14-14
Author(s):  
Andrew Szehsun Chiang ◽  
D. Andrew Loblaw ◽  
Vibhuti Jethava ◽  
Perakaa Sethukavalan ◽  
Liying Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Doubling Time ◽  
Low Risk ◽  
Reductase Inhibitors ◽  
Psa Doubling Time ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer ◽  
5 Alpha Reductase Inhibitors ◽  
Doubling Times

14 Background: Active surveillance (AS) is a recognized management option for low-risk prostate cancer. Many institutions use serial PSA values to determine when to reclassify patients into higher risk categories. The impact of 5-alpha-reductase inhibitors (5-ARIs) in this setting has not been well studied. The purpose of this retrospective review was to compare PSA doubling time prior to the initiation of a 5-ARI (pre-5-ARI) to that after the PSA nadir (post-nadir) has been reached. Methods: Between 1996 and 2010, a total of 100 patients with a history of 5-ARI use were captured from our AS database. Of these, twenty-nine had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir doubling times. The majority had stage T1c disease (89.7%) and Gleason scores of six or lower (93.1%). The average PSA at presentation was 6.93 µg/L. More patients were prescribed dutasteride (79.3%) than finasteride (20.7%). PSA doubling time was calculated using the general linear mixed-model method. Statistical analysis was performed using the non-parametric sign test. Results: Median follow-up was 69.5 months (mo). For the twenty-nine patients analyzed, the median pre-5-ARI PSA doubling time was 55.8 mo (6-556.8 mo), while that for the post-nadir values was 25.2 mo (6-231 mo) (p=0.0081). Six patients were ultimately reclassified after an average of 67.7 mo (59-95 mo), due to progression in either PSA doubling time (n=2) or Gleason score (n=4). The median pre-5-ARI and post-nadir doubling times for this group were 48.2 mo (32.4-91.1 mo) and 23.3 mo (6-44.3 mo), respectively. Five of the patients underwent radical prostatectomy, while one underwent radiotherapy with androgen deprivation. Of the six patients, one had biochemical failure after an average post-treatment follow-up of 21.3 mo (0-52 mo). Conclusions: In AS for low-risk prostate cancer, it was found that 5-ARIs significantly decreased PSA doubling time. This effect may be related to preferential suppression of benign prostatic tissue, thereby providing a more accurate depiction of the true cancer-related doubling time. If validated with a larger cohort, 5-ARIs may enhance the utility of PSA doubling time as a biomarker of disease progression in AS.

Prostate specific antigen five years following stereotactic body radiation therapy (SBRT) for low and intermediate risk prostate cancer: An ablative procedure?

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 123-123
Author(s):  
Shaan Kataria ◽  
Harsha Koneru ◽  
Shan Guleria ◽  
Malika Danner ◽  
Marilyn Ayoob ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
University Hospital ◽  
High Rate ◽  
Total Testosterone ◽  
Intermediate Risk ◽  
Biochemical Relapse ◽  
Risk Prostate Cancer ◽  
Psa Nadir

123 Background: Our previous work on early PSA kinetics following prostate SBRT showed that an initial rapid and then slow PSA decline may result in very low PSA nadirs. This retrospective study sought to evaluate the PSA nadir 5 years following SBRT for low and intermediate risk prostate cancer (PCa). Methods: 65 low and 80 intermediate risk PCa patients were treated definitively with SBRT at Georgetown University Hospital between January 2008 and October 2011. All patients were treated to 35-37.5 Gy in 5 fractions delivered via the CyberKnife Radiosurgical System. Patients who received androgen deprivation therapy were excluded from this study. Pre- and post-treatment PSA and total testosterone levels were obtained during routine follow up visits. Biochemical relapse was defined as a PSA rise > 2 ng/mL above the nadir and analyzed using the Kaplan Meier method. The PSA nadir was defined as the lowest PSA value prior to biochemical relapse or as the lowest value recorded during follow up. Prostate ablation was defined as a PSA nadir < 0.2 ng/mL. Univariate logistic regression analysis was used to evaluate relevant variables on the likelihood of achieving a PSA nadir < 0.2 ng/mL. Results: The median age at the start of SBRT was 72 years. These patients had a median prostate volume of 36 cc with a median 25% of total cores involved. At a median follow up of 5.8 years, 84% and 37% of patients achieved a PSA nadir ≤ 0.5 ng/mL and < 0.2 ng/mL, respectively. Five low and 8 intermediate risk patients experienced a biochemical relapse; those who did not experience a biochemical relapse, achieved a median PSA nadir of 0.2 ng/mL. There was no difference between the 5-year bRFS rate for low (96.6%) and intermediate risk (97.4%) patients and the median time to PSA nadir was 36 months. Initial PSA (p = 0.024) and a lower testosterone at the time of the PSA nadir (p = 0.049) were found to be significant predictors of achieving a PSA nadir < 0.2 ng/mL. Conclusions: SBRT for low and intermediate risk PCa is a convenient treatment option with low PSA nadirs and a high rate of early bRFS. Less than 40% of patients achieved an ablative PSA nadir. Thus, the role of further dose escalation is an area of active investigation.

Sign in / Sign up

Export Citation Format

Share Document