Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours.

OBJECTIVES: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. PATIENTS AND METHODS: Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. RESULTS: Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. CONCLUSIONS: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.

Risk and mortality of testicular cancer in patients with neurodevelopmental or other psychiatric disorders.

BACKGROUND: Both testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT. METHOD: This is a nested case-control study including 6166 TGCT patients diagnosed during 1992-2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death. RESULTS: History of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09-2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death. CONCLUSIONS: We report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders.

Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients.

OBJECTIVE: To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. MATERIALS AND METHODS: Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alpha-fetoprotein; ß-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and post-chemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out ), was analysed using decision curve analysis. RESULTS: Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. CONCLUSIONS: The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.

Prevalence and predictors for fertility-related distress among 1010 young adults 1.5 years following cancer diagnosis - results from the population-based Fex-Can Cohort study.

BACKGROUND: Cancer treatment during reproductive ages may negatively impact fertility and there is a need of firm knowledge about the prevalence and predictors of fertility-related distress. The aim was to examine fertility-related distress in a population-based sample of young women and men recently treated for cancer and to identify predictors for this outcome. MATERIAL AND METHODS: This nationwide cohort study included 1010 individuals (694 women and 316 men), mean age 34.5 ± 4.9 and 32.1 ± 5.5, respectively, diagnosed with breast, cervical, ovarian, testicular cancers, brain tumors or lymphoma at ages 18-39 in Sweden. Participants completed a survey 1.5-year post-diagnosis to assess fertility-related distress (RCAC), emotional distress (HADS) and self-efficacy, as well as sociodemographic and clinical factors and fertility preservation. Logistic regression was used to examine associations between explanatory factors and high fertility-related distress (RCAC subscale mean >4). RESULTS: Many participants (69% of women and 47% of men) had previous children and about half reported a wish for future children. High fertility-related distress was more prevalent among women (54%) than men (27%), and women were more likely than men to report distress concerning all but one RCAC dimension after adjustment for sociodemographic factors. Use of fertility preservation was unevenly distributed (15% of women and 71% of men) and was not associated with decreased fertility-related distress. In multivariable logistic regression models, a wish for future children, being single, not having previous children, symptoms of anxiety and low self-efficacy regarding one's ability to handle threats of infertility were associated with high fertility-related distress. CONCLUSION: This nationwide study found a high prevalence of fertility-related distress in young women and men recently treated for cancer and identified sociodemographic and psychological predictors. Fertility preservation was not found to act as a buffer against fertility-related distress, indicating the continuous need to identify strategies to alleviate fertility distress following cancer.

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial.

BACKGROUND: Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. METHODS: In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0-2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. FINDINGS: Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6-13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7-46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. INTERPRETATION: Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations. FUNDING: Janssen Research & Development.

Low-grade inflammation in survivors of childhood cancer and testicular cancer and its association with hypogonadism and metabolic risk factors.

BACKGROUND: In childhood (CCS) and testicular cancer (TCS) survivors, low-grade inflammation may represent a link between testosterone deficiency (hypogonadism) and risk of metabolic syndrome. We aimed to study levels of inflammatory markers in CCS and TCS and the association with hypogonadism and future cardio-metabolic risk factors. METHODS: Serum levels of inflammatory markers and testosterone were analyzed in CCS (n = 90), and TCS (n = 64, median time from diagnosis: 20 and 2.0 years, respectively), and in controls (n = 44). Differences in levels between patients and controls were calculated using univariate analysis of variance. T-test and logistic regression were applied to compare levels of cardio-metabolic risk factors and odds ratio (OR) of hypogonadism and metabolic syndrome in low and high inflammatory marker groups after 4-12 years of follow up. Adjustment for age, smoking, and active cancer was made. RESULTS: TCS and CCS, as compared to controls, had 1.44 (95%CI 1.06-1.96) and 1.25 (95 CI 1.02-1.53) times higher levels of IL-8, respectively. High IL-6 levels were associated with hypogonadism at baseline (OR 2.83, 95%CI 1.25-6.43) and the association was stronger for high IL-6 combined with low IL-10 levels (OR 3.10, 95%CI 1.37-7.01). High IL-6 levels were also associated with higher BMI, waist circumference, insulin, and HbA1c at follow up. High TNF-α was associated with higher diastolic blood pressure. No individual inflammatory marker was significantly associated with risk of metabolic syndrome at follow up. High IL-6 combined with low IL-10 levels were associated with risk of metabolic syndrome (OR 3.83, 95%CI 1.07-13.75), however not statistically significantly after adjustment. CONCLUSION: TCS and CCS present with low-grade inflammation. High IL-6 levels were associated with hypogonadism and cardio-metabolic risk factors. Low IL-10 levels might reinforce the IL-6 mediated risk of developing metabolic syndrome.

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Fertility-related information received by young women and men with cancer - a population-based survey.

BACKGROUND: Infertility is a well-known sequela of cancer treatment. Despite guidelines recommending early discussions about risk of fertility impairment and fertility preservation options, not all patients of reproductive age receive such information. AIMS: This study aimed to investigate young adult cancer patients' receipt of fertility-related information and use of fertility preservation, and to identify sociodemographic and clinical factors associated with receipt of information. MATERIALS AND METHODS: A population-based cross-sectional survey study was conducted with 1010 young adults with cancer in Sweden (response rate 67%). The inclusion criteria were: a previous diagnosis of breast cancer, cervical cancer, ovarian cancer, brain tumor, lymphoma or testicular cancer between 2016 and 2017, at an age between 18 and 39 years. Data were analyzed using logistic regression models. RESULTS: A majority of men (81%) and women (78%) reported having received information about the potential impact of cancer/treatment on their fertility. A higher percentage of men than women reported being informed about fertility preservation (84% men vs. 40% women, p < .001) and using gamete or gonadal cryopreservation (71% men vs. 15% women, p < .001). Patients with brain tumors and patients without a pretreatment desire for children were less likely to report being informed about potential impact on their fertility and about fertility preservation. In addition, being born outside Sweden was negatively associated with reported receipt of information about impact of cancer treatment on fertility. Among women, older age (>35 years), non-heterosexuality and being a parent were additional factors negatively associated with reported receipt of information about fertility preservation. CONCLUSION: There is room for improvement in the equal provision of information about fertility issues to young adult cancer patients.

Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register study.

BACKGROUND: Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. METHODS AND FINDINGS: In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. CONCLUSIONS: No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.

Prematurity and neonatal outcome including congenital malformations after maternal malignancy within six months prior to or during pregnancy.

INTRODUCTION: The proportion of women who postpone childbearing is increasing. As malignancy risk increases with age, pregnancy in connection with malignancy will become more common. MATERIAL AND METHODS: We compared infants born 1994-2011 to women with a malignancy within six months prior to the last menstrual period or during pregnancy with offspring of women without a previous malignancy. Five national registers were used. RESULTS: A total of 790 women with a malignancy diagnosis from six months prior to the last menstrual period up to delivery were identified. Their 802 infants were compared with 1 742 757 infants of women without a malignancy. A high rate of prematurity was found, especially when the malignancy was diagnosed during the second or third trimesters (33%). Most of these premature births were the result of induced delivery before 35 weeks (91%). The most remarkable finding is the observation that these premature infants had a significantly higher risk for neonatal morbidity than premature infants in the control group with an adjusted odds ratio of 2.67 (95% confidence interval; 1.86-3.84). We found a significantly increased risk of mainly relatively mild malformations among infants of women with a malignancy diagnosis within six months prior to the last menstrual period or during the first trimester with a risk ratio of 1.81 (95% confidence interval; 1.20-2.61). CONCLUSIONS: A high incidence of prematurity, mostly due to induced delivery, was found, including an increased risk for neonatal morbidity among these infants. An increased risk for relatively mild malformations was also found.

Characteristics of the Offspring of Women with a History of Malignancy, Excluding Congenital Malformations.

OBJECTIVE: To study the characteristics (except congenital malformations) of offspring born to women with a history of malignancy. METHODS: Data were obtained by linkage between four different Swedish national health registers. We compared the offspring born between 1994 and 2011 of women with a history of malignancy with all other infants. Survival of the infants was followed up through 2013. Adjusting for confounders was performed using Mantel-Haenszel methodology. We identified 7315 infants born to women with a history of a malignancy diagnosed at least 1 year before delivery. The total number of deliveries in Sweden in these years was 1 746 870, with 1 780 112 infants being born. We assessed rates of intrauterine death, preterm birth, low birth weight, and the nature of intrauterine growth. We also examined neonatal diagnoses (asphyxia, chronic respiratory condition, intracranial hemorrhage, jaundice, hypoglycemia, CNS symptoms) and infant death. RESULTS: In women with a history of malignancy, we found no significantly increased risk for stillbirth or infant death. There were elevated rates of preterm birth (OR 1.50, 95% CI 1.37 to 1.64), very preterm birth (OR 1.89, 95% CI 1.54 to 2.32), and low birth weight (OR 1.50, 95% CI 1.34 to 1.68). There was a significantly increased risk of birth asphyxia, jaundice, hypoglycemia, and low Apgar score among infants born to women with a history of malignancy (OR 1.24, 95% CI 1.15 to 1.33), and this risk was maintained after excluding infants born after IVF. CONCLUSION: We found an increased risk of preterm birth and low birth weight among infants of women with a history of malignancy, and as a result, found an increased risk of neonatal morbidity. No significant increase in risk of intrauterine or postnatal death was noted.

Bilateral testicular germ cell tumors in patients treated for clinical stage I non-seminoma within two risk-adapted SWENOTECA protocols.

BACKGROUND: A contralateral tumor occurs in 3.5-5% of men diagnosed with testicular germ cell cancer (TGCC). Biopsy of the contralateral testis may detect intratubular germ cell neoplasia ITGCNU, a precursor of TGCC. Biopsy of the contralateral testis to detect ITGCNU is controversial. If adjuvant chemotherapy (ACT) protects against bilateral cancer is debated. MATERIAL AND METHODS: A total of 1003 patients with clinical stage I (CS I) non-seminomatous testicular germ cell cancer (NSGCT) were included in two prospective, population-based protocols. Fifteen patients were excluded. Treatment was either adjuvant chemotherapy (n = 494), or surveillance (n = 494). Contralateral testicular biopsy was recommended for all patients, but was performed only in 282 patients. In case of ITGCNU radiotherapy (RT) to 16 Gy was recommended. RESULTS: During a follow-up of 8.3 years, 31 (3.6%) patients developed contralateral TGCC. ITGCNU was detected in 3.2% (9/282) of biopsied patients. The incidence of bilateral TGCC was similar following ACT, 2.5% (11/494), and surveillance, 3.4% (13/494), p = 0.41. Young age was a risk factor for metachronous TGCC (HR 0.93; 95% CI 0.88-0.99, p = 0.02). In total 2.2% (6/273) of patients without ITGCNU in the biopsy developed contralateral TGCC. One irradiated patient developed contralateral cancer, and one developed contralateral tumor before RT was given. CONCLUSION: ACT did not reduce the incidence of contralateral TGCC. Young patients had the highest risk of developing contralateral TGCC. The proportion of false negatives biopsies was higher than reported in earlier trials, but this may in part be related to patient selection, single biopsies and lack of mandatory immunohistochemistry.

[Drastic changes in the treatment of metastatic prostate cancer]. / Behandling av metastaserad prostatacancer.

The treatment of metastatic prostate  cancer has seen drastic changes in the recent years with more intense treatment at initial diagnose. The new standard is combination therapy with castration as the backbone and the addition of new hormonal therapies with or without chemotherapy. For patients with minimal metastatic spread it is also recommended to give radiotherapy to the primary tumour. Since many patients now can look forward to longer survival it is paramount to take care of the side-effects of the treatments, where focus is on cardiovascular disease and bone health management. Precision medicine has started also in prostate cancer; testing of BRCA1/2 mutation is mandatory for treatment with PARP inhibitors.

Primary Retroperitoneal Lymph Node Dissection as Treatment for Low-volume Metastatic Seminoma in a Population-based Cohort: The Swedish Norwegian Testicular Cancer Group Experience.

Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy. Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS). Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13-24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16-30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4-14). PFS was 90% (95% confidence interval: 0.86-1) and OS was 100% at 24 mo. Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity. Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium.

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

Implementation of the measure of case discussion complexity to guide selection of prostate cancer patients for multidisciplinary team meetings.

BACKGROUND: Multidisciplinary team meetings (MDTMs) provide an integrated team approach to ensure individualized and evidence-based treatment recommendations and best expert advice in cancer care. A growing number of patients and more complex treatment options challenge MDTM resources and evoke needs for case prioritization. In this process, decision aids could provide streamlining and standardize evaluation of case complexity. We applied the recently developed Measure of Case Discussion Complexity, MeDiC, instrument with the aim to validate its performance in another healthcare setting and diagnostic area as a means to provide cases for full MDTM discussions. METHODS: The 26-item MeDiC instrument evaluates case complexity and was applied to 364 men with newly diagnosed prostate cancer in Sweden. MeDiC scores were generated from individual-level health data and were correlated with clinicopathological parameters, healthcare setting, and the observed clinical case selection for MDTMs. RESULTS: Application of the MeDiC instrument was feasible with rapid scoring based on available clinical data. Patients with high-risk prostate cancers had significantly higher MeDiC scores than patients with low or intermediate-risk cancers. In the total study, population affected lymph nodes and metastatic disease significantly influenced MDTM referral, whereas comorbidities and age did not predict MDTM referral. When individual patient MeDiC scores were compared to the clinical MDTM case selection, advanced stage, T3/T4 tumors, involved lymph nodes, presence of metastases and significant physical comorbidity were identified as key MDTM predictive factors. CONCLUSIONS: Application of the MeDiC instrument in prostate cancer may be used to streamline case selection for MDTMs in cancer care and may complement clinical case selection.

Do young adults with cancer receive information about treatment-related impact on sex life? Results from a population-based study.

BACKGROUND: Sexual dysfunction is common following a cancer diagnosis in young adulthood (18-39 years) and problems related to sex life are ranked among the core concerns in this age group. Yet, few studies have investigated to what extent adults younger than 40, receive information from healthcare providers about the potential impact of cancer and its treatment on their sex life. METHODS: A population-based cross-sectional survey study was conducted with 1010 young adults 1.5 years after being diagnosed with cancer (response rate 67%). Patients with breast, cervical, ovarian and testicular cancer, lymphoma, and brain tumors were identified in national quality registries. Sociodemographic and clinical factors associated with receiving information were examined using multivariable binary logistic regression. RESULTS: Men to a higher extent than women reported having received information about potential cancer-related impact on their sex life (68% vs. 54%, p < 0.001). Receipt of information varied across diagnoses; in separate regression models, using lymphoma as reference, both women and men with brain tumors were less likely to receive information (women: OR 0.10, CI = 0.03-0.30; men: OR 0.37, CI = 0.16-0.85). More intensive treatment was associated with higher odds of receiving information in both women (OR 1.89; CI = 1.28-2.79) and men (OR 2.08; CI = 1.09-3.94). None of the sociodemographic factors were associated with receipt of information. CONCLUSIONS: To improve sexual health communication to young adults with cancer, we recommend diagnosis-specific routines that clarify when in the disease trajectory to discuss these issues with patients and what to address in these conversations.

A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and 68Ga-PSMA-PET for biochemical relapse after radical prostatectomy - The PROPER 1 trial.

Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still ≥ 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.Clinical trial registration numbers: NCT02699424&ISRCTN45905321.

Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group.

BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.