miR-371a-3p Predicting Viable Tumor in Patients Undergoing Retroperitoneal Lymph Node Dissection for Metastatic Testicular Cancer: The SWENOTECA-MIR Study.

PURPOSE: The SWENOTECA-MIR prospective multicenter study aims to assess the clinical value of miR-371a-3p as a novel marker in metastatic germ cell tumor patients undergoing retroperitoneal lymph node dissection (RPLND), to predict the presence of viable residual tumor. MATERIALS AND METHODS: A total of 114 patients (86 nonseminomas, 28 seminomas) who underwent surgery for presumed metastatic disease pre chemotherapy (primary RPLND) and post chemotherapy RPLND were included. The expression of miR-371a-3p was evaluated using reverse transcription-digital droplet polymerase chain reaction before and after RPLND. Pre- and postoperative miR-371a-3p levels were statistically compared, and optimism-corrected performance calculations compared with conventional serum tumor markers. Associations were evaluated by logistic regression. Patients who underwent primary RPLND were categorized into seminoma and nonseminoma groups. RESULTS: Among the seminoma patients (n = 24) undergoing primary RPLND, all had normal conventional markers. Six patients received adjuvant treatment before surgery. miR-371a-3p exhibited a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 21% for viable tumor. The levels of miR-371a-3p significantly decreased after surgery. In the nonseminoma group (n = 18) treated with primary RPLND, 22% had elevated conventional markers and 3 had received prior adjuvant treatment. miR-371a-3p showed a sensitivity of 34%, specificity of 88%, positive predictive value of 67%, and negative predictive value of 62% for the primary nonseminoma patients. No association was observed between stage or prior adjuvant treatment and the outcome of the miR test. In the postchemotherapy group (n = 72), the miR-371a-3p sensitivity was 9%, reducing to 0 when excluding patients with seminoma (n = 4). Teratomas and benign histology were essentially negative. CONCLUSIONS: Our study highlights miR-371a-3p as a fairly sensitive and highly specific marker for prechemotherapy seminomas, outperforming conventional markers. However, in prechemotherapy nonseminomas as well as in postchemotherapy patients, we observed low sensitivity and no significant differences in miR-371a-3p levels before and after surgery, suggesting limited utility for miR-371a-3p in this context.

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.

Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

BACKGROUND: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade. STUDY DESIGN: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden. ENDPOINTS: The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa-specific survival, metastasis-free survival, role-functioning scale (EORTC quality of life questionnaire 30-item core), urinary irritative/obstructive scale (26-item Expanded Prostate Cancer Index Composite [EPIC-26]), bowel scale (EPIC-26), intervention-free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality-adjusted life-years (QALYs), and mean total healthcare costs. PATIENTS AND METHODS: A total of 980 men (aged ≥75 years) with non-metastatic, high-risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini-COG© brief cognitive test. Participants identified by G8 as 'fit' or 'frail' will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years. TRIAL REGISTRATION: Ethics approval has been granted in Norway (457593), Denmark (H-22051998), Finland (R23043) and Sweden (Dnr 2023-05296-01). The trial is registered on Clinicaltrials.org (NCT05448547).

¹77Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. / Behandling av kastrasjonsresistent metastatisk prostatakreft med [¹77Lu]PSMA-radioligand.

Background: Treatment of castration-resistant metastatic prostate cancer with [¹77Lu]PSMA radioligand. Case presentation: A man in his seventies with metastatic prostate cancer received castration therapy for four years, developing castration-resistant disease. PET/CT with [68Ga]PSMA-11 showed high uptake in metastatic lymph nodes. The patient received 7.4 GBq [¹77Lu]PSMA-I&T (Curium, Finland) as five treatments at five-week intervals. Five weeks after the first treatment, p-PSA dropped from 154 to 53 µg/L. Five weeks after the fifth treatment, p-PSA was 1.8 µg/L. [68Ga]PSMA-11 PET/CT showed significant reduction in the size of metastases, with the largest decreasing in diameter from 10 to 4 mm. Seven months after the fifth treatment, p-PSA increased to 14.3 µg/L, and [68Ga]PSMA-11 PET/ CT revealed additional skeletal metastases, while the lymph node metastases remained unchanged. Thus, the treatment had a good but temporary effect on the metastases. Interpretation: Treatment with [¹77Lu]PSMA radioligand resulted in a temporary regression of the metastases.

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.

Most common health problems in general practice among adolescents, and young adults' survivors of lymphoma: a register-based cohort study in Norway.

BACKGROUND: The aim was to investigate the distribution of health problems in general practice (GP) among adolescent and young adult (AYA) survivors of lymphoma and to compare problem rates with the general population. METHODS: All GP consultations between 2006 and 2020 were identified from the national GP claims register. Diseases and complaints presented 3-10 years after the cancer diagnosis were identified using the International Classification of Primary Care codes (ICPC-2) and compared by applying logistic regression models, presented with odds ratio (OR) and 95%CI. RESULTS: A total of 2,500,557 AYAs, of whom 1105 were diagnosed with lymphoma, and over 50 million GP consultations were included. The most common causes of consultation among AYA survivors of lymphoma were related to Hodgkin's disease (13%), pregnancy (11%), respiratory diseases (9%), psychological problems (8%), musculoskeletal system (6%) and fatigue (4%). Almost all these problems were significantly higher among AYA lymphoma survivors compared to the general population (OR ranging from 1.1 to 1.5). CONCLUSION: Compared to the general population, young lymphoma survivors have increased contact with the GP for a considerable number of health problems for up to 10 years post-diagnosis. This emphasizes the importance of robust follow-up and a good flow of information between hospital and primary care.

Inflammatory serum markers and risk and severity of prostate cancer: The PROCA-life study.

Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive-CRP (hs-CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA-life), a prospective population-based cohort study, 7,356 men were included. Prediagnostic WBC and hs-CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow-up. During a mean 11.8 years follow-up, 509 men developed prostate cancer (mean age at diagnosis 71.7 years). Multivariable Cox proportional hazard regression models were used to study whether individual biomarkers (WBC, hs-CRP), a combined score based on analyte tertiles (score range 2-6), or change in CRP were associated with risk and severity of prostate cancer. We observed a positive dose-response relationship between hs-CRP and prostate cancer risk with a Hazard Ratio (HR) per mg/l of 1.3, 95% CI 1.00-1.07. Men with an increase in hs-CRP between two measurements (Δhs-CRP) of ≥1.00 mg/l had a 36% increased risk of prostate cancer (HR 1.36, 95% CI 1.02-1.82), compared to men with no change or decrease in hs-CRP. Men with a systemic inflammatory score of 5 or 6 had a 68% higher risk of being diagnosed with metastatic disease (HR 1.68, 95% CI, 1.04-2.73) compared to men with lower scores. Our study supports that hs-CRP including repeated measurements alone or in combination with WBC may be a useful inflammation-related biomarker for prostate cancer risk and prognosis.

Lifestyle behavior among lymphoma survivors after high-dose therapy with autologous hematopoietic stem cell transplantation, assessed by patient-reported outcomes.

Introduction: High-dose therapy with autologous stem cell transplantation (HD-ASCT) is associated with an increased risk of late effects. Our aim was to assess lifestyle behavior and factors associated with unhealthy lifestyle among HD-ASCT-treated lymphoma survivors (HD-ASCT-LS). Materials and methods: We conducted a national cross-sectional study of HD-ASCT-LS treated during 1987-2008. Among 399 eligible participants, 312 (78%) completed patient-reported outcome measures (PROMs) on lifestyle behavior (physical activity, overweight, smoking and alcohol consumption), chronic fatigue (CF) and somatic and mental illness. We assessed lifestyle according to WHO recommendations. Multivariable logistic regression models were used to study associations between variables. A comparison to the general population was performed. Results: Mean age at survey was 54.6 years, 60% were men, 55% sedentary, 55% overweight, 18% smokers and 5% had unhealthy alcohol consumption. Being sedentary was positively associated with older age, low household income, CF and higher somatic burden (≥4 self-reported somatic conditions). Overweight was positively associated with male gender and negatively associated with increased number of chemotherapy regimens prior to HD-ASCT. Current smoking was positively associated with living alone and CF, and negatively associated with older age. Male gender, CF and higher somatic burden increased the risk of an unhealthier lifestyle whereas the increased number of chemotherapy regimens prior to HD-ASCT decreased the risk. HD-ASCT-LS were significantly less sedentary, less overweight, and had a lower likelihood of smoking than the controls. Discussion: Assessed by PROMs, unhealthy habits were frequent among HD-ASCT-LS and associated with comorbidity. Nevertheless, compared with controls significantly more HD-ASCT-LS met lifestyle recommendations. These results indicate that the HD-ASCT-LS may consist of two groups, the adhering group with less comorbidity and the non-adhering group with more comorbidity. Our findings illustrate the necessity of recommendations and support for improving health-related behavior in cancer survivorship plans in order to empower survivors in their life beyond cancer.

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.

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.

Expression of miR-24-1-5p in Tumor Tissue Influences Prostate Cancer Recurrence: The PROCA-life Study.

The role of miR-24-1-5p and its prognostic implications associated with prostate cancer are mainly unknown. In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), all men had a general health examination at study entry and were followed between 1994 and 2016. Patients with available tissue samples after a prostatectomy with curative intent were identified (n = 189). The tissue expression of miR-24-1-5p in prostate cancer was examined by in situ hybridization (ISH) in tissue microarray (TMA) blocks by semi-quantitative scoring by two independent investigators. Multivariable Cox regression models were used to study the associations between miR-24-1-5p expression and prostate cancer recurrence. The prostate cancer patients had a median age of 65.0 years (range 47−75 years). The Cancer of the Prostate Risk Assessment Postsurgical Score, International Society of Urological Pathology grade group, and European Association of Urology Risk group were all significant prognostic factors for five-year recurrence-free survival (p < 0.001). Prostate cancer patients with a high miR-24-1-5p expression (≥1.57) in the tissue had a doubled risk of recurrence compared to patients with low expression (HR 1.99, 95% CI 1.13−3.51). Our study suggests that a high expression of miR-24-1-5p is associated with an increased risk of recurrence of prostate cancer after radical prostatectomy, which points to the potential diagnostic and therapeutic value of detecting miR-24-1-5p in prostate cancer cases.

Sexual dysfunction is prevalent in female lymphoma survivors after autologous stem-cell transplantation and is associated with younger age, chronic fatigue, and mental distress.

Sexual function in female lymphoma survivors after high-dose therapy with autologous stem-cell transplantation (auto-SCT) is largely unstudied. Female lymphoma survivors treated with auto-SCT in Norway 1987-2008 were eligible participants (n = 157). A multi-item questionnaire including a complete Sexual Activity Questionnaire was returned by 70% (n = 110) of the women. A comparison to age-matched normative controls was performed. Sexual inactivity was equal among survivors and controls. The survivors reported personal issues more frequent as reason for inactivity compared with controls (44% vs. 28%, p = 0.04). The sexually active survivors reported more sexual discomfort, greater reduction in frequency of sexual activity, and more sex-related tiredness compared with controls (p value and effect size [95% confidence interval]; p ≤ 0.001, 0.70 [0.44, 0.97], p = 0.03, -0.29 [-0.55, -0.03] and p ≤ 0.001, 0.64 [0.37, 0.90], respectively). Sexual activity was related to older age (odds ratio (OR) 0.58 [0.43, 0.82] per 10 years), being in a relationship (OR 28.6 [6.9, 118.9]) and hormonal replacement therapy (OR 6.0 [1.49, 24.2]). Tiredness in relation to sexual activity was associated with younger age, chronic fatigue and mental distress. Sexual inactivity due to personal issues was more frequent and among those sexually active, a higher rate of sexual dysfunction exists among auto-SCT survivors compared with controls. Hence, sexual function should be addressed at regular timepoints during the cancer trajectory.

Sexual function in long-term male lymphoma survivors after high-dose therapy with autologous stem-cell transplantation.

Reduced sexual function may have negative implications on health related quality of life among lymphoma survivors. A national cross-sectional study among long-term lymphoma survivors after high-dose therapy with autologous stem-cell transplantation auto-SCT treated during 1987-2008 was conducted in 2012-2014. The current study explored sexual functioning among these survivors. Sixty-six percent (n = 159) of eligible men with complete questionnaire data were included, median age was 55 years. The Brief Sexual Function Inventory (BSFI) was used to assess sexual function and sexual satisfaction, compared with age-matched controls. In addition, sexual problems were defined based on predetermined cutoff values for BSFI domain scores. Sexual drive and erections firm enough to have sexual intercourse were reported to be present only a few days or less last month among 30% and 41% of survivors, respectively. Sexual satisfaction was reported by 39% of survivors. The survivors had significantly lower scores on all BSFI domains and an increased risk of problems with sexual drive and erection compared with controls. In multivariable models, cardiovascular disease was significantly associated with worse erectile function, while age > 55 years, chronic fatigue, and physical inactivity were significantly associated with lower sexual functioning overall. Chronic fatigue and anxiety were related to lower sexual satisfaction.

Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour: A Population-based Study from the Swedish Norwegian Testicular Cancer Group.

BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND. DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection.

Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry.

PURPOSE: Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking. PATIENTS AND METHODS: We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET. RESULTS: Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%. CONCLUSION: FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone.

Beyond stage I germ cell tumors: current status regarding treatment and long-term toxicities.

Approximately 20% to 40% of patients with germ-cell tumors (GCT) will need advanced medical treatment because of relapse or initial metastatic disease. The survival and recommended treatment for men with metastatic disease varies according to histology, primary and metastatic sites, and the level of prechemotherapy tumor markers. For patients with a good prognosis, three cycles of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide, and cisplatin are recommended. For patients with intermediate- and poor prognosis, four cycles of bleomycin, etoposide, and cisplatin remains the preferred treatment option, although a switch to a more intensive regimen can be considered a new alternative. A major advance in salvage therapy for GCT in the last 5 years was the development of a new risk classification system. Initial salvage treatment includes both high-dose chemotherapy and standard-dose chemotherapy. There is clear consensus that patients with residual masses larger than 1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND); however, the role of PC-RPLND in patients with serologic and radiographic complete response to first-line chemotherapy is controversial. The rationale for PC-RPLND in patients with small residual masses is discussed, and only a small minority of advanced nonseminoma GCT (NSGCT) patients are suitable candidates for observation after first-line chemotherapy. Post-treatment long-term toxicity has emerged as an important issue for GCT survivors. Examples of late effects are secondary nongerm-cell cancers and cardiovascular disease, which represent the most severe and potentially life-threatening effects of cancer treatment. Follow-up of cancer survivors should include recommendations for maintaining a healthy lifestyle to reduce the risk of serious long-term and late effects of treatment.

A controlled study of risk factors for disease and current problems in long-term testicular cancer survivors.

INTRODUCTION: To compare risk factors for disease and current problems in long-term testicular cancer survivors (TCSs) and age-matched population-based controls (NORMs). METHODS: The study was cross-sectional and concerned 1,291 Norwegian TCSs followed up after a mean of 11 years, and 6,455 NORMs. Both TCSs and NORMs completed questionnaires and had a clinical examination. Indices for risk factors and current problems were calculated. Outcome measures were: visits to general practitioners last year, poor self-rated health, and poor quality of life (QoL). RESULTS: The mean risk score was significantly lower and the mean current problem score significantly higher in TCSs compared to NORMs without reaching clinical significance. The risk for future fatal cardiac events did not differ between the groups. TCSs had a higher risk for visiting a general practitioner than NORMs (OR 3.58, 95% CI 3.09-4.15), while no significant difference was observed for self-rated health. Poor QoL in TCSs was significantly associated with more current problems than risk factors. Previous treatment for mental problems, presence of severe somatic disease and musculo-skeletal problems were significantly associated with all three outcome measures. Musculo-skeletal problems were most strongly associated with visits to general practitioners among TCSs. CONCLUSIONS: Several risk factors for preventive clinical interventions and current problems that eventually should be treated were identified in TCSs. IMPLICATIONS FOR CANCER SURVIVORS: TCSs show several risk factors and current problems that are relevant for visits to general practitioners, poorer self-rated health, and poorer QoL. These should get attention from health personnel caring for TCSs.