Excess weight, weight gain, and prostate cancer risk and prognosis: the PROCA-life study.

BACKGROUND: Studies of excess weight and weight changes throughout adult life for prostate cancer (PCa) risk and prognosis have shown inconsistent results. METHODS: In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), 16,960 healthy men from the prospective cohort Tromsø Study (1994-2016) were included. Body mass index (BMI) and weight were measured at all four attendings, and weight change was calculated as the difference between the first and last of either Tromsø4, Tromsø5 or Tromsø6. Overall, 904 men developed PCa during 16 years of follow-up, and Poisson regression with fractional polynomials was used to investigate trends in incidence. Cox proportional hazard and logistic regression models were used to study associations between measurements of BMI and weight change and PCa risk, severity, and mortality. RESULTS: At study entry, 46% of the participants (median age 44 years) were overweight, and 14% were obese (BMI > 30 kg/m2). We observed a 127% increase in overall age adjusted PCa incidence in the cohort during 1995 through 2019. No overall associations between BMI or weight change and PCa risk were observed. However, in sub-group analysis, weight gain among obese men was associated with a three-fold higher PCa risk (HR 3.03, 95% CI 1.39-6.58) compared with obese men with stable weight. Overweight was associated with lower risk of metastatic cancer (OR 0.48, 95% CI 0.30-0.75) at diagnosis. Men with obesity had higher risk of PCa-specific death (HR 1.72, 95% CI 1.03-2.88), while nonsmoking obese PCa cases had two times higher PCa-specific mortality compared with normal weighted PCa cases (HR 2.10, 95% CI 1.11-3.70). INTERPRETATION: In our cohort, weight gain among obese men was associated with higher risk of PCa, and obesity was associated with higher PCa-specific mortality, especially among nonsmokers. The relationship between weight and risk for PCa remains complicated, and future studies are needed to determine clinical implications.

Association of physical activity with overall mortality among long-term testicular cancer survivors: A longitudinal study.

Physical activity (PA) has been associated with reduced mortality among cancer survivors, but no study has focused on testicular cancer survivors (TCSs). We aimed to investigate the association of PA measured twice during survivorship with overall mortality in TCSs. TCSs treated during 1980 to 1994 participated in a nationwide longitudinal survey between 1998 to 2002 (S1: n = 1392) and 2007 to 2009 (S2: n = 1011). PA was self-reported by asking for the average hours per week of leisure-time PA in the past year. Responses were converted into metabolic equivalent task hours/week (MET-h/wk) and participants were categorized into: Inactives (0 MET-h/wk), Low-Actives (2-6 MET-h/wk), Actives (10-18 MET-h/wk) and High-Actives (20-48 MET-h/wk). Mortality from S1 and S2, respectively, was analyzed using the Kaplan-Meier estimator and Cox proportional hazards models until the End of Study (December 31, 2020). Mean age at S1 was 45 years (SD 10.2). Nineteen percent (n = 268) of TCSs died between S1 and EoS, with 138 dying after S2. Compared to Inactives at S1, the mortality risk among Actives was 51% lower (HR 0.49, 95% CI: 0.29-0.84) with no further mortality reduction among High-Actives. At S2, the mortality risk was at least 60% lower among the Actives, High-Actives and even the Low-Actives compared to the Inactives. Persistent Actives (≥10 MET-h/wk at S1 and S2) had a 51% lower mortality risk compared to Persistent Inactives (<10 MET-h/wk at S1 and S2; HR 0.49, 95% CI: 0.30-0.82). During long-term survivorship after TC treatment, regular and maintained PA were associated with an overall mortality risk reduction of at least 50%.

Patient-reported outcomes after curative treatment for prostate cancer with prostatectomy, primary radiotherapy or salvage radiotherapy.

BACKGROUND: Trials reporting adverse health outcomes (AHOs) in terms of patient-reported outcome measures (PROMs) after contemporary curative treatment of prostate cancer (PC) are hampered by study heterogeneity and lack of new treatment techniques. Particularly, the evidence regarding toxicities after radiotherapy (RT) with the volumetric arc therapy (VMAT) technique is limited, and comparisons between men treated with surgery, primary radiotherapy (PRT) and salvage radiotherapy (SRT) are lacking. The aim of the study was to evaluate change in PROMs 3 months after treatment with robotic-assisted laparoscopic prostatectomy (RALP), PRT and SRT administered with VMAT. MATERIAL AND METHODS: A prospective cohort study of men with PC who received curative treatment at the University Hospital of North Norway between 2012 and 2017 for RALP and between 2016 and 2021 for radiotherapy was conducted. A cohort of 787 men were included; 406 men treated with RALP, 265 received PRT and 116 received SRT. Patients completed the validated PROM instrument EPIC-26 before (pre-treatment) and 3 months after treatment. EPIC-26 domain summary scores (DSSs) were analysed, and changes from pre-treatment to 3 months reported. Changes were deemed clinically relevant if exceeding validated minimally clinically important differences (MCIDs). RESULTS: Men treated with RALP reported clinically relevant declining urinary incontinence DSS (-41.7 (SD 30.7)) and sexual DSS (-46.1 (SD 30.2)). Men who received PRT reported worsened urinary irritative DSS (-5.2 (SD 19.6)), bowel DSS (-8.2 (SD 15.1)) and hormonal DSS (-9.6 (SD 18.2)). Men treated with SRT experienced worsened urinary incontinence DSS (-7.3 (SD 18.2)), urinary irritative DSS (-7.5 (SD 14.0)), bowel DSS (-12.5 (SD 16.1)), sexual DSS (-14.9 (SD 18.9)) and hormonal DSS (-23.8 (SD 20.9)). CONCLUSION: AHOs 3 months after contemporary curative treatment for PC varied according to treatment modality and worsened in all treatment groups, although most in SRT.

Lifestyle among long-term survivors of cancers in young adulthood.

PURPOSE: To investigate lifestyle in a population-based sample of long-term (≥ 5 years since diagnosis) young adult cancer survivors (YACSs), and explore factors associated with not meeting the lifestyle guidelines for physical activity (PA), body mass index (BMI), and smoking. METHODS: YACSs (n = 3558) diagnosed with breast cancer (BC), colorectal cancer (CRC), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or localized malignant melanoma (MM) between the ages of 19 and 39 years and treated between 1985 and 2009 were invited to complete a mailed questionnaire. Survivors of localized MM treated with limited skin surgery served as a reference group for treatment burden. RESULTS: In total, 1488 YACSs responded (42%), and 1056 YACSs were evaluable and included in the present study (74% females, average age at survey 49 years, average 15 years since diagnosis). Forty-four percent did not meet PA guidelines, 50% reported BMI ≥ 25 and 20% smoked, with no statistically significant differences across diagnostic groups. Male gender, education ≤ 13 years, comorbidity, lymphedema, pain, chronic fatigue, and depressive symptoms were associated with not meeting single and/or an increasing number of lifestyle guidelines. CONCLUSION: A large proportion of long-term YACSs do not meet the lifestyle guidelines for PA, BMI, and/or smoking. Non-adherence to guidelines is associated with several late effects and/or comorbidities that should be considered when designing lifestyle interventions for YACSs.

A population-based study of testicular cancer risk among children and young adults from Norway and Utah, USA.

Similar family-based cancer and genealogy data from Norway and Utah allowed comparisons of the incidence of testicular cancer (TC), and exploration of the role of Scandinavian ancestry and family history of TC in TC risk. Our study utilizes data from the Utah Population Database and Norwegian Population Registers. All males born during 1951-2015 were followed for TC until the age of 29 years. A total of 1,974,287 and 832,836 males were born in Norway and Utah, respectively, of whom 2,686 individuals were diagnosed with TC in Norway and 531 in Utah. The incidence per year of TC in Norway (10.6) was twice that observed in Utah (5.1) for males born in the last period (1980-1984). The incidence rates of TC in Utah did not differ according to the presence or absence of Scandinavian ancestry (p = 0.669). Having a brother diagnosed with TC was a strong risk factor for TC among children born in Norway and Utah, with HR = 9.87 (95% CI 5.68-17.16) and 6.02 (95% CI 4.80-7.55), respectively; with even higher HR observed among the subset of children in Utah with Scandinavian ancestry (HR = 12.30, 95% CI 6.78-22.31). A clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah was observed. These differences in TC rates point to the possibility of environmental influence. Family history of TC is a strong risk factor for developing TC in both populations.

Continuing increased risk of second cancer in long-term testicular cancer survivors after treatment in the cisplatin era.

Using complete information on total treatment burden, this population-based study aimed to investigate second cancer (SC) risk in testicular cancer survivors (TCS) treated in the cisplatin era. The Cancer Registry of Norway identified 5,625 1-year TCS diagnosed 1980-2009. Standardized incidence ratios (SIRs) were calculated to evaluate the total and site-specific incidence of SC compared to the general population. Cox regression analyses evaluated the effect of treatment on the risk of SC. After a median observation time of 16.6 years, 572 TCS developed 651 nongerm cell SCs. The SC risk was increased after surgery only (SIR 1.28), with site-specific increased risks of thyroid cancer (SIR 4.95) and melanoma (SIR 1.94). After chemotherapy (CT), we observed 2.0- to 3.7-fold increased risks for cancers of the small intestine, bladder, kidney and lung. There was a 1.6- to 2.1-fold increased risk of SC after ≥2 cycles of cisplatin-based CT. Radiotherapy (RT) was associated with 1.5- to 4.4-fold increased risks for cancers of the stomach, small intestine, liver, pancreas, lung, kidney and bladder. After combined CT and RT, increased risks emerged for hematological malignancies (SIR 3.23). TCS treated in the cisplatin era have an increased risk of developing SC, in particular after treatment with cisplatin-based CT and/or RT.

Thromboembolic events after high-intensity training during cisplatin-based chemotherapy for testicular cancer: Case reports and review of the literature.

The randomized "Testicular cancer and Aerobic and Strength Training trial" (TAST-trial) aimed to evaluate the effect of high-intensity interval training (HIIT) on cardiorespiratory fitness during cisplatin-based chemotherapy (CBCT) for testicular cancer (TC). Here, we report on an unexpected high number of thromboembolic (TE) events among patients randomized to the intervention arm, and on a review of the literature on TE events in TC patients undergoing CBCT. Patients aged 18 to 60 years with a diagnosis of metastatic germ cell TC, planned for 3 to 4 CBCT cycles, were randomized to a 9 to 12 weeks exercise intervention, or to a single lifestyle counseling session. The exercise intervention included two weekly HIIT sessions, each with 2 to 4 intervals of 2 to 4 minutes at 85% to 95% of peak heart rate. The study was prematurely discontinued after inclusion of 19 of the planned 94 patients, with nine patients randomized to the intervention arm and 10 to the control arm. Three patients in the intervention arm developed TE complications; two with pulmonary embolism and one with myocardial infarction. All three patients had clinical stage IIA TC. No TE complications were observed among patients in the control arm. Our observations indicate that high-intensity aerobic training during CBCT might increase the risk of TE events in TC patients, leading to premature closure of the TAST-trial.

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population-based study in Utah and Norway.

BACKGROUND: In this study, we aimed to evaluate incidence rates and family risk of the most common childhood cancers, tumors in the central nervous system (CNS), and leukemia among individuals from Norway and individuals with Scandinavian ancestry living in Utah. METHODS: We used the Utah Population Database and the Norwegian National Population Register linked to Cancer registries to identify cancers in children born between 1966 and 2015 and their first-degree relatives. We calculated incidence rates and hazards ratios. RESULTS: The overall incidence of CNS tumors increased with consecutive birth cohorts similarly in Utah and Norway (both P < 0.001). Incidence rates of leukemia were more stable and similar in both Utah and in Norway with 4.6/100 000 person-years among children (<15 years) born in the last cohort. A family history of CNS tumors was significantly associated with risk of childhood CNS tumors in Utah HR = 3.05 (95% CI 1.80-5.16) and Norway HR = 2.87 (95% CI 2.20-3.74). In Norway, children with a first-degree relative diagnosed with leukemia had high risk of leukemia (HR = 2.39, 95% CI 1.61-3.55). CONCLUSION: Despite geographical distance and assumed large lifestyle differences, two genetically linked pediatric populations show similar incidences of CNS tumors and leukemia in the period 1966-2015. CNS tumors and leukemia aggregated in families in both countries.

Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study.

BACKGROUND: The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults. METHODS: This is a prospective cohort study including 1,974,287 males born 1951-2015, of whom 2686 were diagnosed with TC before the age of 30. RESULTS: A history of TC in male relatives was significantly associated with a diagnosis of TC among children and young adults, including brothers (6.3-fold), sons (4.7-fold), fathers (4.4-fold), paternal uncles (2.0-fold) and maternal uncles (1.9-fold). Individuals with a father diagnosed with a carcinoma or sarcoma showed an elevated risk (1.1-fold and 1.8-fold, respectively). A family history of mesothelioma was positively associated with a risk of TC [(father (2.8-fold), mother (4.6-fold) and maternal uncles and aunt (4.4-fold)]. Elevated risks were also observed when siblings were diagnosed with malignant melanoma (1.4-fold). The risk of TC was also increased when fathers (11.1-fold), paternal (4.9-fold) and maternal uncles and aunts (4.6-fold) were diagnosed with malignant neuroepithelial-tumours. CONCLUSION: We found an increased risk of TC among children and young adults with a family history of TC, carcinoma, mesothelioma, sarcoma, malignant melanoma and malignant neuroepithelial tumours. Hereditary cancer syndromes might underlie some of the associations reported in this study.

Chronic fatigue and associated factors among long-term survivors of cancers in young adulthood.

Background: Chronic fatigue (CF) is scarcely explored among young adult cancer survivors (YACSs), and more knowledge is needed to develop targeted interventions for YACSs with CF. The present study aimed to investigate the prevalence of CF and associated factors in YACSs. Also, the change of fatigue with time was explored. Material and methods: The present cross-sectional study is part of a nation-wide population based survey of Norwegian survivors of cancer in childhood, adolescence, and young adulthood (The NOR-CAYACS study).YACSs diagnosed at the age of 19-39 years with breast cancer stage ≤ III (BC), colorectal cancer (CRC), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia, or non-metastatic malignant melanoma (MM) were included 5-30 years after diagnosis. Survivors of MM treated with limited surgery were included as a reference group. CF was assessed by the Fatigue Questionnaire. Logistic regression analyses were performed to identify factors associated with CF. Results: In total, 1488 survivors completed the questionnaire (a response rate of 42%), of which 1088 were eligible for the present study. Overall, 25% reported CF. CF was significantly more prevalent among survivors of BC (29%) (p < .001), CRC (29%) (p = .001) and NHL (27%) (p = .003) than among survivors of MM (15%). CF was associated with systemic treatment combined with surgery and/or radiotherapy (p = .018), comorbidity (p = .038), pain (p = .002), numbness in hands/feet (p = .046), and depressive symptoms (p < .001) in the multivariable model. Among survivors with CF, 60% reported that they had been tired since cancer treatment, and among these, 65% reported worsening or no change of fatigue with time. Conclusion: One of four YACSs reported CF 15 years from diagnosis (mean). CF was associated with several possibly treatable factors. Health professionals involved in the follow-up of YACSs should have knowledge of CF and approaches to manage it.

Hearing loss before and after cisplatin-based chemotherapy in testicular cancer survivors: a longitudinal study.

BACKGROUND: Hearing loss is a well-known long-term effect after cisplatin-based chemotherapy (CBCT) in testicular cancer survivors (TCS), but longitudinal data are sparse. We evaluate hearing loss and the impact of age in TCS treated with CBCT in this longitudinal study. MATERIAL AND METHODS: Forty-six TCS treated with CBCT 1980-1994 with audiograms (0.25-8 kHz) pre-chemotherapy (PRE) and at a follow-up survey (SURV) after median 10 years were included (cases). Audiograms at SURV from 46 age-matched TCS without CBCT were included as controls. Linear regression was performed to evaluate predictors for change in the hearing threshold level (HTL) from PRE to SURV. Two definitions of a audiogram-defined hearing loss was applied if: (1) mean HTL for both ears exceeded 20 dB at any frequency 0.25-8 kHz (American Speech-Language-Hearing Association (ASHA) definition) and (2) average HTL for the frequencies 0.5, 1, 2 and 4 kHz exceeded 20 dB (WHO-M4 definition). Self-reported hearing impairment (SURV) was assessed by a questionnaire. RESULTS: Age and cisplatin dose was significantly associated with a greater change in HTL for the frequencies 2-8 kHz. For the 8 kHz frequency, each 100 mg increase in cumulative cisplatin dose was associated with a deterioration of 3.6 dB (95% CI 1.8-5.3, p < .001). The prevalence of hearing loss (ASHA) among cases was 33% PRE, 70% at SURV and 65% among controls at SURV (cases vs. controls, p = .66). According to M4, the prevalence of hearing loss among cases was 6.5% PRE, 13% at SURV and 2.2% among controls at SURV (cases vs. controls, p = .049). Twenty-nine percent of cases, and 33% of controls (p = .70) reported hearing impairment at SURV. CONCLUSION: Cisplatin is associated with a hearing loss particularly at higher frequencies. Age appear to be an important factor for hearing loss regardless of treatment. The ASHA definition overestimates the hearing problem.

Imatinib may reduce chemotherapy-induced pneumonitis. A report on four cases from the SWENOTECA.

BACKGROUND: An increasing number of anticancer drugs have been reported to cause pneumonitis. Chemotherapy-induced pneumonitis may cause severe morbidity and event death. As there has been a lack of effective treatment, new treatment strategies are needed. A previous case report has indicated that imatinib may be useful. PATIENT AND METHODS: The SWENOTECA experience of four cases with severe life-threatening chemotherapy-induced pneumonitis treated with imatinib is presented. RESULTS: All four patients responded to treatment with imatinib. CONCLUSIONS: Imatinib appears to be an effective treatment of severe chemotherapy-induced pneumonitis in germ cell cancer patients.

Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors.

BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. RESULTS: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). CONCLUSION: In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.

The Longitudinal Course of Prospectively Recorded Patient-reported Outcomes in Prostate Cancer Patients Treated with Surgery and Salvage Radiotherapy.

Background: Patient-reported outcome measures (PROMs) after prostate cancer (PC) treatment, including both radical prostatectomy (RP) and salvage radiation therapy (SRT), are under-reported. Objective: To investigate PROMs longitudinally from before SRT until 18 mo after SRT for men treated with contemporary treatment modalities. Design setting and participants: This prospective, longitudinal cohort study included 120 men (whole cohort) treated with SRT administered with volumetric modulated arc radiotherapy from 2016 to 2021 at the University Hospital of North Norway. The whole cohort was followed from before SRT until 18 mo after SRT. A subcohort of 48 men was followed from before RP until 18 mo after SRT. Outcome measurements and statistical analysis: PROMs were collected with the Expanded Prostate Cancer Index-26 (EPIC-26), covering symptoms of urinary incontinence, urinary irritative, bowel, sexual, and hormonal domains. The domain scores were inquired before RP, 3 mo after RP, before SRT, at SRT termination, and 3 and 18 mo after SRT. We used linear mixed models with repeated measurements design to assess changes in PROMs throughout the treatment period. Results and limitations: The median age before SRT was 63 yr. For the whole cohort, all five domains worsened at 3 and 18 mo after SRT compared with those before SRT. The estimated mean changes from before SRT to 18 mo after SRT are as follows: urinary incontinence -13.1, urinary irritative function -10.4, bowel -16.8, sexual function -9.1, and hormonal function -20.2 (at clinically important levels for all domains but sexual). For the subcohort, the mean urinary incontinence, bowel, sexual, and hormonal functions were significantly worsened 3 and 18 mo after SRT compared with those before RP at clinically important levels. Conclusions: Men treated for PC report particular increased severity of urinary, bowel, sexual, and hormonal symptoms after SRT compared with baseline status. Patient summary: For men with prostate cancer, the treatment combination of surgery and salvage radiotherapy worsens urinary incontinence and bowel, sexual, and hormonal functions.

High-dose chemotherapy with autologous stem cell support in patients with metastatic non-seminomatous testicular cancer - a report from the Swedish Norwegian Testicular Cancer Group (SWENOTECA).

BACKGROUND: The SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poor response to standard cisplatin-based chemotherapy. A slow tumor marker decline (HCG T(½) > 3 days, AFP T(½) > 7 days) after BEP or BEP plus ifosfamide was regarded as poor response. The aim of this study was to present survival and toxicity data for patients treated with high-dose chemotherapy (HDCT) within the SWENOTECA IV cancer care program. MATERIAL AND METHODS: In total 882 adult men diagnosed with metastatic NSGCT between July 1995 and June 2007 in Sweden and Norway (except one center) were included in SWENOTECA IV and treated accordingly. Among these, 55 men (6.2%) were treated with HDCT according to three different indications in the protocol: A) poor response to standard-dose intensified chemotherapy (BEP plus ifosfamide); B) vital cancer at surgery after intensified chemotherapy; and C) selected relapses after previous chemotherapy. In situation A and C two HDCT cycles and in situation B one HDCT cycle was recommended. Situation A was the reason for HDCT in 36 patients, B in seven and C in 12 patients. The first HDCT cycle consisted of carboplatin 28 × (GFR + 25) mg, cyclofosfamide 6000 mg/m(2) and etoposide 1750 mg/m(2), administered over four days. In cycle two, etoposide was replaced by tiotepa 480 mg/m(2). RESULTS: After a median follow-up of 7.5 years, overall survival was 72%, 100% and 58%, while failure-free survival was 64%, 71% and 42% in situation A, B and C, respectively. Three patients (5.5%) died during HDCT (renal failure or intracerebral hemorrhage). Nephrotoxicity was the most common non-hematological grade 4 toxicity (n = 5, 9%). CONCLUSION: The population-based SWENOTECA strategy, selecting patients who do not respond adequately to primary standard-dose chemotherapy for immediate treatment intensification with HDCT, is feasible and might be advantageous.

Assessment of late urinary, bowel and sexual function after dose escalation from 70 to 76 Gy using image-guided radiotherapy in curative treatment of prostate cancer.

OBJECTIVE: The aim of this study was to evaluate the late urinary, bowel and sexual function among men with localized or locally advanced prostate cancer treated with curative radiotherapy after the introduction of image-guided radiotherapy to 76 Gy using the Swedish BeamCath® technique. MATERIAL AND METHODS: All patients treated with curative radiotherapy during 2003-2006 were invited to participate in this retrospective study. In total, 87% (158/181) participated in the study. The median observation time was 35 months. Comparisons were made between the standard 70 Gy (n = 73) and the 76 Gy (n = 85) treatment groups. Assessments of late urinary, bowel and sexual function were questionnaire based, and included function items in the Expanded Prostate Cancer Index Composite. RESULTS: Most late urinary and bowel symptoms were reported to occur seldom or never in the majority of men, while late sexual toxicity was reported in a large proportion (66%) of men. Seven men (4%) used diapers. Only 25% (n = 40) reported having an erection firm enough for intercourse. None of the reported urinary or sexual function symptoms differed between the treatment groups. Rectal urgency at least once daily was a more frequent symptom in the 70 Gy group than the 76 Gy group (28% vs 9%, p = 0.006). Painful bowel movements were a more common symptom in the 70 Gy group (11% vs 1%, p = 0.01). CONCLUSION: Dose escalation up to 76 Gy using the BeamCath technique was not associated with more late toxicities than the standard 70 Gy dose.

Mortality and Second Cancer Incidence After Treatment for Testicular Cancer: Psychosocial Health and Lifestyle Are Modifiable Prognostic Factors.

PURPOSE: To evaluate whether selected modifiable patient-reported adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) represent prognostic factors of overall mortality, cancer mortality, and first-time non-germ cell second cancer (SecCa) incidence. PATIENTS AND METHODS: In 775 long-term TCSs (diagnosis: 1980-1994) who previously participated in a quality-of-life survey, 20-year mortality and SecCa incidence were compared between the surgery group (n = 272) and TCSs after platinum-based chemotherapy (PBCT; n = 503). A PBCT standard group (total cisplatin: ≤ 630 mg: n = 124) was separated from a PBCT high subgroup (total cisplatin: > 630 mg; n = 379). Univariate and multivariate analyses (Kaplan-Meier; Cox proportional hazard analyses) included age, treatment, and prior major physical comorbidity as nonmodifiable factors, whereas low socioeconomic status, unhealthy lifestyle, probable depression disorder, and neurotoxicity were modifiable AHOs. RESULTS: For all TCSs, the cumulative overall 20-year mortality was 14% (95% CI, 11.8 to 16.8). Rising age, PBCT high, and comorbidity significantly increased the risk of overall mortality rate. Compared with a low-risk group (no AHO; n = 446) and with exception of neurotoxicity, this risk was further significantly enhanced by 80% in TCSs of a medium-risk group (one or two AHOs; n = 278). In men of a high-risk group (three AHOs; n = 47), the probability of overall mortality and of cancer mortality was eight-fold and five-fold increased, respectively. Risk grouping did not influence on SecCa incidence. CONCLUSION: Self-reported unfavorable modifiable AHO concerning lifestyle and psychosocial health are in TCSs independently and significantly associated with increased overall mortality and cancer mortality. Health professionals and the TCSs themselves, particularly those after PBCT high, should continuously be aware of these risk factors attempting maximal reduction of these AHOs and thereby supporting long-term survival.

Systolic and diastolic blood pressure, prostate cancer risk, treatment, and survival. The PROCA-life study.

BACKGROUND: Inflammation has been linked to prostate cancer and hypertension, but it remains equivocal whether elevated blood pressure (BP) influence prostate cancer risk and survival. METHOD: Using Cox regression models, we examined the association between prediagnostic BP and prostate cancer risk among 12,271 men participating in the Prostate Cancer throughout life (PROCA-life) study. Systolic and diastolic BP were measured. A total of 811 men developed prostate cancer, and followed for additional 7.1 years, and we studied the association between prediagnostic BP and overall mortality among patients with prostate cancer. RESULTS: Men (>45 years) with a systolic BP >150 mmHg had a 35% increased risk of prostate cancer compared with men with a normal systolic BP (<130 mmHg) (HR 1.35, 95% CI 1.08-1.69). Among patients with prostate cancer, men with systolic BP >150 mmHg had a 49% increased overall mortality compared with men with a normal systolic BP (HR 1.49, 1.06-2.01). Among patients with prostate cancer treated with curative intent, those with a high diastolic BP (>90 mmHg) had a threefold increase in overall mortality risk (HR 3.01, 95% CI 1.40-6.46) compared with patients with a normal diastolic BP (<80 mmHg). CONCLUSION: Our results support that systolic and diastolic BP are important factors when balancing disease management in patients with prostate cancer.

Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000-2014: A Population-based Cohort Study.

BACKGROUND: Cisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. OBJECTIVE: To evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. DESIGN SETTING AND PARTICIPANTS: In a population-based study, 506 men administered first-line CBCT during 2000-2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. RESULTS AND LIMITATIONS: Overall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01-3.91), central venous access (OR 2.84, 95% CI 1.46-5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12-5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p < 0.001). CONCLUSIONS: We found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding. PATIENT SUMMARY: We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Metachronous Contralateral Testicular Cancer in the Cisplatin Era: A Population-Based Cohort Study.

PURPOSE: It is hypothesized that cisplatin-based chemotherapy (CBCT) reduces the occurrence of metachronous contralateral (second) germ cell testicular cancer (TC). However, studies including treatment details are lacking. The aim of this study was to assess the second TC risk, emphasizing the impact of previous TC treatment. PATIENTS AND METHODS: Based on the Cancer Registry of Norway, 5,620 men were diagnosed with first TC between 1980 and 2009. Treatment data regarding TC were retrieved from medical records. Cumulative incidences of second TC were estimated, and standardized incidence ratios were calculated. The effect of treatment intensity was investigated using Cox proportional hazard regression. RESULTS: Median follow-up was 18.0 years, during which 218 men were diagnosed with a second TC after median 6.2 years. Overall, the 20-year crude cumulative incidence was 4.0% (95% CI, 3.5 to 4.6), with lower incidence after chemotherapy (CT) (3.2%; 95% CI, 2.5 to 4.0) than after surgery only (5.4%; 95% CI, 4.2 to 6.8). The second TC incidence was also lower for those age ≥ 30 years (2.8%; 95% CI, 2.3 to 3.4) at first TC diagnosis than those age < 30 years (6.0%; 95% CI, 5.0 to 7.1). Overall, the second TC risk was 13-fold higher compared with the risk of developing TC in the general male population (standardized incidence ratio, 13.1; 95% CI, 11.5 to 15.0). With surgery only as reference, treatment with CT significantly reduced the second TC risk (hazard ratio [HR], 0.55). For each additional CBCT cycle administered, the second TC risk decreased significantly after three, four, and more than four cycles (HRs, 0.53, 0.41, and 0.21, respectively). CONCLUSION: Age at first TC diagnosis and treatment intensity influenced the second TC risk, with significantly reduced risks after more than two CBCT cycles.