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1.  Real-time individual predictions of prostate cancer recurrence using joint models 
Biometrics  2013;69(1):206-213.
Summary
Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this paper, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2,386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient.
doi:10.1111/j.1541-0420.2012.01823.x
PMCID: PMC3622120  PMID: 23379600
Joint longitudinal-survival model; Online calculator; Predicted probability; Prostate cancer; PSA
2.  Canadian prostate brachytherapy in 2012 
Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy.
doi:10.5489/cuaj.218
PMCID: PMC3650818  PMID: 23671495
3.  Pre-treatment risk stratification of prostate cancer patients: A critical review 
Introduction:
The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems.
Methods:
A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema.
Results:
The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and high-intermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors.
Conclusions:
Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.
doi:10.5489/cuaj.11085
PMCID: PMC3328553  PMID: 22511420
4.  The need for, and utilization of prostate-bed radiotherapy after radical prostatectomy for patients with prostate cancer in British Columbia 
Introduction:
Three randomized trials have demonstrated that post-radical prostatectomy (RP) radiotherapy decreases biochemical relapse for those with adverse pathology. Our purpose was to describe the incidence of pathologic risk factors for recurrence in a contemporary series of patients treated with RP and to describe the use of post-RP radiotherapy.
Methods:
All incident prostate cancers diagnosed between January 2005 and December 2007 were identified from the tumour registry. Cases were then linked to radiotherapy records which included dose and modality (external beam radiotherapy and brachytherapy). The pathology reports in the tumour registry were reviewed for pathologic stage, grade and margin status.
Results:
We identified 9223 patients with prostate cancer. Overall, 36.3% of patients treated with RP had positive margins, and may have benefited from adjuvant radiotherapy. After RP, 332 (15%) patients had radiotherapy to the prostate bed; of these, only 25 (1.1%) received truly adjuvant radiotherapy (delivered within 6 months with a prostate-specific antigen of <0.2 ng/mL). Of the 2181 patients treated with RP, 270 (12%) were seen by a radiation oncologist within 6 months of RP. Of the 1015 patients (47%) with adverse RP pathology (positive margins, extracapsular extension or seminal vesicle invasion), 230 (23%) were seen by a radiation oncologist within 6 months of RP.
Conclusion:
Not all patients with adverse prostatectomy pathology were seen by a radiation oncologist post-prostatectomy, and very few received adjuvant radiotherapy despite almost half of them having risk factors for relapse.
doi:10.5489/cuaj.11158
PMCID: PMC3328560  PMID: 22511413
5.  Randomized study evaluating testosterone recovery using short-versus long-acting luteinizing hormone releasing hormone agonists 
Introduction:
We sought to compare the rate of return of testosterone levels and sexual function in men with prostate cancer receiving longer acting, 3-month preparation of luteinizing hormone-releasing hormone agonist (L-LHRH-A) versus shorter acting, 1-month preparation of luteinizing hormone-releasing hormone agonist (S-LHRH-A).
Methods and Materials:
Men with low to intermediate risk localized prostate cancer were randomized to either L-LHRH-A (2–3 month duration LHRH-A) or S-LHRH-A (6-1 month duration LHRH-A) of androgen suppression therapy (AST) and prostate brachytherapy using iodine-125 radioisotopes. Serum total testosterone levels and PSA were recorded every 2 months for 2 years.
Results:
A planned target sample size of 100 was not achieved due to insufficient accrual. A total of 55 patients were randomized and 46 were used for analysis. The median time to recovery of testosterone to baseline levels (calculated from end of AST) was 8 and 4 months in the L-LHRH-A and S-LHRH-A arms, respectively (p = 0.268). The median time to testosterone recovery to lower limit of reference range was 4 and 2 months respectively (p = 0.087).
Interpretation:
This randomized study, which failed to reach accrual target, showed a trend towards more rapid recovery of testosterone levels using shorter acting LHRH-A. Another randomized study would be required to validate these findings. Currently, there is insufficient evidence to recommend the use of shorter acting LHRH-A as a means of providing more rapid recovery of testosterone levels.
doi:10.5489/cuaj.10102
PMCID: PMC3114026  PMID: 21672478
6.  Hormone use after radiotherapy failure: a survey of Canadian uro-oncology specialists 
Introduction:
A survey of Canadian uro-oncology specialists was performed to assess practice patterns of patients with recurrent prostate cancer postradiotherapy and to assess the feasibility of conducting a trial in this setting.
Methods:
There were 14 survey questions and 1 demographic question. Responses were reported by frequency.
Results:
There were 96 respondents. Most respondents use both prostate-specific antigen doubling time (PSAdt) and PSA level when deciding to start androgen deprivation therapy (ADT) in asymptomatic patients. About half of respondents start ADT when PSA is greater than 10 ng/mL or when the PSAdt is less than 6 months. Eighty-six percent felt that the timing of ADT was an important research question. Over 1500 patients per year were estimated as being available for such a trial.
Conclusion:
After radiotherapy failure, respondents initiated ADT about half of the time when PSA is less than 10 ng/mL and/or PSAdt is less than 6 months. A clinical trial examining the timing of ADT has strong support and appears to be feasible.
PMCID: PMC2792430  PMID: 20019973
7.  Salvage radiotherapy following biochemical relapse after radical prostatectomy: proceedings of the Genito-Urinary Radiation Oncologists of Canada consensus meeting 
For patients with recurrent prostate cancer after radical prostatectomy, salvage radiotherapy is the only potentially curative treatment option. However, until recently there has been a paucity of data on the effectiveness of this approach. In light of recently published studies, the Genito-Urinary Radiation Oncologists of Canada (GUROC) met and crafted a consensus statement regarding the current place of salvage radiotherapy. GUROC also identified gaps in current knowledge and identified ongoing study protocols that will advance our knowledge in this area.
This report summarizes the main conclusions of the meeting and the commentary provided during the consensus-building process, and outlines the consensus statement that was subsequently adopted.
PMCID: PMC2572238  PMID: 18953445
8.  Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy 
Purpose
To assess whether an expanded (five level) risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT).
Materials and methods
Using a previously validated 5-risk group schema, a prospective non-randomized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control (bNED) with the RTOG-ASTRO "Phoenix" definition (lowest PSA to date + 2 ng/mL), both with and without adjuvant ADT. The median follow-up was 5 years.
Results
There was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate, high and extreme risk groups. The 5-year bNED rates with and without ADT were 70% and 73% respectively for the low intermediate group (p = non-significant) and 72% and 58% respectively for the high intermediate group (p = 0.002).
Conclusion
There appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less. ADT is beneficial in patients treated to standard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher.
doi:10.1186/1748-717X-3-8
PMCID: PMC2358899  PMID: 18423030
9.  Adjuvant radiotherapy following radical prostatectomy: Genito-Urinary Radiation Oncologists of Canada Consensus Statement 
Until the results of 3 randomized trials became known in 2005, the role of adjuvant postoperative radiation therapy following radical prostatectomy was poorly defined. After the publication of these trials, the Genito-Urinary Radiation Oncologists of Canada (GUROC) met and crafted a consensus statement regarding the current place of adjuvant radiation therapy. GUROC also identified gaps in current knowledge and strongly supports ongoing study protocols to further quantify the benefit of postoperative radiotherapy.
This report summarizes the main trial findings and the commentary provided during the consensus-building process. It also outlines the subsequent consensus statement.
PMCID: PMC2422905  PMID: 18542740
10.  The median non-prostate cancer survival is more than 10 years for men up to age 80 years who are selected and receive curative radiation treatment for prostate cancer 
Treatment guidelines recommend that curative radiation treatment of prostate cancer be offered only to men whose life expectancy is greater than 10 years. The average life expectancy of North American males is less than 10 years after age 75, yet many men older than 75 years receive curative radiation treatment for prostate cancer. This study used the provincial cancer registry in British Columbia, Canada, to determine median non-prostate cancer survival for men who were aged 75 to 82 years at start of radiation treatment. Median survival was found to be greater than 10 years in men aged up to 80 years at the start of their radiation treatment. This finding suggests that radiation oncologists are able to appropriately select elderly men with greater than average life expectancy to receive curative radiation treatment.
doi:10.1186/1748-717X-2-17
PMCID: PMC1887532  PMID: 17511871
11.  What's a man to do? Treatment options for localized prostate cancer. 
Canadian Family Physician  2004;50:65-72.
OBJECTIVE: To describe treatments for localized prostate cancer: surgery, external radiation therapy, and brachytherapy; watchful waiting might also be appropriate. Patients trying to decide about treatment ask family physicians for advice. This article sets out a framework to aid patients (and physicians) in the decision. QUALITY OF EVIDENCE: Only two randomized studies comparing different treatments were identified. Because of the paucity of level I or II evidence, suggestions in this review are largely based on expert opinion and consensus statements. MAIN MESSAGE Risk-grouping and nomograms are useful for assessing treatments and estimating outcomes of treatment. Where treatments are equivalent, decisions can be based on perception of toxicity and convenience. Effects on patients'lives and on sexual, urinary, and bowel function vary by treatment modality. CONCLUSION: Men with low-risk prostate cancer should decide on treatment based on their perception of how treatment will affect their lives. Men with higher-risk cancers might accept adverse effects on their quality of life in return for longer survival.
PMCID: PMC2214501  PMID: 14761106
12.  Current status of PSA screening. Early detection of prostate cancer. 
Canadian Family Physician  2004;50:57-63.
OBJECTIVE: To update current evidence for prostate-specific antigen (PSA) screening for prostate cancer and to give readers some practical information to discuss with patients. QUALITY OF EVIDENCE A MEDLINE: search revealed only three randomized studies, two of which are incomplete. Several controlled non-randomized studies were found. MAIN MESSAGE: Two ongoing studies have not yet reported survival data, but have added to evidence for screening intervals. One Canadian randomized study has been criticized for its design and conclusions. Non-randomized studies suggest that screening effectively identifies serious cancers and leads to earlier diagnosis. Mortality from prostate cancer has been falling in most western countries since 1992. This cannot be explained by PSA screening, which would probably not produce survival benefit until at least 10 years after its unofficial introduction in about 1990. CONCLUSION: Indirect evidence suggests that all men older than 45 with at least a 10-year life expectancy should be informed of the potential benefits and drawbacks of PSA screening so they can make an informed decision on whether to have the test.
PMCID: PMC2214499  PMID: 14761105

Results 1-12 (12)