Jun Kawakami

Androgen-deprivation therapy as primary treatment for localized prostate cancer: data from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE).

Prostate cancer is largely an androgen‐sensitive disease. Androgen‐deprivation therapy (ADT) generally has been used for patients with advanced disease. However, ADT is used increasingly as monotherapy for patients with clinically localized disease. The objective of the current report was to describe the characteristics of patients who underwent ADT for the management of localized disease.

Phase II study of nitric oxide donor for men with increasing prostate-specific antigen level after surgery or radiotherapy for prostate cancer.

OBJECTIVES To evaluate the effect of low-dose glyceryl trinitrate (GTN) on men with biochemical recurrence of prostate cancer after primary therapy. Preclinical, proof-of-principle studies have demonstrated that nitric oxide signaling plays a significant role in the hypoxia-induced progression of prostate cancer. METHODS A prospective, open-label clinical trial of men with an increasing prostate-specific antigen (PSA) level after surgery or radiotherapy was conducted. Men with PSA recurrence were enrolled in a 24-month trial investigating the effect of a low-dose, slow-release transdermal GTN patch. The PSA doubling time (PSADT) was compared before and after treatment initiation, as well as with a matched control group that received no immediate treatment for their PSA recurrence. RESULTS A total of 29 patients were enrolled in the study. Of the 29 patients, 62% completed the 24-month protocol, with 10% experiencing clinical disease progression. The calculated PSADT of the treatment group before initiating GTN was 13.3 months, not significantly different from that of the matched control group at 12.8 months. In an intention-to-treat analysis, the end-of-study PSADT for the treatment group was significantly different at 31.8 months (P < .001). CONCLUSIONS We report the first clinical trial of a GTN patch in patients with prostate cancer. The prolongation of the PSADT and the safety of the drug, coupled with the corresponding preclinical in vitro and in vivo data documenting the ability of nitric oxide to attenuate hypoxia-induced progression of prostate cancer, warrant further testing in a placebo-controlled study.

Incidence of infectious complications following transrectal ultrasound-guided prostate biopsy in Calgary, Alberta, Canada: A retrospective population-based analysis

INTRODUCTION We have seen an increased risk of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS-PB). Fluoroquinolone (FQ) antibiotics are common for prophylaxis prior to TRUS-PB. We evaluate whether increasing FQ resistance correlates with increased incidence of post-biopsy infectious complications at our institution. METHODS We conducted a retrospective chart and electronic health record review on 927 patients who underwent TRUS-PB between January and July of 2012 in Calgary, Alberta, Canada. We prospectively collected the following variables: age, pre-biopsy prostate-specific antigen, and date of biopsy. We documented presentation to an emergency department within 30 days of TRUS-PB for infectious and non-infectious complications. RESULTS Of the 927 patients, 58 patients (6.3%) were admitted to the emergency department due to post-TRUS-PB complications within 30 days post-biopsy. The most common infectious complications were sepsis in 21 patients (2.2%), followed by urinary tract infection (UTI) in 9 (0.9%), and prostatitis in 4 (0.4%). We found that 83% of the septic episodes and 66.6% of the UTIs were attributed to ciprofloxacin resistant Escherichia coli (E. coli). The incidence of non-infectious complications was as follows: urinary retention in 12 (1.2%), hematuria in 9 (0.9%), and rectal bleeding in 8 (0.8%). CONCLUSION Our results suggest an increased incidence of infectious complications caused by FQ resistant organisms following TRUS-PB. This finding could be attributed to increasing community resistance to ciprofloxacin. The current antimicrobial prophylactic regimen needs to be re-evaluated, and a novel approach may need to be considered.

Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists

PURPOSE We examined the serum levels of testosterone (T) (total and bioavailable) dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prostate-specific antigen (PSA) in men receiving treatment with luteinizing hormone releasing-hormone (LHRH) agonists for metastatic prostate cancer. In doing this, we want to determine the efficacy of these agents in lowering T levels and whether a possible relationship exists between PSA values, as a surrogate measure of tumour activity, and hormone levels. METHODS This was a single centre prospective study of patients on LHRH agonists. Of all the 100 eligible patients, 31 did not qualify (10 were receiving their first injection, 13 were on intermittent hormonal therapy, 7 refused to enter the trial and 1 patients blood sample was lost). Therefore in total, 69 patients were included in the final analysis. Each patient had their blood sample drawn immediately before the administration of a LHRH agonist. The new proposed criteria of <20 ng/dL (0.69 nmol/L) of total testosterone was used to define optimal levels of the hormone in this population. RESULTS Of the 69 patients, 41 were on goserelin injections, 21 on leuprolide, and 7 on buserelin. There was no statistical difference in hormone levels between any of the medications. Overall, 21% of patients failed to reach optimal levels of total testosterone. PSA levels were higher in this group. There was a statistically significant correlation between PSA and testosterone levels, as well as between PSA and FSH. Serum levels of PSA, however, did not correlate with those of bioavailable testosterone. CONCLUSIONS Failure to reach optimal levels of testosterone occurs in patients on LHRH agonist therapy. Higher PSA values are more commonly found in patients with suboptimal levels of testosterone receiving LHRH analogs, but the clinical importance of this finding has not been established. There is no significant difference with respect to hormonal levels reached among patients on a variety of LHRH agonists. Total testosterone determinations should be considered in patients on LHRH agonist therapy, particularly when the PSA values begin to rise since it may lead to further beneficial hormonal manipulation.

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience.

PURPOSE Treatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT. PATIENTS AND METHODS Six men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound-guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30Gy, received 24Gy in four fractions. RESULTS Median age was 67.5 (56-74) years. At a median followup of 26 (14-60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3-5 toxicity. CONCLUSION Transperineal ultrasound-guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.

High resolution analysis of wait times and factors affecting surgical expediency

OBJECTIVES Wait times in Canada are increasingly being monitored as an indicator of quality health care delivery. We created a higher resolution picture of the wait experienced by urological surgery patients beginning with the initial referral. In doing so, we hoped to (a) identify potential bottlenecks and common delays at our centre, and (b) identify predictors of wait time. METHODS The charts of 322 patients undergoing surgery from November 2007 to March 2008 were reviewed and specific dates, patient factors and delays were recorded. The data were used to detail the patients wait and to determine the patient factors which were predictive of wait time. RESULTS The mean time from decision to operate to the day of operation was 75.87 days for all patients. This number accounts for 53% of the wait time, while the time from referral to decision to operate is 47%. Predictors of a decreased wait time include cancer cases, younger age, urgency score, repeat patients and female gender in multivariate analysis. Delays were experienced by 16.8% of patients; most common delays were operating room cancellations/time constraints, patients requiring further optimization and delays in referral (4.7%, 3.4% and 3.1%, respectively). CONCLUSIONS The waiting process is complex; the actual waiting time that a patient must endure is much longer than the wait times traditionally recorded and reported by hospitals. As strategies are implemented to decrease wait times, it will become increasingly important to monitor the entire wait time from referral to operation and to ensure that changes are being made that truly decrease wait times and not simply shift where and when the patient waits.

Positive surgical margins during partial nephrectomy for renal cell carcinoma: Results from Canadian Kidney Cancer information system (CKCis) collaborative

INTRODUCTION We sought to determine the incidence, risk factors, and prognosis for patients with positive surgical margin (PSM) during partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS From the Canadian Kidney Cancer information system (CKCis) database, a historical cohort of PN patients with PSM were identified and compared to negative surgical margin (NSM). Risk factors for PSM were examined through multivariable logistic regression. Kaplan-Meier curves were used to compare progression-free survival. RESULTS Of 1103 patients, 972 (88.1%), 71 (6.4%), and 60 (5.4%) had NSM, PSM, and unknown status, respectively. Median patient age and tumour size were 61 years and 3.0 cm for both groups. From multivariable analysis, pathological stage ≥T3 (odds ratio [OR] 2.51; 95% confidence interval [CI] 1.13-5.60) and Fuhrman grade 4 (OR 5.35; 95% CI 1.11-25.72) were associated with PSM, whereas age, operative technique, and tumour size were not. Forty-nine (5.0%) patients from the NSM cohort and seven (9.9%) from the PSM cohort had a local/systemic progression of disease (adjusted hazard ratio [HR] 1.4; 95% CI 0.6-3.6). There were three (0.3%) cancer-related deaths in the NSM group and none in the PSM group. After median followup of 19 (interquartile range [IQR] 5-42) and 15 (IQR 7-30) months, 855 (91.4%) and 61 (89.7%) patients were alive in the NSM and PSM groups, respectively. CONCLUSIONS PSM occurred in 6.4% of PNs performed for RCC in this pan-Canadian cohort. Higher stage and grade are associated with a higher risk of positive margin. The small association between a PSM and progression suggests that complete nephrectomy is not necessary in patients with a PSM. The main study limitations are lack of nephrometry score and possible reporting bias.

Follow-up imaging after nephrectomy for cancer in Canada: urologists' compliance with guidelines. An observational study

BACKGROUND Surgical tumour removal remains the preferred treatment for most patients with renal cell carcinoma, and many medical associations have proposed guidelines for the optimal surveillance of patients following surgery. This study evaluated the adherence of Canadian urologists to the follow-up guidelines proposed by the Canadian Urological Association (CUA) in 2009. METHODS The study cohort was identified from the Canadian Kidney Cancer Information System, a prospectively populated database from 15 academic institutions in 6 Canadian provinces: British Colombia, Alberta, Manitoba, Ontario, Quebec and Nova Scotia. A total of 1982 patients who underwent radical or partial nephrectomy for stage pT1-3N0M0 renal cancer between January 2011 and June 2016 were included in the cohort. Numbers of abdominal and chest imaging tests performed during the follow-up period were captured and compared with the 2009 CUA guidelines. The level of compliance was measured by means of weighted κ and Pearson correlation statistics. Multivariate logistic regression was used to evaluate factors associated with noncompliance (under- or overtesting) in the postoperative surveillance period. RESULTS Of the 1982 patients, 1380 had stage pT1 disease, 164 had stage pT2 disease, and 438 had stage pT3 disease. There was incongruent adherence to the CUA surveillance guidelines, with a ratio of observed to recommended tests of 0.71 and 2.27 for chest and abdominal imaging, respectively. Overall, moderate correlation between observed and recommended tests was observed, with the highest value found for abdominal imaging in the pT3 group (κ = 0.59 [95% confidence interval 0.52-0.66]). Patients who underwent radical nephrectomy and those who presented with a higher stage of the disease were less likely to receive fewer chest imaging tests than recommended, and those with stage pT2 disease, those with stage pT3 disease, those with conventional clear cell renal cell carcinoma and those with a low-risk histologic type had an increased risk of undertesting. INTERPRETATION In the 6 Canadian provinces, there are large differences between guidelines and clinical practice in imaging surveillance after nephrectomy for renal cell carcinoma. Better adherence to clinical guidelines could improve optimization of health care services.