Comparison of salvage radical prostatectomy vs. salvage ablation therapy for biopsy-proven radio-recurrent localized prostate cancer.

INTRODUCTION: Radiation therapy for prostate cancer is associated with a 15-20% five-year recurrence rate. Patients with recurrence in the prostate only are candidates for salvage local therapies; however, there is no consensus on modality. This study uses registries at Memorial Sloan Kettering Cancer Center (MSKCC) and University of Western Ontario (UWO) to compare the oncologic outcomes of salvage radical prostatectomy (SRP) and salvage ablation (SA). METHODS: A total of 444 patients were available for analysis. Due to intergroup differences, propensity score methodology was used and identified 378 patients with more comparable pre-salvage prostate-specific antigen (PSA), Gleason score, and primary radiation treatment. Patients underwent SRP at MSKCC and SA at UWO. RESULTS: Of the 378 patients, 48 died of disease, with a 6.0-year median (interquartile range [IQR] 3.0, 9.7) followup among survivors; 88 developed metastases, with a median 4.6-year (IQR 2.3, 7.9) followup among metastasis-free survivors. There was a non-significantly higher rate of cancer-specific (hazard ratio [HR ] 1.02, 95% confidence interval [CI] 0.51, 2.06, p=0.9) and improved metastasis-free survival (HR 0.71, 95% CI 0.44, 1.13, p=0.15) among patients undergoing SA compared to patients undergoing SRP. There were 143 patients who received hormonal therapy, with higher rates of androgen deprivation therapy (ADT) in SA (HR 1.42, 95% CI 0.97, 2.08, p=0.068), although this did not meet conventional levels of significance. CONCLUSIONS: This propensity score analysis of salvage therapy for radio-recurrent prostate cancer identified no statistically significant differences in oncologic outcome between SRP and SA; however, there was evidence of a lower risk of ADT in the cohort undergoing SRP. Given they are both potentially curative therapies, these treatments are viable options for men with clinically localized, radio-recurrent prostate cancer rather than ADT alone. Future research may further elucidate subpopulations that may be more amenable to either SRP or SA.

Beware the retracted testis: A novel case of metastatic goblet cell cancer causing testicular retraction.

Spontaneous retraction of the testes is a rare, underreported, and under-described phenomenon. Our case describes a 58-year-old man with spontaneous retraction and constriction of his right testis. After an acute orchidectomy was performed secondary to pain, histology revealed metastatic goblet cell cancer. This is the first ever recorded case in the medical literature and is a truly rare and novel differential for the spontaneously retracted testis.

The Interactive Relationship Between Instructor Perceptions and Learner Personality on Surgical Skills Performance.

OBJECTIVE: The objective of this study was to examine the association between learner personality and capacity to be trained (i.e., performance improvement) on a surgical task, and how instructor perceptions of the learners' capacity to be trained interact with learner personality and performance during training and feedback. There is meaningful heterogeneity in the degree of learner surgical skills acquisition despite receiving the same amount of training. While learner personality may independently contribute to skill acquisition, the instructor-learner feedback process is also important to consider. To better understand this interpersonal relationship, it is necessary to also consider instructor factors (i.e., perceptions), and how this may contribute to learner variability in skills training. DESIGN: This exploratory study employed a prospective two-phase design. Medical and non-medical undergraduate students (N = 62) completed measures of personality and participated in two 20-minute training sessions with expert feedback 2 weeks apart, performing an end-to-side anastomosis on a low-fidelity model. Learner performance and instructors' perceptions of a learner's capacity to be trained were assessed. PARTICIPANTS: Sixty-two medical and non-medical undergraduate students. RESULTS: There was a significant interaction between learner Extraversion and instructor's perceptions of learner capacity to be trained. Higher learner Extraversion was only associated with an increase in performance improvement for those who were considered trainable (OR = 4.83, p = 0.017). Post hoc analysis revealed a significant difference in the amount of feedback provided to participants who were considered trainable (M = 9.45) versus not trainable (M = 16.48). CONCLUSIONS: This study highlights the importance of both individual learner factors and instructor perceptions on surgical skill acquisition.

Long-Term Outcomes of Whole Gland Salvage Cryotherapy for Locally Recurrent Prostate Cancer following Radiation Therapy: A Combined Analysis of Two Centers.

PURPOSE: Radiation refractory prostate cancer (RRPCa) is common and salvage cryotherapy for RRPCa is emerging as a viable local treatment option. However, there is a paucity of long-term data. The purpose of this study is to determine long-term outcomes following salvage cryotherapy for RRPca. MATERIALS AND METHODS: Patients undergoing salvage cryotherapy for biopsy-proven, localized RRPCa from 1992 through 2004 were prospectively accrued at two centers. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from our database. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). The secondary outcomes were freedom from castration-resistant prostate cancer (CRPC) and freedom from androgen deprivation therapy (ADT). RESULTS: A total of 268 patients were identified with a median followup of 10.3 years. A total of 223 complication events were recorded; of them, 168 were Clavien I-II events and 55 Clavien III events. At 10 years, 69% had freedom from ADT and 76% had freedom from CRPC. The 10-year DSS rate was 81%, and the 10-year OS rate was 77%. A pre-salvage prostate specific antigen level of >10 ng/ml was associated with an increased risk of developing CRPC and initiation of ADT but was not associated with DSS or OS. The use of neoadjuvant ADT was associated with improved OS and DSS but did not affect freedom from CRPC or adjuvant ADT. CONCLUSIONS: Salvage cryotherapy for RRPCa provides excellent long-term freedom from ADT, CRPC and DSS with acceptable morbidity. OS at 10 years was 77%. Prospective trials are required for validation.

A Randomized Controlled Trial of a Modified Cystoscopy Technique using the Peak-End Rule in order to Improve Pain and Anxiety.

OBJECTIVE: To determine if a modified cystoscopy technique utilizing the peak-end rule cognitive bias decreases pain and anxiety during flexible cystoscopy in patients who undergo cystoscopy. METHODS: A total of 85 participants undergoing their first diagnostic cystoscopy were enrolled in a blinded single-center, prospective, randomized controlled trial. Patients with lower urinary tract abnormalities, prior radiation and chronic pelvic pain were excluded. Participants were randomized to a standard cystoscopy (arm A) or a modified cystoscopy (arm B) where a two-minute period at the end of the procedure was completed during which the cystoscope was left in the bladder without being manipulated. Following the cystoscopy, participants completed a standard pain and anxiety questionnaire. Differences in mean pain and anxiety score between arms were evaluated using a Mann-Whitney test with a two-sided alpha of 0.05. RESULTS: Eighty-five patients were randomized and underwent flexible cystoscopy. Three participants were ineligible, one required secondary procedures, and two did not complete the questionnaires. Among the 82 eligible patients, 45 were randomized to standard cystoscopy (arm A) and 37 to the modified cystoscopy (arm B) with mean pain scores of 23.20 and 11.97, respectively (P = .039). Mean anxiety scores were 2.09 and 0.88 for arm A and B, respectively (P = .013). CONCLUSION: This study demonstrated a clinically meaningful decrease in pain and anxiety for patients undergoing flexible cystoscopy when employing the modified cystoscopy technique versus the standard practice. This free and straightforward method to improve patient comfort and decrease stress during first time flexible cystoscopy should be considered by clinicians.

A severe complication of intravesical bacillus Calmette-Guerin: An effect of different strains.

The use of intravesical BCG has improved the survival and outcomes in the treatment of bladder cancer. However, the worldwide shortage of OncoTice BCG has caused disruption and changes in treatment regimes, leading to use of alternative strains. We describe a severe complication as the result of using intravesical SII Onco BCG for the treatment bladder cancer, in an 82 year old man presenting with granulomatous epididymo-orchitis.

Longitudinal experience with Studer neobladders: Outcomes and complications.

INTRODUCTION: This study aims to assess the longer-term functional, anatomical, and metabolic outcomes of patients who underwent Studer neobladder (SNB) urinary diversion. METHODS: A retrospective review of patients who underwent SNB at a single center from 1995-2017 (n=116) was performed. Demographics, comorbidities, pathological data, and longer-term functional, anatomical, and metabolic outcomes were collected from hospital records. The primary outcome was voiding function of patients at most recent followup. Secondary outcomes included postoperative complications, renal function, nephrolithiasis, infections, and metabolic outcomes. RESULTS: Excluding those with incomplete followup data, 72 patients with a minimum followup of one year were included for analysis. Median followup was 70±11 months, with 52.8% of patients having ≥5 years of followup. Clean intermittent catheterization (CIC) was used by 22.2% of patient at most recent followup, which was mostly necessitated by bladder overdistension, deteriorating renal function, or recurrent urosepsis despite timed voiding. Patients experienced more daytime and nighttime urinary incontinence in the early postoperative setting, which improved over time. Generally, renal function declined over time; poorer long-term renal function was predicted by hydronephrosis within one year (p=0.002). CONCLUSIONS: Longer-term followup of SNB reveals significant but manageable complications. Gradual decline in renal function was common. Strict adherence to bladder emptying protocols (e.g., timed voiding or CIC) may reduce incidence of renal deterioration, metabolic disorders, and urinary dysfunction. Early onset (<1 year) of hydronephrosis may indicate a need for intervention to preserve long-term renal function.

Prostatic dystrophic calcification following salvage cryotherapy for prostate cancer - an under-reported entity?

BACKGROUND: Salvage cryoablation (SCA) is an accepted treatment for radio-recurrent prostate cancer with well-established oncological and functional outcomes. Based on one of the longest reported prospective follow-ups in the literature (median 12 years) on 187 patients, this study reports what appears to be an under-appreciated finding in eight patients with dystrophic calcifications (DC) of the prostate following SCA, causing severe bladder outlet obstruction. MATERIALS AND METHODS: Between 1995 and 2004, 187 patients underwent SCA, with a median follow-up of 12 years. This database was reviewed for functional and oncological outcomes and DC were evaluated. RESULTS: Functional data was available in 85 patients, amongst whom eight patients were found to develop DC (9.4%) proven when the patients presented with urinary difficulties and attempted transurethral resection was undertaken for bladder outlet obstruction. Mean time for emergence of significant symptoms of bladder outlet obstruction was 8.6 years from SCA (standard deviation (SD) = 6 years). All eightpatients required permanent drainage (seven suprapubic catheters, one nephrostomy). All patients with DC experienced biochemical recurrence (BCR), compared to 57.1% of the patients with no DC (p = 0.01). CONCLUSION: DC following SCA appears to be an under-reported late adverse effect which may only become evident with long follow-up, and should be included in preoperative counselling.

Magnetic resonance imaging-guided transurethral ultrasound ablation in patients with localised prostate cancer: 3-year outcomes of a prospective Phase I study.

OBJECTIVES: To report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. PATIENTS AND METHODS: As a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3 years. RESULTS: A 3-year follow-up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1-0.4) ng/mL, stable to 0.8 (0.4-1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. CONCLUSION: With 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

Does adding local salvage ablation therapy provide survival advantage for patients with locally recurrent prostate cancer following radiotherapy? Whole gland salvage ablation post-radiation failure in prostate cancer.

INTRODUCTION: Some men who experience prostate cancer recurrence post-radiotherapy may be candidates for local salvage therapy, avoiding and delaying systemic treatments. Our aim was to assess the impact of clinical outcomes of adding salvage local treatment in prostate cancer patients who have failed radiation therapy. METHODS: Following radiation biochemical failure, salvage transperineal cryotherapy (sCT, n=186), transrectal high intensity focused ultrasound ablation (sHIFU, n=113), or no salvage treatment (NST, identified from the pan-Canadian Prostate Cancer Risk Stratification [ProCaRS] database, n=982) were compared with propensity-score matching. Primary endpoints were cancer-specific survival (CSS) and overall survival (OS). RESULTS: Median followup was 11.6, 25.1, and 14.3 years following NST, sCT, and sHIFU, respectively. Two propensity score-matched analyses were performed: 1) 196 NST vs. 98 sCT; and 2) 177 NST vs. 59 sHIFU. In the first comparison, there were 78 deaths and 49 prostate cancer deaths for NST vs. 80 deaths and 24 prostate cancer deaths for sCT. There were significant benefits in CSS (p<0.001) and OS (p<0.001) favoring sCT. In the second comparison, there were 52 deaths (31 from prostate cancer) for NST vs. 18 deaths (nine from prostate cancer) for sHIFU. There were no significant differences in CSS or OS possibility attributed to reduced sample size and shorter followup of sHIFU cohort. CONCLUSIONS: In select men with recurrent prostate cancer post-radiation, further local treatment may lead to benefits in CSS. These hypothesis-generating findings should ideally be validated in a prospective clinical trial setting.

Long-term outcomes of two ablation techniques for treatment of radio-recurrent prostate cancer.

BACKGROUND: In men with recurrence of prostate cancer post radiation therapy, further treatment remains a challenge. The default salvage option of androgen-deprivation therapy (ADT) has adverse effects. Alternatively, selected men may be offered salvage therapy to the prostate. Herein, we present long-term oncological outcomes of two whole-gland ablation techniques, cryotherapy (sCT) and high-intensity-focused ultrasound (sHIFU). METHODS: Men undergoing sCT (1995-2004) and sHIFU (2006-2018) at Western University were identified. Oncological endpoints included biochemical recurrence (BCR), ADT initiation, metastases, castration resistance (CRPC), and prostate cancer-specific mortality (PCSM). Survival analysis with competing risks of mortality was performed. Multivariable analysis was performed using Fine and Gray regression. RESULTS: A total of 187 men underwent sCT and 113 sHIFU. Mean (SD) age of the entire cohort was 69.9 (5.9 years), median pre-radiation PSA 9.6 ng/ml (IQR 6.1-15.2), and pre-salvage PSA 4.5 ng/ml (IQR 2.8-7.0). Median total follow-up was 116 months (IQR 67.5-173.8). A total of 170 (57.6%) developed BCR, 68 (23.4%) metastases, 143 (49.3%) were started on ADT, 58 (20.1%) developed CRPC, and 162 (56%) patients died of which 59 (36.4%) were of prostate cancer. On multivariable analysis, sHIFU (HR 1.65, 95% CI 1.15-2.36, p = 0.006) and pre-salvage PSA (HR 1.09, 95% CI 1.06-1.13, p < 0.0001) were associated with a higher risk of BCR. Similarly, sHIFU patients had a higher risk of CRPC (HR 2.31, 95% CI 1.23-4.35, p = 0.009). The cumulative incidence (for both treatments) of PCSM was 16.5% (95% CI 12.2-21.4%) at 10 years and 28.4% (95% CI 22.1-34.9%) at 20 years, with no difference between treatment modalities. Pre-salvage PSA was a common predictor for the measured oncological outcomes. CONCLUSIONS: Although sHIFU had higher BCR and CRPC rates, there were no differences in PCSM when compared with sCT. The long-term oncological data on two ablation techniques highlighted that only 50% of patients started ADT after 10-year follow-up.

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

Anatomical characterization of the inguinal lymph nodes using microcomputed tomography to inform radical inguinal lymph node dissections in penile cancer.

BACKGROUND & OBJECTIVES: Radical inguinal lymph node dissections (rILND) for penile cancer risk significant postoperative lymphocele and lymphedema. However, reducing the risk of lymphatic complications is limited by our understanding of lymphatic anatomy. Therefore, this study aims to elucidate the lymphatic anatomy within the current surgical borders of a rILND. METHODS: To visualize the position of the lymph nodes, tissue packets excised from the inguinal region of five fresh, male cadavers were imaged using microcomputed tomography (µCT). To standardize the position, rotation and size between specimens, each lymph node packet was aligned using a Generalized Procrustes analysis. RESULTS: There was a median of 13.5 lymph nodes (range = 8-18) per packet, with the majority (99%) clustered within a 6 cm radius of the saphenofemoral junction; a region 39%-41% smaller than current surgical borders. No difference existed between the number of nodes between sides, or distribution around the saphenofemoral junction. CONCLUSIONS: This study provides the first 3D, in situ, standardized characterization of lymph node anatomy in the inguinal region using µCT. By using knowledge of the normal lymphatic anatomy, this study can help inform the reduction in borders of rILND to limit disruption and ensure a complete lymphadenectomy.

The history of cryosurgery in Canada: A tale of two cities.

Although not commonly available in Canada, cryosurgery (cryoablation) for prostate cancer has been practiced in many countries. The field of cryoablation has evolved significantly over the past 30 years. Two prostate cryoablation programs were started in Canada in the early 1990s, in London, ON and Calgary, AB, focusing, respectively, on salvage therapy following radiation failure and primary local treatment. This article chronicles the development of the two programs and outlines the scientific and clinical contributions by investigators at the two centers.

Cryosurgery Versus Primary Androgen Deprivation Therapy for Locally Recurrent Prostate Cancer After Primary Radiotherapy: A Propensity-Matched Survival Analysis.

Background Optimal management of isolated local recurrence of prostate cancer after primary radiotherapy remains to be defined. Up-front androgen deprivation therapy (ADT) is widely used but may adversely affect the quality of life and is essentially a palliative treatment. Local salvage carries a different side-effect profile and is potentially curative, but it has not been compared to ADT. Materials and methods We conducted a propensity-matched analysis of cohorts of men treated with either whole gland cryotherapy (CRYO) or primary ADT following the diagnosis of locally recurrent prostate cancer. Our specific objectives were to compare overall survival (OS) and prostate cancer-specific mortality (PCSM) between CRYO vs. ADT. Results After a one-to-one matching, 169 patients from each cohort were included in comparisons. Median follow-up time was 6.7 years (ADT) vs. 18 years (CRYO). The 10-year PCSM was 18.5% (ADT) vs. 16.2% (CRYO), which was not statistically different [hazard ratioo (HR): 0.69, 95% CI: 0.36-1.34, p=0.27]. The median OS was 12.3 years (CRYO) versus 10.2 years (ADT) (HR: 0.63, 95% CI: 0.42-0.95, p=0.03). Conclusions While PCSM was similar between the two strategies, CRYO was associated with a longer OS compared to primary ADT. Given the retrospective nature of the trial, these results should be considered hypothesis-generating, and phase III trials comparing these two options are required to further explore these findings.

Salvage open radical prostatectomy for recurrent prostate cancer following MRI-guided transurethral ultrasound ablation (TULSA) of the prostate: feasibility and efficacy.

Introduction: MRI-guided transurethral ultrasound ablation (TULSA) is a novel modality for minimally invasive ablation in patients with localised prostate cancer (PCa). A multi-national Phase 1 (30 patients) and subsequent Phase 2 (115 patients) study showed TULSA to be feasible, safe and well tolerated. However, technical viability and safety of salvage prostatectomy for those who failed TULSA is unclear. Herein, we report the feasibility and morbidity of salvage radical prostatectomy (sRP) post-TULSA.Methods: Four patients with biopsy-proven residual cancer following TULSA underwent open retropubic sRP within 39 months of TULSA. Peri-and post-operative morbidity were reported. Detailed histopathologic assessment is reported.Results: Median follow-up was 43 months after sRP. Mean operating times, blood loss, and length of stay were 210 min, 866 ml, and 3.5 days, respectively. Intraoperative finding of some fibrotic reaction of endopelvic and Denonvilliers fascia was characteristic. There were no perioperative complications. Whole-mount pathology sections showed one pT2b and three pT3a, suggesting under-staging pre-TULSA. Location of disease was compatible with persistent cancer mostly in the untreated peripheral safety region. One man received an artificial urinary sphincter. All men experienced erectile dysfunction responsive to treatment. Two patients with positive surgical margins had PSA progression requiring salvage radiation, with one requiring long-term androgen deprivation therapy.Conclusions: RP is a viable and safe salvage option if TULSA fails. Technical difficulty and perioperative morbidity were negligible and attributable to minimal peri-prostatic reaction from TULSA.

A Comparison of Guided Video Reflection versus Self-Regulated Learning to Teach Knot Tying to Medical Students: A Pilot Randomized Controlled Trial.

OBJECTIVES: Self-regulated learning has been proposed as a resource saving alternative for learning knot tying. However, this may be hindered by the Dunning-Kruger effect. A potential alternative is guided video reflection. The objectives of this study are to compare the performance and self-assessment abilities amongst medical students learning knot tying using either a traditional self-regulated approach versus guided video reflection. DESIGN: This randomized, single-blinded, controlled trial used a pre-post-retention test design. All knot tying performances were video recorded and assessed nonsequentially by blinded evaluators using a modified Objective Structured Assessment of Technical Skills tool. PARTICIPANTS: This study recruited 31 first- and second-year medical students and 6 senior urology residents from Western University in Canada. RESULTS: At baseline, the performances of the experts were significantly higher than the experimental groups (F3,85 = 9.080, p < 0.001). After the intervention, there was a significant increase in the performance for both experimental groups compared to the pretest period (p < 0.001). The scores between the experimental groups were not significantly different (p = 0.338). The improved performances of both groups were sustained on retention testing (p < 0.001). The self-assessment abilities were accurate for both experimental groups at baseline. However, at the post-test period the accuracy was poor (interclass correlation 0.361) for the self-regulated group, while remaining moderately (interclass correlation 0.685) accurate for the reflection group. CONCLUSIONS: Students using guided video reflection were able to achieve competency and maintained their knot tying skills to the same degree as those who used the self-regulated approach. These results may be due to the positive effects of reflection on self-assessment abilities and subsequent improvement in goal setting for further practice.

Spontaneous distal ureteric rupture: A rare case report and review of literature.

Spontaneous rupture of the ureter is a very interesting and unusual phenomenon which normally occurs due to ureteral obstruction. We present a case of spontaneous rupture of the distal ureter, secondary to a ureteric calculus. Our patient presented with a history of acute on chronic abdominal pain and was septic on arrival to hospital.

Long-term Testis Cancer Survivors in Canada-Mortality Risks in a Large Population-based Cohort.

BACKGROUND: Testis cancer (TC) patients are young with excellent cancer prognosis. Hence, the risk of late-onset treatment-related morbidity and mortality is of concern due to longer survival after treatment. OBJECTIVE: We set to characterize long-term survival of TC patients through a Canadian population dataset. DESIGN SETTING AND PARTICIPANTS: We used a population-based dataset, the Canadian Census Health and Environment Cohort (CanCHEC), to identify individuals diagnosed with TC between 1991 and 2010. We compared them with all other male individuals without TC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was mortality due to cardiovascular disease (CVD) or nontesticular malignancy. Mann-Whitney or chi-square test was used where applicable. Data were analyzed using a Cox proportional hazard model with and without matching. RESULTS AND LIMITATIONS: We identified 1950 individuals with TC. We compared them with 1 300 295 men with no TC. There were 335 deaths in the study group during the study period (17.2%) with a mean follow-up of 19.6 yr. TC patients were at increased risk of death from secondary malignancies (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.39-1.91; p < 0.0001) with specific risks for hematologic neoplasms (HR 3.86, 95% CI 2.78-5.37; p < 0.001) and other malignancies (HR 2.41, 95% CI 1.76-3.29; p < 0.001). Gastrointestinal, hematologic, and respiratory toxicities were the most common secondary malignancies leading to death. When stratified according to histology, nonseminoma (NS) patients were at significantly increased risk of death from CVD (HR 2.03, 95% CI 1.27-3.25; p = 0.0032). Individuals with seminoma were at increased risk of death from other nontestis neoplasms (HR 1.46, 95% CI 1.17-1.82; p = 0.0007), specifically hematologic neoplasms (HR 2.09, 95% CI 1.18-3.72; p = 0.0118). CONCLUSIONS: NS patients are at increased risk of CVD-related death, whereas seminoma patients are at increased risk of death from non-testis-related malignancies. PATIENT SUMMARY: We report long-term mortality following diagnosis of testis cancer. Nonseminoma patients have an increased risk of death from cardiovascular disease, while seminoma patients have an increased risk of death from secondary malignancies.