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.

Ablative or Surgical Treatment for Small Renal Masses (T1a): A Single-Center Comparison of Perioperative Morbidity and Complications.

The purpose of this study is to evaluate the treatment safety of thermal ablation compared to surgical treatment of T1a tumors (small renal masses) at a high-volume center. We conducted an observational single-center study based on data collected form the National Swedish Kidney Cancer Register (NSKCR) between 2015 and 2021. In total, 444 treatments of T1a tumors were included. Patients underwent surgery (partial or total nephrectomy) or ablative treatment-radiofrequency ablation (RFA) or microwave ablation (MWA). Patient characteristics were retrieved from patient records, and tumor complexity was estimated from pre-interventional CT scans. The odds ratio (OR) of suffering from a severe surgical complication following ablative treatment was estimated using a logistic regression model adjusted for age, BMI, ASA physical status classification, smoking status and RENAL nephrometry score. The frequency of severe surgical complications was 6.3% (16/256 treatments) after surgical intervention and 2.1% (4/188 treatments) following ablative treatment. Our primary hypothesis that ablative treatment is associated with a lower risk of severe surgical complications is supported by the results (OR 0.39; 0.19-0.79; p = 0.013). When adjusting for age, smoking status, ASA score, BMI score and RENAL nephrometry score, we see an even greater difference between the two groups (OR 0.34; 0.17-0.68; p = 0.002). Our study was limited by the differences in patient and tumor characteristics between the two compared groups and the study design. If oncological outcomes are found to be comparable, ablative treatment should be considered as a first-line treatment for all small renal masses.

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.

Serum thymidine kinase 1 concentration as a predictive biomarker in prostate cancer.

BACKGROUND: Thymidine kinase 1 (TK1) recycles DNA before cell division. We do not know if baseline blood concentrations of TK1 predict death in prostate cancer within 30 years. Our objective is to determine if there is an association between baseline levels of TK1 and future prostate cancer-specific mortality. METHODS: With a "proof of concept" approach, we performed a nested case-control study among 1782 individuals screened for prostate cancer between 1988 and 1989. The concentration of TK1 was measured in frozen serum from 330 men, 36 of whom have died of prostate cancer. The primary endpoint was prostate cancer-specific mortality and outcomes after 30 years were analyzed using logistic regression modeling odds ratios (Ors). RESULTS: The estimated OR (adjusted for age) for dying from prostate cancer among the men who had a TK1 value in the upper tertile was 2.39 (95% confidence interval 1.02-5.63). The corresponding OR, regardless of the cause of death, was 2.81 (1.24-6.34). CONCLUSIONS: High levels of TK1 predicts death in prostate cancer within 30 years of follow-up.

Association between one-time prostate-specific antigen (PSA) test with free/total PSA ratio and prostate cancer mortality: A 30-year prospective cohort study.

OBJECTIVES: To explore if there is a long-term association between baseline prostate-specific antigen (PSA), including free/total PSA ratio and long-term (30-year) risk for prostate cancer death. SUBJECTS AND METHODS: In all, 1782 men were screened for prostate cancer through PSA analysis. Some years later, frozen plasma samples were used to calculate the ratio of free to total PSA (f/t PSA). At 30-year follow-up, baseline PSA and f/t PSA were compared with recent data extracts from the Swedish Cause of Death Registry and Swedish Cancer Registry. PSA values and f/t PSA values were treated as continuous variables in a multivariable analysis and also stratified according to their distribution and useful clinical thresholds. RESULTS: Risk of death from prostate cancer after 30 years of follow-up was significantly increased with a higher baseline PSA level, with the hazard ratio being 1.04 (95% confidence interval 1.03-1.09) per increase of one unit of PSA. Adding f/t PSA increased the model's ability to discriminate (concordance index 0.84-0.88). Men with PSA levels <1.0 ng/mL had a very low long-term risk of prostate cancer death (1.2% risk). An f/t PSA ≥ 0.25 extended the low-risk range to PSA < 2.0 ng/mL (1.5% risk). CONCLUSION: Prostate-specific antigen testing can be carried out less frequently or can be discontinued in men aged 55-70 years if their PSA levels are <2.0 ng/mL and the f/t PSA is ≥0.25.

Association between dihydrotestosterone and long-term risk for prostate cancer mortality: A prospective cohort study.

BACKGROUND: The androgen metabolism plays an important role in the progression of prostate cancer. Contradictory to what one might assume given the androgenic potency of dihydrotestosterone (DHT) there are indications that high DHT levels protect from prostate cancer. We want to determine whether there is a long-term association between baseline levels of DHT and death from prostate cancer. METHOD: During the years 1988 and 1989, 1782 men out of 2400 invited were screened for prostate cancer. The invited men were randomly selected from a background population of more than 27 000 men. Serum levels of DHT were analyzed for all 65 men diagnosed in the trial and 130 controls from the same cohort without any signs of prostate cancer. In this study we evaluate outcomes for the whole cohort (n = 195), the men without clinical signs of prostate cancer at beginning of follow up (n = 130) and men with screening detected cancer (n = 65). The cohort was followed up after 30 years and data from the Swedish Cause of Death Registry and the Swedish Cancer Registry were extracted. Hazard ratios (HRs) were calculated using Cox regression models. RESULT: High DHT levels were positively correlated to a lower risk for prostate cancer death in the entire cohort: HR = 0.44 (0.25-0.77 95% confidence interval [CI]). The positive correlation remained significant for the subgroup analysis. HR for the men enrolled in the study without any clinical signs of prostate cancer was 0.25 (0.07-0.88 95% CI) and for the men with a prostate cancer diagnosis at time of inclusion: HR = 0.50 (0.26-0.94 95% CI). CONCLUSION: DHT is negatively associated with long-term prostate cancer death regardless of clinical presentation at time of inclusion.

Long-Term Outcome of a Single Intervention Population Based Prostate Cancer Screening Study.

PURPOSE: We evaluated the long-term effect of screening for prostate cancer. MATERIALS AND METHODS: In 1988 we randomly selected 2,400 men from a background population of 27,464 men. The 2,400 men were invited to undergo screening, of whom 1,779 (74%) accepted and were examined with digital rectal examination, ultrasound and prostate specific antigen measurement. Biopsy was performed if there were suspicious findings on ultrasound or digital rectal examination, or prostate specific antigen was greater than 10 ng/ml. The subpopulations have now been reassessed after 20 years. RESULTS: Participants had a decreased overall mortality rate compared to the source population (IRR 0.93, 95% CI 0.86-0.98). Nonparticipants had an increased overall mortality rate (IRR 1.25, 95% CI 1.14-1.37). There was no difference between the groups in prostate cancer specific survival. The incidence of prostate cancer remained higher in the screened population throughout followup. CONCLUSIONS: A single screening intervention in men 50 to 75 years old using prostate specific antigen, digital rectal examination and transrectal ultrasound, and a prostate specific antigen cutoff of 10 ng/ml for biopsy carried a significant risk of prostate cancer detection without a concomitant reduction in prostate cancer specific mortality after 20 years. This intervention should not be considered for public screening. Nonparticipants were at greater risk for death of all causes. In addition to being a single intervention trial, the limitations of this study include an outdated prostate specific antigen cutoff for biopsy. Despite the outdated screening method the source population failed to reach the same level of prostate cancer incidence as the screened population even after 20 years.