Gleason Upgrading with Time in a Large Prostate Cancer Active Surveillance Cohort.

PURPOSE: We report the percentage of patients on active surveillance who had disease pathologically upgraded and factors that predict for upgrading on surveillance biopsies. MATERIALS AND METHODS: Patients in our active surveillance database with at least 1 repeat prostate biopsy were included. Histological upgrading was defined as any increase in primary or secondary Gleason grade on repeat biopsy. Multivariate analysis was used to determine baseline and dynamic factors associated with Gleason upgrading. This information was used to develop a nomogram to predict for upgrading or treatment in patients electing for active surveillance. RESULTS: Of 862 patients in our cohort 592 had 2 or more biopsies. Median followup was 6.4 years. Of the patients 20% were intermediate risk, 0.3% were high risk and all others were low risk. During active surveillance 31.3% of cases were upgraded. On multivariate analysis clinical stage T2, higher prostate specific antigen and higher percentage of cores involved with disease at the time of diagnosis predicted for upgrading. A total of 27 cases (15% of those upgraded) were Gleason 8 or higher at upgrading, and 62% of all 114 upgraded cases went on to have active treatment. The nomogram incorporated clinical stage, age, prostate specific antigen, core positivity and Gleason score. The concordance index was 0.61. CONCLUSIONS: In this large re-biopsy cohort with medium-term followup, most cases have not been pathologically upgraded to date. A model predicting for upgrading or radical treatment was developed which could be useful in counseling patients considering active surveillance for prostate cancer.

Long-term follow-up of a large active surveillance cohort of patients with prostate cancer.

PURPOSE: Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer. PATIENTS AND METHODS: In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients. RESULTS: Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 85.0%). There were 15 deaths (1.5%) from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1% and 94.3%, respectively. An additional 13 patients (1.3%) developed metastatic disease and are alive with confirmed metastases (n = 9) or have died of other causes (n = 4). At 5, 10, and 15 years, 75.7%, 63.5%, and 55.0% of patients remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1. CONCLUSION: Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy.

BACKGROUND AND PURPOSE: Initial results of Stereotactic Ablative Body Radiotherapy (SABR) in the treatment of localized prostate cancer appear promising however long-term quality of life (QOL) outcomes and dosimetric correlates are necessary. MATERIAL AND METHODS: A phase I/II study was performed where low risk prostate cancer patients received SABR 35 Gy in 5 fractions, once weekly. Patient self-reported QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC) at baseline and q6 month up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5∗standard deviation of the baseline. Univariate and multivariate logistic regression were used to identify dosimetric predictors of MCIC. RESULTS: 84 patients were included. The median follow-up was 50.8 months (interquartile range [IQR], 44.7-56.3). 17.9%, 26.2% and 37.5% of patients reported worse QOL on follow up in the urinary, bowel and sexual domains respectively. On univariate analysis Rectal V31.8>10%, D1cc>35 Gy were associated with bowel MCIC, penile bulb (PB) V35>4%, V20>40% with sexual MCIC. Of these factors only rectal D1cc and PB V35 were predictors of worse QOL on multivariate analysis. CONCLUSIONS: Long-term single-institution QOL outcomes are encouraging. Rigorous dosimetric constraints are needed to keep bothersome side effects low.

Improved wait time intervals for prostate cancer patients in a multidisciplinary rapid diagnostic unit compared to a community-based referral pattern.

BACKGROUND: Wait times in cancer diagnosis and treatment may significantly affect a patient's treatment outcome, prognosis and quality of life. The purpose of this study was to capture wait time intervals for patients with prostate cancer treated with radiotherapy (RT) at the Odette Cancer Centre, Toronto, Ontario, Canada and to compare patients diagnosed in a rapid diagnostic unit (RDU) versus the usual community referral process. METHODS: Patients agreed to participate in the study during their RT planning sessions. A semi-structured interview and chart abstraction was conducted to record key wait time milestones. RESULTS: A total of 87 patients participated in the study: 44 RDU patients and 43 community patients. The median overall wait time intervals from suspicion of prostate cancer to RT was 138 and 183 days, respectively (p = 0.046). There were statistically significant differences observed for other key wait time intervals favouring the RDU cohort: suspicion to decision-to-treat (DTT; p = 0.012), urologist visit to diagnosis (p = 0.0094), diagnosis to DTT (p = 0.018), and diagnosis to treatment (p = 0.016). Risk category and Gleason sum was independently predictive of longer intervals from diagnosis to DTT. INTERPRETATION: Wait time intervals from suspicion to treatment are significantly shorter for prostate cancer patients in 2011 to 2012 than in 2003 when patients were diagnosed and referred in the community setting. A prostate-specific RDU further reduced a number of key wait time intervals supporting more multidisciplinary RDUs for common diseases. Further work needs to be done to identify why delays are occurring and to develop new processes to minimize delays.

A prospective study on pain score with transperineal prostatic gold seed fiducial implantation under local anesthetic alone.

BACKGROUND: The purpose of this study was to monitor patient pain score with transperineal prostatic gold seed implantation in the absence of conscious sedation. METHODS: All patients who were scheduled for image-guided external beam radiation (IGRT) and referred for gold seed fiducials were eligible to participate. Gold seed implants were performed by two radiation oncologists between December 2007 and April 2008. Patients received only local and deep anesthetic. No patients had prophylactic IV cannulation for the procedure. Three gold seeds were inserted transperineally into the prostate. A visual analogue scale from 0 to 10 was used to assess the pain at baseline, local and deep anesthetic infiltration, with each seed drop, and after the completion of the procedure. RESULTS: A total of 30 patients were accrued to this study. The highest recorded increase in pain score was at the time point of deep local anesthesia, at which the mean pain score was 3.8. The mean pain scores at each seed drop were 0.8 (standard deviation [SD]=1.24), 1 (SD=1.26), and 0.5 (SD=0.90), respectively. All gold seed insertion procedures were well-tolerated, with no patients having significant pain post-procedure, and no significant procedural complications. There were only slight increases in dysuria, urinary frequency, constipation, urinary retention and flatulence in 7 patients - none of which required intervention. INTERPRETATION: Transperineal ultrasound-guided gold seed implantation without conscious sedation is well-tolerated and associated with a low complication rate. It is a convenient outpatient procedure obviating the need for resource intensive postoperative monitoring.

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer.

INTRODUCTION: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alpha-reductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourable-risk prostate cancer. METHODS: Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. RESULTS: The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. CONCLUSION: 5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancer-related DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.

Patient costs associated with external beam radiotherapy treatment for localized prostate cancer: the benefits of hypofractionated over conventionally fractionated radiotherapy.

INTRODUCTION: To estimate the out-of-pocket costs for patients undergoing external beam radiotherapy (EBRT) for prostate cancer and calculate the patient-related savings of being treated with a 5-fraction versus a standard 39-fraction approach. MATERIALS AND METHODS: Seventy patients accrued to the pHART3 (n = 84) study were analyzed for out-of-pocket patient costs as a result of undergoing treatment. All costs are in Canadian dollars. Using the postal code of the patient's residence, the distance between the hospital and patient home was found using Google Maps. The Canada Revenue Agency automobile allowance rate was then applied to determine the cost per kilometer driven. RESULTS: The average cost of travel from the hospital and pHART3 patient's residence was $246 per person after five trips. In a standard fractionation regimen, pHART3 patients would have incurred an average cost of $1921 after 39 visits. The patients receiving hypofractionated radiotherapy would have paid an average of $38 in parking while those receiving conventional treatment would have paid $293. The difference in out-of-pocket costs for the patients receiving a standard versus hypofractionated treatment was $1930. CONCLUSIONS: Medium term prospective data shows that hypofractionated radiotherapy is an effective treatment method for localized prostate cancer. Compared to standard EBRT, hypofractionated radiotherapy requires significantly fewer visits. Due to the long distance patients may have to travel to the cancer center and the expense of parking, the short course treatment saves each patient an average of $1900. A randomized study of standard versus hypofractionated accelerated radiotherapy should be conducted to confirm a favorable efficacy and tolerability profile of the shorter fractionation scheme.