Risk of positive selection bias in longitudinal surveys among cancer survivors: Lessons learnt from the national Norwegian Testicular Cancer Survivor Study.

BACKGROUND: Selection bias due to non- or incomplete compliance is challenging in surveys. Using data from a longitudinal survey in testicular cancer survivors (TCSs), we identify factors predicting incomplete compliance. METHOD: In a questionnaire-based national survey (1998-2016; three waves) 1,813 > 5 year TCSs were invited to report post-treatment adverse health outcomes (AHOs). We separated complete from partial participants (participation in all three waves versus participation only once or twice). At each wave we additionally identified responders and non-responders based on their questionnaire return at the respective wave. Multivariable logistic regression analysis identified associations between AHOs reported at the first wave and partial participation. Survival differences between Responders and Non-Responders were assessed by the Kaplan-Meier estimate and the logrank test. Level of significance: p < 0.05. RESULTS: Of 1813 TCSs 1,346 TCSs (79 %) completed the first wave's questionnaire, and 783 (58 %) became complete and 653 (42 %) partial participants. Poor socio-economics, unhealthy life style, major co-morbidity and chemotherapy-related AHOs reported at the first survey wave were associated with a significant 1.5-1.9 times increased risk for partial participation. At the two last waves non-responders had significantly decreased overall survival compared with responders. CONCLUSION: Our longitudinal study indicates positive selection bias during the 17 years of a longitudinal survey among TCSs, with fewer AHOs among Complete than among Partial Participants. If not sufficiently compensated for by data from external sources and/or statistical methods, attrition bias in longitudinal surveys may limit the external validity of findings related to cancer survivors' self-reported AHOs.

Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial.

BACKGROUND: Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death. METHODS AND MATERIALS: The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC. RESULTS: Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65). CONCLUSIONS: Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.

Second cancers in radically treated Norwegian prostate cancer patients.

Introduction: The aim of this registry-based cohort study was to estimate second cancer (SC) risk following radical prostate cancer (PC) treatment and evaluate if the risk was influenced by radiotherapy. Materials and methods: We collected data from the Cancer Registry of Norway on all patients with PC as first cancer diagnosis, from 1997 to 2014. Standardized incidence ratios (SIRs) for SC were calculated by comparing our cohort to the standard male population. Subdistribution hazard ratios were estimated in treatment groups, using patients treated with radical prostatectomy (RP) as reference. Results: We analyzed 24,592 radically treated PC patients. The median follow-up was 7.75 and 6.25 years in the external beam radiotherapy (EBRT) and RP-groups, respectively. SIR for SC was indifferent from the reference population in 24,592 radically treated patients, higher following EBRT, SIR 1.12 (1.07-1.17), and lower following RP, SIR 0.93 (0.87-0.99). EBRT treated patients had higher rectal and urinary bladder cancer incidences, SIR 1.38 (1.16-1.64) and 1.49 (1.31-1.69), respectively. The EBRT patients and the patients treated with radiation after RP (RT after RP) had 38 and 27% higher risk of any SC. We found higher risk of bladder cancer for all treatment groups as compared to RP patients. Only EBRT treated patients showed higher risk of rectal and lung cancer. Discussion/conclusions: In our study, we found that PC patients treated with EBRT had an increased incidence of SC compared to the general population. Patients treated with EBRT and RT after RP were found to have increased risk of SCs, using RP patients as reference. The risks of rectal and urinary bladder cancer in patients receiving EBRT were higher compared to both the general population and to patients treated with radical prostatectomy. The risk of SC should be taken into account when discussing treatment for patients and designing follow-up.

Does Prophylactic Radiation Therapy to Avoid Gynecomastia in Patients With Prostate Cancer Increase the Risk of Breast Cancer?

PURPOSE: Prostate cancer (PC) patients who undergo antiandrogen monotherapy are offered prophylactic radiation therapy (PRT) to the breast buds to avoid gynecomastia. The aim of the present study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis was influenced by PRT. METHODS AND MATERIALS: From the Norwegian Cancer Registry, we collected data from all patients with PC as their first cancer diagnosis from 1997 to 2014. We registered all RT given to the patients in the same period and the occurrence of BC diagnosed ≥3 months after the PC diagnosis. The histopathologic diagnoses of all BC cases were collected. Subdistribution hazard ratios for the risk of BC in the PRT and non-PRT groups were estimated. A standardized incidence ratio for BC was calculated by comparing our cohort to the standard male population. RESULTS: We analyzed 59,169 patients with PC, of whom 7864 (13.3%) had received PRT. The median follow-up time was 4 years. Of the 12 men with a diagnosis of BC, 3 had received PRT, and 2 of the 3 were phyllodes tumors. The risk of BC was not significantly different statistically for the patients given PRT compared with the non-PRT group (subdistribution hazard ratio 1.62, 95% confidence interval 0.41-5.62, adjusted for age and time of diagnosis). The standardized incidence ratio was 0.996 (95% confidence interval 0.57-1.75). CONCLUSIONS: In this registry-based study, we did not find an increased risk of BC in PC patients who received PRT. The number of BC cases in our study was low, and the risk of secondary BC after PRT seems to be negligible. The incidence of BC could, however, increase with additional follow-up. Also, 2 patients who had received PRT developed a malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

Long-term Relative Survival after Diagnosis of Testicular Germ Cell Tumor.

BACKGROUND: Long-term relative survival (RS) data for testicular germ cell tumor (TGCT) patients are scarce. We aimed to analyze long-term RS among TGCT patients diagnosed in Norway, between 1953 and 2012. METHODS: Data sources were the Cancer Registry of Norway and the Norwegian Cause of Death Registry. TGCT patients diagnosed during 1953 to 2012 were classified by time of diagnosis, histology, age, and disease extent at diagnosis. Estimates for RS were obtained, and a test comparing overall RS was performed. Corresponding data were obtained for men diagnosed with localized malignant melanoma before age 50. RESULTS: A total of 8,736 TGCT patients were included. RS generally continued to decline with increasing follow-up time, particularly beyond 15 to 30 years, unlike in localized malignant melanoma. Although RS was generally higher for seminomas, the continuing decline was more pronounced than for nonseminomas, even when diagnosed with localized disease. TGCT patients diagnosed before 1980 or after age 40 had lower RS. CONCLUSIONS: Although TGCT RS has improved in recent decades, it continues to decline even beyond 30 years of follow-up, regardless of disease extent at diagnosis. The main cause is probably treatment-induced late effects, particularly affecting seminoma patients. The continued use of adjuvant radiotherapy in seminomas until year 2000 is suspected as a culprit. IMPACT: Long-term TGCT survivors should be closely monitored for the development of late comorbidity. The challenge is to reduce negative consequences of previous and current TGCT treatment on RS while maintaining the excellent cure rates. Further research on causes of long-term morbidity and mortality among TGCT survivors is warranted. Cancer Epidemiol Biomarkers Prev; 25(5); 773-9. ©2016 AACR.

Management of seminomatous testicular cancer: a binational prospective population-based study from the Swedish norwegian testicular cancer study group.

PURPOSE: A binational, population-based treatment protocol was established to prospectively treat and follow patients with seminomatous testicular cancer. The aim was to standardize care for all patients with seminoma to further improve the good results expected for this disease. PATIENTS AND METHODS: From 2000 to 2006, a total of 1,384 Norwegian and Swedish patients were included in the study. Treatment in clinical stage 1 (CS1) was surveillance, adjuvant radiotherapy, or adjuvant carboplatin. In metastatic disease, recommended treatment was radiotherapy in CS2A and cisplatin-based chemotherapy in CS2B or higher. RESULTS: At a median follow-up of 5.2 years, 5-year cause-specific survival was 99.6%. In CS1, 14.3% (65 of 512) of patients relapsed following surveillance, 3.9% (seven of 188) after carboplatin, and 0.8% (four of 481) after radiotherapy. We could not identify any factors predicting relapse in CS1 patients who were subjected to surveillance only. In CS2A, 10.9% (three of 29) patients relapsed after radiotherapy compared with no relapses in CS2A/B patients (zero of 73) treated with chemotherapy (P = .011). CONCLUSION: An international, population-based treatment protocol for testicular seminoma is feasible with excellent results. Surveillance remains a good option for CS1 patients. No factors predicted relapse in CS1 patients on surveillance. Despite resulting in a lower rate of relapse than with adjuvant carboplatin, adjuvant radiotherapy has been abandoned in the Swedish and Norwegian Testicular Cancer Project (SWENOTECA) as a recommended treatment option because of concerns of induction of secondary cancers. The higher number of relapses in radiotherapy-treated CS2A patients when compared with chemotherapy-treated CS2A/B patients is of concern. Late toxicity of cisplatin-based chemotherapy versus radiotherapy must be considered in CS2A patients.