Adverse health outcomes and global quality of life in long-term testicular cancer survivors: a longitudinal 30-year perspective.

BACKGROUND: The aim of this study was to characterize the prevalence of self-reported adverse health outcomes (AHOs), track changes in AHOs, and examine their impact on health-related quality of life (HrQoL) in testicular cancer survivors (TCSs) who were diagnosed between 1980 and 1994. These assessments were conducted during two survey waves (SWs), with the first occurring ∼12 years after surgery-only or platinum-based chemotherapy (PBCT), and the second ∼28 years after initial treatment. The study primarily focused on 'typical AHOs', which included Peripheral Sensory Neuropathy (PSN), Raynaud's phenomenon, Tinnitus, and Hearing loss. PATIENTS AND METHODS: A total of 427 TCSs were included in the evaluation, distributed as follows: surgery-only group (n = 155), PBCT-standard group with ≤850 mg cisplatin (n = 222), and PBCT-high group with >850 mg cisplatin (n = 50). For comparison of HrQoL, men from the general population served as a control group (referred to as 'Norms'). The statistical significance level was set at P < 0.05, and clinical importance, in terms of testing HrQoL differences, was defined as Δ ≥2.5 points. RESULTS: A higher number of TCSs who underwent PBCT reported experiencing typical AHOs compared with those who had surgery only. The highest prevalence rates were observed among TCSs who had undergone PBCT-high. Further, the number of TCSs describing typical AHOs, except Raynaud's phenomenon, increased during the observation period of 16 years. At the last SW, a median of 4 AHOs (any type) were reported after PBCT-high compared with a median of 2 AHOs after Surgery-only or after PBCT-standard. With Surgery-only as reference, PBCT-high, but not PBCT-standard, was associated with decreasing physical HrQoL in the last SW (A2 Regression coefficient: -4.3; P = 0.008). When comparing all TCSs with Norms no clinically important difference in physical and mental HrQoL was observed at either SW. However, at the last SW, TCSs after PBCT-high therapy represented a subgroup of TCSs with clinically important impairment of HRQoL. Of the typical AHOs, only PSN reduced HrQoL. Chronic fatigue, pain, anxiety/depression, sexual dysfunction, unemployment, being single, and low education were additional covariates. CONCLUSIONS: After a median of 28 years since their treatment, HrQoL in TCSs was found to be comparable to that of Norms. This similarity held true even though AHOs, especially after PBCT-high, were becoming more prevalent among TCSs. The study revealed that individuals with a history of PBCT-high are at a high risk of experiencing a significantly increased prevalence of long-term AHOs, which subsequently leads to diminished HrQoL. It is crucial to recognize and provide specialized attention to these TCSs during lifelong follow-up care.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA).

BACKGROUND: The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter >4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. PATIENTS AND METHODS: From 2007 to 2010, 897 patients were included in a prospective, population-based, risk-adapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (n = 469) or surveillance (n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. RESULTS: At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, P = 0.011] and tumor diameter >4 cm (HR 2.7, P < 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin <7 × AUC compared with that in patients receiving ≥7 × AUC. CONCLUSION: Stromal invasion in the rete testis and tumor diameter >4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.

Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

BACKGROUND: Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. PATIENTS AND METHODS: Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. RESULTS: Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. CONCLUSIONS: The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important.

Personalizing, not patronizing: the case for patient autonomy by unbiased presentation of management options in stage I testicular cancer.

Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is ∼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all.

One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group.

BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. PATIENTS AND METHODS: In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. CONCLUSIONS: The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.

C-reactive protein; a potential marker of second cancer and cardiovascular disease in testicular cancer survivors?

INTRODUCTION: C-reactive protein (CRP) is a marker of cardiovascular disease (CVD). There is conflicting evidence regarding CRP as a marker of future cancer. We studied whether CRP predicts CVD and consecutive cancer in testicular cancer survivors (TCSs). PATIENTS AND METHODS: During 1998-2001, 586 TCSs with a high sensitivity CRP ≤ 10 mg/L were identified median 11 (4-21) years after treatment (FU-1). A second follow-up survey (FU-2) was conducted median 8 (6-9) years after FU-1. At FU-2 we obtained information about post-FU-1 CVD (cardiovascular death, nonfatal myocardial infarction, stroke, revascularisation or heart failure). Information about post-FU-1 non-germ cell cancer and cardiovascular death in all patients were retrieved from the Cancer Registry of Norway. RESULTS: After FU-1 31 (5.3%) of 586 patients developed non-germ cell cancer (excluding localised prostate cancer), while 28 (4.9%) developed CVD. Cox regression analyses showed that patients with CRP ≥1.5mg/L had 2.21 (95% CI 1.04-4.70) times higher risk of developing non-germ cell cancer and 2.79 (95% CI 1.22-6.34) times higher risk for CVD compared to patients with CRP <1.5mg/L at FU-1. CONCLUSION: In long-term TCSs, CRP may serve as a potential marker of cardiovascular events and a second cancer.

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors.

INTRODUCTION: We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of >or=5% for developing a fatal cardiovascular event qualify for high-risk status. METHODS: One thousand one hundred thirty-four TC survivors treated 1980-1994 participated in this study (1998-2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose 850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE >or=5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group. RESULTS: Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3-8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis. CONCLUSION: The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.

Components of the metabolic syndrome in long-term survivors of testicular cancer.

BACKGROUND: A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC treatment is examined in long-term survivors. PATIENTS AND METHODS: In a national follow-up study (1998-2002), 1463 TC survivors (diagnosed 1980-1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) 850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition. RESULTS: Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-4.7]. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3-3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status. CONCLUSION: TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.