Ronald T. Kodama

Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study

BACKGROUND Studies of complications resulting from surgery or radiotherapy for prostate cancer have mainly focused on incontinence and erectile dysfunction. We aimed to assess other important complications associated with these treatments for prostate cancer. METHODS We did a population-based retrospective cohort study, in which we used administrative hospital data, physician billing codes, and cancer registry data for men who underwent either surgery or radiotherapy alone for prostate cancer between 2002 and 2009 in Ontario, Canada. We measured the 5-year cumulative incidence of five treatment-related complication endpoints: hospital admissions; urological, rectal, or anal procedures; open surgical procedures; and secondary malignancies. FINDINGS In the 32 465 patients included in the study, the 5-year cumulative incidence of admission to hospital for a treatment-related complication was 22·2% (95% CI 21·7-22·7), but was 2·4% (2·2-2·6) for patients whose length of stay was longer than 1 day. The 5-year cumulative incidence of needing a urological procedure was 32·0% (95% CI 31·4-32·5), that of a rectal or anal procedure was 13·7% (13·3-14·1), and that of an open surgical procedure was 0·9% (0·8-1·1). The 5-year cumulative incidence of a second primary malignancy was 3·0% (2·6-3·5). These risks were significantly higher than were those of 32 465 matched controls with no history of prostate cancer. Older age and comorbidity at the time of index treatment were important predictors for a complication in all outcome categories, but the type of treatment received was the strongest predictor for complications. Patients who were given radiotherapy had higher incidence of complications for hospital admissions, rectal or anal procedures, open surgical procedures, and secondary malignancies at 5 years than did those who underwent surgery (adjusted hazard ratios 2·08-10·8, p<0·0001). However, the number of urological procedures was lower in the radiotherapy than in the surgery group (adjusted hazard ratio 0·66, 95% CI 0·63-0·69; p<0·0001) INTERPRETATION: Complications after prostate cancer treatment are frequent and dependent on age, comorbidity, and the type of treatment. Patients and physicians should be aware of these risks when choosing treatment for prostate cancer, and should balance them with the clinical effectiveness of each therapy. FUNDING Ajmera Family Chair in Urologic Oncology.

Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis

Objective To determine the association between exposure to radiotherapy for the treatment of prostate cancer and subsequent second malignancies (second primary cancers). Design Systematic review and meta-analysis of observational studies. Data sources Medline and Embase up to 6 April 2015 with no restrictions on year or language. Study selection Comparative studies assessing the risk of second malignancies in patients exposed or unexposed to radiotherapy in the course of treatment for prostate cancer were selected by two reviewers independently with any disagreement resolved by consensus. Data extraction and synthesis Two reviewers independently extracted study characteristics and outcomes. Risk of bias was assessed with the Newcastle-Ottawa scale. Outcomes were synthesized with random effects models and Mantel-Haenszel weighting. Unadjusted odds ratios and multivariable adjusted hazard ratios, when available, were pooled. Main outcome measures Second cancers of the bladder, colorectal tract, rectum, lung, and hematologic system. Results Of 3056 references retrieved, 21 studies were selected for analysis. Most included studies were large multi-institutional reports but had moderate risk of bias. The most common type of radiotherapy was external beam; 13 studies used patients treated with surgery as controls and eight used patients who did not undergo radiotherapy as controls. The length of follow-up among studies varied. There was increased risk of cancers of the bladder (four studies; adjusted hazard ratio 1.67, 95% confidence interval 1.55 to 1.80), colorectum (three studies; 1.79, 1.34 to 2.38), and rectum (three studies; 1.79, 1.34 to 2.38), but not cancers of the hematologic system (one study; 1.64, 0.90 to 2.99) or lung (two studies; 1.45, 0.70 to 3.01), after radiotherapy compared with the risk in those unexposed to radiotherapy. The odds of a second cancer varied depending on type of radiotherapy: treatment with external beam radiotherapy was consistently associated with increased odds while brachytherapy was not. Among the patients who underwent radiotherapy, from individual studies, the highest absolute rates reported for bladder, colorectal, and rectal cancers were 3.8%, 4.2%, and 1.2%, respectively, while the lowest reported rates were 0.1%, 0.3%, and 0.3%. Conclusion Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low. Further studies with longer follow-up are required to confirm these findings.

Population Based Study of Long-Term Rates of Surgery for Urinary Incontinence After Radical Prostatectomy for Prostate Cancer

PURPOSE Urinary incontinence can be a significant complication of radical prostatectomy. It can be treated with post-prostatectomy surgical procedures. The long-term rate of patients who undergo these surgeries, including artificial urinary sphincter or urethral sling insertion, is not well described. We examined the long-term rate of post-prostatectomy incontinence surgery and factors influencing it. MATERIALS AND METHODS We performed a population based study of 25,346 men who underwent radical prostatectomy for prostate cancer in Ontario, Canada between 1993 and 2006. We used hospital and cancer registry administrative data to identify patients from this cohort who were later treated with surgery for urinary incontinence. RESULTS Of the 25,346 patients 703 (2.8%) underwent artificial urinary sphincter insertion and 282 (1.1%) underwent urethral sling placement a median of 2.9 years after prostatectomy. The probability of an artificial urinary sphincter/sling procedure increased with time from prostatectomy. Cumulative 5, 10 and 15-year Kaplan-Meier rates of an artificial urinary sphincter/sling procedure were 2.6% (95% CI 2.4-2.8), 3.8% (95% CI 3.6-4.1) and 4.8% (95% CI 4.4-5.3), respectively. Factors predicting surgery for incontinence were patient age at radical prostatectomy (HR 1.24 per decade, 95% CI 1.11-1.38, p = 0.0002), radiotherapy after surgery (HR 1.61, 95% CI 1.36-1.90, p <0.0001) and surgeon volume (49 or greater prostatectomies per year) (HR 0.59, 95% CI 0.46-0.77, p <0.0001). CONCLUSIONS Of patients who undergo radical prostatectomy 5% are expected to be treated with surgery for urinary incontinence during a 15-year period. Increasing patient age, radiation treatment and low surgeon volume are associated with significantly higher risk.

Traumatic Intimal Tear of the Renal Artery Treated by Insertion of a Palmaz Stent

A renal artery intimal injury induced by blunt trauma in a 23-year-old man was treated by percutaneous placement of a Palmaz endovascular stent. The patient was placed on anticoagulation for 2 months following stent insertion. Nuclide renal scans demonstrated recovery of normal renal function on the affected side at 9 months postprocedure.

Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer

Background:Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life.Methods:On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data.Results:Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6–4.7, P=0.002 to <0.0001).Conclusions:In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.

Complications after radical prostatectomy or radiotherapy for prostate cancer: results of a population-based, propensity score-matched analysis.

OBJECTIVE To assess rates of treatment-related complications after radical prostatectomy or radiotherapy monotherapy, using propensity score matching to account for baseline differences between these patient populations. METHODS On the basis of a population-based study of men undergoing surgery or radiotherapy for prostate cancer in Ontario between 2002 and 2009, we undertook a propensity score-matched analysis including age, comorbidity, and year of treatment to assess treatment-related complication end points. These included hospital admission; urologic, rectal, or anal procedures; open surgeries; and secondary malignancies. RESULTS From the original cohort of 32,465 patients, 15,870 (48.9%) had surgery and 16,595 (51.1%) had radiation. Propensity score matching produced 8797 pairs (17,594 patients). Among these, when compared with patients treated with surgery, those treated with radiation experienced fewer admissions to hospital (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.78-0.92) and urologic procedures (HR, 0.50; 95% CI, 0.46-0.53) at year 1 but higher rates at year 3 (HR, 5.65; 95% CI, 4.61-6.91 and HR, 1.86; 95% CI, 1.62-2.13, respectively) and year 5. Although there was no significant difference in open surgeries at year 1, patients undergoing radiotherapy were at higher risk by year 3 (HR, 2.06; 95% CI, 1.23-3.47) and this rose by year 5. Over the study period, patients undergoing radiotherapy experienced more rectal-anal procedures (HR, 2.64; 95% CI, 2.37-2.95) and were diagnosed with more secondary malignancies (HR, 2.44; 95% CI, 1.16-5.14). Direct matching produced similar results. CONCLUSION From a propensity score-matched analysis, we found that patients undergoing radiation therapy for prostate cancer had higher rates of long-term complications in all 5 categories studied than patients undergoing surgery.

A Prospective Study Examining the Incidence of Bacteriuria and Urinary Tract Infection After Shock Wave Lithotripsy with Targeted Antibiotic Prophylaxis

PURPOSE Controversy exists regarding antibiotic prophylaxis before shock wave lithotripsy. The AUA (American Urological Association) guideline recommends universal antibiotic prophylaxis, whereas the EAU (European Association of Urology) guideline recommends prophylaxis only for select patients. We evaluated the use of targeted antibiotic prophylaxis in preventing urinary tract infections in patients undergoing shock wave lithotripsy. MATERIALS AND METHODS A prospective single cohort study was performed during 6 months with patients undergoing shock wave lithotripsy. All patients underwent urine dipstick and culture before shock wave lithotripsy. Targeted antibiotic prophylaxis was provided at the discretion of the treating urologist. All patients had a urine culture performed after shock wave lithotripsy and completed a survey documenting fevers or urinary symptoms. The primary outcome was the incidence of urinary tract infections, urosepsis and asymptomatic bacteriuria after shock wave lithotripsy. The secondary outcome was the sensitivity and specificity of urinary dipstick leukocytes and nitrites. RESULTS A total of 526 patients were enrolled in the study. Of the 389 patients included in the determination of the primary outcome, urinary tract infection developed in only 1 (0.3%), urosepsis did not develop in any patients and asymptomatic bacteriuria developed in 11 (2.8%). Eight (2.1%) patients were administered antibiotic prophylaxis. The specificity of urine dipstick nitrites was high (95%) while the sensitivity was poor (9.7%). CONCLUSIONS In our cohort study using targeted antibiotic prophylaxis the rates of urinary tract infection after shock wave lithotripsy and rates of asymptomatic bacteriuria were extremely low, with no development of urosepsis. This finding questions the need for universal antibiotic prophylaxis before shock wave lithotripsy.

Effect of radical prostatectomy surgeon volume on complication rates from a large population-based cohort

INTRODUCTION Surgical volume can affect several outcomes following radical prostatectomy (RP). We examined if surgical volume was associated with novel categories of treatment-related complications following RP. METHODS We examined a population-based cohort of men treated with RP in Ontario, Canada between 2002 and 2009. We used Cox proportional hazard modeling to examine the effect of physician, hospital and patient demographic factors on rates of treatment-related hospital admissions, urologic procedures, and open surgeries. RESULTS Over the study interval, 15 870 men were treated with RP. A total of 196 surgeons performed a median of 15 cases per year (range: 1-131). Patients treated by surgeons in the highest quartile of annual case volume (>39/year) had a lower risk of hospital admission (hazard ratio [HR]=0.54, 95% CI 0.47-0.61) and urologic procedures (HR=0.69, 95% CI 0.64-0.75), but not open surgeries (HR=0.83, 95% CI 0.47-1.45) than patients treated by surgeons in the lowest quartile (<15/year). Treatment at an academic hospital was associated with a decreased risk of hospitalization (HR=0.75, 95% CI 0.67-0.83), but not of urologic procedures (HR=0.94, 95% CI 0.88-1.01) or open surgeries (HR=0.87, 95% CI 0.54-1.39). There was no significant trend in any of the outcomes by population density. CONCLUSIONS The annual case volume of the treating surgeon significantly affects a patients risk of requiring hospitalization or urologic procedures (excluding open surgeries) to manage treatment-related complications.

New Rates of Interventions to Manage Complications of Modern Prostate Cancer Treatment in Older Men

BACKGROUND Interventions to treat complications from prostate cancer (PCa) treatment are common and affect the course of a patients life. OBJECTIVE To examine rates of complications other than urinary incontinence and impotence for older patients treated for PCa. DESIGN, SETTING, AND PARTICIPANTS Population-based retrospective cohort study of patients aged 65-79 yr receiving radical prostatectomy or radiotherapy (RT) from 2001 to 2008 in the US Surveillance Epidemiology and End Results and Medicare linked databases. OUTCOME MEASURES AND STATISTICAL ANALYSIS Complications were organised in three categories: urologic procedures, rectal-anal procedures, and major surgeries. We analysed the role of primary treatment on the number of complications using negative binomial regression. RESULTS AND LIMITATIONS Among 60476 men, 14492 underwent primary surgery and 45984 underwent primary RT; 33418 (55%) experienced at least one complication (mean: 2.6 complications per patient). For both groups, complications peaked within 2 yr of treatment but continued at a steady rate for 10 yr. Patients treated with radiation had higher rates of urologic procedures (adjusted relative rate [aRR]: 1.25; 95% confidence interval [CI], 1.2-1.3; p<0.0001) and rectal-anal procedures (aRR: 1.4; 95% CI, 1.4-1.5; p<0.0001) but a lower rate of major surgeries (aRR: 0.9; 95% CI, 0.8-0.9; p<0.0001) compared with those having surgery. Because patients treated with RT were older and more comorbid, selection bias limits the strength of conclusions that can be drawn from this data. CONCLUSIONS Complications are common following PCa cancer treatment and occur many years after treatment. The primary treatment is an important predictor of complication rates that may inform treatment decisions and long-term survivorship plans. PATIENT SUMMARY We examined complications after prostate cancer treatment in a large American population. Patients treated with radiotherapy rather than surgery had higher rates of complications requiring urologic procedures and rectal-anal procedures but lower rates of open surgeries. However, we were only able to examine men aged >65 yr, and this, along with the observational study technique, means that these results may not apply to all patients and that factors beyond those that we could measure may have affected these results.

Cardiovascular and Skeletal-related Events Following Localized Prostate Cancer Treatment: Role of Surgery, Radiotherapy, and Androgen Deprivation.

OBJECTIVE To examine the impact of androgen deprivation therapy (ADT) and primary treatment modality on cardiovascular and skeletal-related events and to investigate potential effect modification in a contemporary cohort of patients treated for clinically localized prostate cancer. SUBJECTS AND METHODS We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare linked databases for men aged 65-79 years who underwent radical prostatectomy or radiotherapy for cT1 or cT2 prostate cancer from 2000 to 2008. We categorized treatment according to primary therapy and receipt of ADT. We described the cumulative incidence of cardiovascular and skeletal-related events. RESULTS Among 60,156 men, 14,403 underwent surgery and 45,753 underwent radiotherapy. Median follow-up was 6.0 years. After adjusting for baseline differences, treatments with radiotherapy (adjusted hazard ratios [aHR] 1.16-1.28, P <.0001-.04) and ADT (aHR 1.18-1.32, P <.0001-.008) were each independently associated with increased risk of coronary heart disease, sudden cardiac death, fracture, and fracture requiring hospitalization. Radiotherapy was associated with an increased risk of myocardial infarction (aHR 1.20, P = .02), whereas ADT was not (P = .5). We did not identify a significant statistical interaction between primary and hormonal treatment. CONCLUSION Care for cardiovascular and skeletal-related events is an important part of the survivorship phase for a significant proportion of patients with localized prostate cancer. Increasing use of ADT for patients with localized disease undergoing radiotherapy and the observed higher prevalence of these events in these patients should be considered when discussing the risks and benefits of treatment for localized prostate cancer and when formulating a survivorship plan.