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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.
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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.
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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.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Nefrectomía/efectos adversos , Nefrectomía/métodos , Resultado del TratamientoRESUMEN
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.
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Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Testiculares/patología , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/terapia , Estudios Prospectivos , Adulto , Adulto Joven , Tomografía Computarizada por Rayos X , Escisión del Ganglio Linfático , Biomarcadores de Tumor , Persona de Mediana Edad , Adolescente , Metástasis Linfática , Suecia/epidemiologíaRESUMEN
INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. PATIENT AND METHODS: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. RESULTS: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. CONCLUSIONS: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.
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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.
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Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/cirugía , Neoplasias Testiculares/patología , Estudios Prospectivos , Reproducibilidad de los Resultados , Espacio Retroperitoneal/cirugía , Escisión del Ganglio Linfático/métodos , Neoplasias de Células Germinales y Embrionarias/patología , FibrosisRESUMEN
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.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Timidina Quinasa , BiomarcadoresRESUMEN
INTRODUCTION: Most patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP. PATIENTS AND METHODS: We performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003-2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis. RESULTS: Some 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4-6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51-72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65-14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04-1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01-20.3, p = 0.049). CONCLUSION: PEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.
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Insuficiencia Pancreática Exocrina , Cálculos Renales , Pancreatitis Crónica , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/epidemiología , Insuficiencia Pancreática Exocrina/complicaciones , Insuficiencia Pancreática Exocrina/epidemiología , Factores de Riesgo , Cálculos Renales/complicaciones , Cálculos Renales/epidemiologíaRESUMEN
OBJECTIVE: Patients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort. MATERIALS AND METHODS: A total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models. RESULTS: Age, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69-5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44-0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71-0.95, p < 0.001) than patients treated with radical nephrectomy. CONCLUSIONS: Age, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.
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Carcinoma de Células Renales , Neoplasias Renales , Femenino , Humanos , Masculino , Anciano , Carcinoma de Células Renales/cirugía , Suecia , Neoplasias Renales/cirugía , Pronóstico , Modelos de Riesgos Proporcionales , Nefrectomía/efectos adversos , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
AIM: Estimate the effect of Radium-223 (Ra-223) on the incidence of bone fractures, prostate cancer death, and all-cause death compared with other standard treatments for metastatic, castration-resistant prostate cancer (mCRPC). METHODS: Using a cohort design, we estimated the effect of Ra-223 on the risk of bone fractures, all-cause and prostate cancer-specific mortality across different lines of treatment for mCRPC using Prostate Cancer data Base Sweden (2013-2018). The comparator group comprised other standard treatments for mCRPC. We used 36-month risk differences and hazard ratios (HRs) as effect estimates. RESULTS: The number of eligible individuals was 635, 453, 262, and 84 for the first-, second-, third-, and fourth-line cohorts, respectively. When compared Ra-223 to other standard treatments, the difference in the 36-month risk of fracture was 6% (95% confidence interval [CI], -7% to 18%) in the first-line cohort (n = 635) and 8% (95% CI, -7% to 18%) in the second-line cohort (n = 453). The number of fractures in the third-/fourth-line cohorts was too small for an adjusted comparison. The difference in 36-month mortality was higher in the first-line cohort 13% (95% CI, -3% to 31%), but lower in the second- and third-/fourth-line cohorts-8% (95% CI, -23% to 7%) and -14% (95% CI, -21% to 16%) respectively. Most deaths were due to prostate cancer. CONCLUSION: Results suggest that the difference in the risk of fractures is small, if any. A difference in the risk of mortality may be present in first-line treatment, but a decreased risk of mortality was observed in second and later lines of treatment. The results on mortality need to be considered in the context of potential unmeasured or residual confounding.
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Neoplasias Óseas , Fracturas Óseas , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Radio (Elemento)/uso terapéutico , Suecia/epidemiología , Fracturas Óseas/inducido químicamente , Fracturas Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Neoplasias Óseas/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To examine the association between surgical waiting times (SWTs) and all-cause mortality (ACM) in non-metastatic patients with RCC, in relation to tumour stage. PATIENTS AND METHODS: This nation-wide population-based cohort study included 9,918 M0 RCC patients registered in the National Swedish Kidney Cancer Register, between 2009 and 2021, followed-up for ACM until 9 December 2021, and having measured SWTs. The associations between primarily SWTs from date of radiological diagnosis to date of surgery (WRS) and secondarily SWTs from date of radiological diagnosis to date of treatment decision (WRT) and date of treatment decision to date of surgery (WTS), in relation to ACM, were analysed using Cox regression analysis, adjusted for clinical and demographic characteristics, stratified and unstratified according to T-stage. RESULTS: During a mean follow-up time of 5 years (49,873 person-years), 23% (n = 2291) of the patients died. The adjusted hazard ratio (AHR) for WRS (months) for all patients was 1.03 (95% confidence interval [CI] = 1.02-1.04; p < 0.001). When subdividing WRS on T-stage, the AHRs were 1.03 (95% CI = 1.01-1.04; p < 0.001) and 1.05 (95% CI = 1.02-1.08; p = 0.003) for stages T1 and T3, respectively, while non-significant for T2 (p = 0.079) and T4 (p = 0.807). Similar results were obtained for WRT and WTS. CONCLUSIONS: Prolonged SWTs significantly increased the risk of early overall death among patients with RCC. The increased risk of early death from any cause show the importance of shortening SWTs in clinical work of patients with this malignant disease.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/secundario , Estudios de Cohortes , Listas de Espera , Neoplasias Renales/patología , Modelos de Riesgos Proporcionales , Nefrectomía/métodos , Estudios Retrospectivos , Estadificación de NeoplasiasRESUMEN
Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design setting and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients). Outcome measurements and statistical analysis: The primary endpoints were 18-mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests. Results and limitations: The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42-1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy. Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.
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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.
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Neoplasias de la Próstata , Timidina Quinasa , Biomarcadores , Biomarcadores de Tumor , Estudios de Casos y Controles , Humanos , MasculinoRESUMEN
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.
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Neoplasias de Células Germinales y Embrionarias , Neoplasias Retroperitoneales , Teratoma , Neoplasias Testiculares , Humanos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Masculino , Neoplasia Residual/cirugía , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Retroperitoneales/cirugía , Suecia/epidemiología , Teratoma/cirugía , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/patología , Neoplasias Testiculares/cirugíaRESUMEN
MicroRNA-371a-3p (miR371) has been suggested as a sensitive biomarker in testicular germ cell cancer (TGCC). We aimed to compare miR371 with the classical biomarkers α-fetoprotein (AFP) and ß-human chorionic gonadotropin (hCGß). Overall, 180 patients were prospectively enrolled in the study, with serum samples collected before and after orchiectomy. We compared the use of digital droplet PCR (RT-ddPCR) with the quantitative PCR used by others for detection of miR371. The novel RT-ddPCR protocol showed high performance in detection of miR371 in serum samples. In the study cohort, miR371 was measured using RT-ddPCR. MiR371 detected CS1 of the seminoma and the non-seminoma sub-types with a sensitivity of 87% and 89%, respectively. The total sensitivity was 89%. After orchiectomy, miR371 levels declined in 154 of 159 TGCC cases. The ratio of miR371 pre- and post-orchiectomy was 20.5 in CS1 compared to 6.5 in systemic disease. AFP and hCGß had sensitivities of 52% and 51% in the non-seminomas. MiR371 is a sensitive marker that performs better than the classical markers in all sub-types and clinical stages. Especially for the seminomas CS1, the high sensitivity of miR371 in detecting TGCC cells may have clinical implications.
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MicroARNs/sangre , MicroARNs/genética , Neoplasias de Células Germinales y Embrionarias/sangre , Neoplasias de Células Germinales y Embrionarias/cirugía , Orquiectomía , Reacción en Cadena de la Polimerasa , Neoplasias Testiculares/sangre , Neoplasias Testiculares/cirugía , Adolescente , Adulto , Biomarcadores de Tumor/sangre , Gonadotropina Coriónica/sangre , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/genética , Estudios Prospectivos , Estabilidad del ARN/genética , Reproducibilidad de los Resultados , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Carga Tumoral , Adulto Joven , alfa-Fetoproteínas/análisisRESUMEN
BACKGROUND: Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal-related events in routine clinical practice. METHODS: This cohort study in Denmark, Norway, and Sweden in 2011-2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab-switch cohort (DESC). The authors estimated 1- to 5-year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS: There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow-up was 19.8, 12.9, and 13.3 months, respectively. The 5-year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%-7.3%) in the DEIC, 1.4% (95% CI, 0.8%-2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%-10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person-years were 3.0 (95% CI, 2.3-3.7), 1.0 (95% CI, 0.6-1.5), and 4.3 (95% CI, 2.8-6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS: This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country. LAY SUMMARY: Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)-death of a jawbone-is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab- or zoledronic acid-treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Neoplasias Óseas , Osteonecrosis de los Maxilares Asociada a Difosfonatos/tratamiento farmacológico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/epidemiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Conservadores de la Densidad Ósea/efectos adversos , Neoplasias Óseas/secundario , Estudios de Cohortes , Dinamarca/epidemiología , Denosumab/efectos adversos , Difosfonatos/efectos adversos , Humanos , Masculino , Suecia , Ácido Zoledrónico/efectos adversosRESUMEN
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.
Asunto(s)
Detección Precoz del Cáncer/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Anciano , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Recently, the CARMENA and SURTIME studies, suggested that upfront cytoreductive nephrectomy (CN) should be abandoned for patients with intermediate and high-risk metastatic renal cell carcinoma (mRCC). However, CN remains an indication in low-risk and when immediate systemic treatment is not required. The aim was to evaluate the long-term overall survival (OS) in patients with primary mRCC, based on the first line treatment. METHODS: There were 1483 patients with primary mRCC in the National Kidney Cancer Registry from 2005 to 2013. Data on primary treatment, TNM stage, RCC type, tumor size, patient age and sex were extracted. Survival time was calculated from time of diagnosis to time of death or until July 2019. Mann-Whitney U and Chi-square tests, the Kaplan-Meyer method and Cox regression analyses were used. RESULTS: Patients primary treated with CN had a significantly longer OS (p < .001) than patients primary treated with systemic therapy or palliation. In a Cox regression multivariate analysis, the hazard ratio for CN compared with no CN was 1.600, 95%Ci (1.492 - 1.691), p < .001. Also occurrence of lymph node metastases, T-stage, patients age and year of diagnosis, remained as independent predictors of OS. CONCLUSION: Patients primary treated with CN survived significantly longer than patients primary treated with systemic therapy or palliation, in all age groups. CN was an important first-line treatment option in mRCC patients.
Asunto(s)
Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Nefrectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/secundario , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
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.