<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02229916</url>
  </required_header>
  <id_info>
    <org_study_id>SG359/13</org_study_id>
    <nct_id>NCT02229916</nct_id>
  </id_info>
  <brief_title>Swiss Austrian German Testicular Cancer Cohort Study - SAG TCCS</brief_title>
  <acronym>SAG TCCS</acronym>
  <official_title>Swiss Austrian German Testicular Cancer Cohort Study - SAG TCCS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. med. Christian Rothermundt</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Testicular Cancer Study Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cantonal Hospital of St. Gallen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The majority of testicular cancer patients can be cured with cisplatin-based chemotherapy.&#xD;
      Mortality has been reduced even more within the last 15 years due to the stringent&#xD;
      application of standard chemotherapy followed by resection of residual disease. This is a&#xD;
      positive development considering that testicular cancer usually affects young men. Active&#xD;
      surveillance has become an acceptable and widely used strategy in stage I testicular cancer.&#xD;
      Thus, it is important to follow these patients in a standardized way and to adhere to a&#xD;
      rationale surveillance strategy. There is no international consensus regarding follow-up of&#xD;
      testicular cancer patients. Stratification according to risks and patterns of relapse would&#xD;
      allow to tailor follow-up schedules, aiming at early identification of relapse without&#xD;
      causing unnecessary harm by using excessive radiation in these young long-term survivors.&#xD;
      Follow-up procedures should not only aim at detecting relapse, but also long-term side&#xD;
      effects from therapy, including hypogonadism, metabolic syndrome, cardiovascular disease and&#xD;
      secondary malignancies. The Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS)&#xD;
      will comprise consecutive newly diagnosed testicular cancer patients and is the first study&#xD;
      to prospectively evaluate the initial indictor of relapse in testicular cancer patients, the&#xD;
      frequency and pattern of relapse and document long-term toxicities of the treatment&#xD;
      (cardiovascular, gonadal, hearing impairment, renal function and second malignancies) and&#xD;
      psychosocial aspects. This cohort study will determine the relevance of each test performed&#xD;
      routinely during follow-up. The collected data will have direct implications for the care of&#xD;
      patients with testicular cancer and inform future adaptations of follow-up recommendations.&#xD;
      The dataset will give information on baseline factors of testicular cancer patients patients,&#xD;
      current treatment strategies in Switzerland, Austria and Germany, outcome and late sequelae.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives&#xD;
&#xD;
      Primary objective&#xD;
&#xD;
      The primary objective is to determine the diagnostic performance and the clinical impact of a&#xD;
      variety of tests, including conventional radiographs, computer tomographies (CT), abdominal&#xD;
      ultrasound, serum tumour markers (AFP, beta-HCG and LDH) and clinical signs and symptoms&#xD;
      aimed at early detection of relapse after curative therapy with documented complete&#xD;
      remission.&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
      Diagnostic performance:&#xD;
&#xD;
        1. To determine the rate of relapses detected on chest x-ray in seminoma patients.&#xD;
&#xD;
        2. To determine the rate of false positive abnormalities on CT scan and of false positive&#xD;
           tumour marker elevations not due to seminomatous or non-seminomatous germ cell tumour&#xD;
           relapses but due to other processes.&#xD;
&#xD;
        3. To determine the modality to rule out testicular cancer relapse in patients with false&#xD;
           positive index tests.&#xD;
&#xD;
           Pattern of care:&#xD;
&#xD;
        4. To assess patient characteristics at baseline and at the time-point of relapse&#xD;
           detection.&#xD;
&#xD;
        5. To determine the rate of stage I seminoma and non-seminoma patients undergoing active&#xD;
           surveillance.&#xD;
&#xD;
        6. To obtain an overview of treatment and follow-up strategies in germ cell cancer patients&#xD;
           in Switzerland.&#xD;
&#xD;
           Outcome:&#xD;
&#xD;
        7. To collect data on treatment sequelae following testicular cancer treatment in terms of&#xD;
           organ function, cardiovascular risk factors, sexual health and socioeconomic aspects.&#xD;
&#xD;
        8. To determine the rate of intermediate and poor-prognosis disease at relapse.&#xD;
&#xD;
        9. To determine the rate of offspring spontaneously conceived after testicular cancer&#xD;
           treatment.&#xD;
&#xD;
      Design&#xD;
&#xD;
      Prospective cohort study&#xD;
&#xD;
      Centres All urologists, radiooncologists and oncologists are motivated to enrol their&#xD;
      patients. We will aim at enrolling the majority of patients treated and followed in private&#xD;
      practice.&#xD;
&#xD;
      Patients Consecutive patients with testicular cancer of any type and any stage (incident&#xD;
      cases). Testicular cancers are generally classified as seminomatous (seminoma) and&#xD;
      nonseminomatous germ cell tumours (non-seminoma) of the testis. Mixed germ cell tumours&#xD;
      belong to the group of non-seminomas. The stage of disease and the choice of treatment&#xD;
      (active surveillance vs. chemotherapy vs. radiotherapy) define the risk of relapse, the&#xD;
      pattern of relapse and the long-term toxicities. Staging in testicular cancer is performed&#xD;
      according to the American Joint Committee on Cancer (AJCC) primary tumor, regional nodes,&#xD;
      metastasis (TNM) staging system for testis cancer. Metastatic testicular cancers are&#xD;
      classified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) risk&#xD;
      groups.&#xD;
&#xD;
      Clinical outcome&#xD;
&#xD;
      Relapse of testicular cancer will be defined as rising concentrations of serum&#xD;
      alphafetoprotein (AFP) above the upper limit of normal (typically &gt; 13 μg/l) and/or human&#xD;
      chorionic gonadotropin (HCG) above the upper limit of normal (typically &gt; 5 U/l) and/or&#xD;
      lactate dehydrogenase (LDH) above the upper limit of normal and confirmation of this rise in&#xD;
      a second test four weeks later and/or radiographic evidence of metastatic disease in typical&#xD;
      locations, and/or the presence of active germ cell tumour established by biopsy, whatever&#xD;
      comes first.&#xD;
&#xD;
      Index tests&#xD;
&#xD;
      The following tests will be performed (ordered according to their burden for patients and&#xD;
      cost): symptom assessment, physical examination, tumour marker measurement, chest x-ray,&#xD;
      abdominal ultrasound and CT scan of abdomen and pelvis.&#xD;
&#xD;
      Procedures&#xD;
&#xD;
      Follow-up will be performed according to the mandatory follow-up schedule by a physician who&#xD;
      has substantial experience in the treatment and surveillance of patients with germ cell&#xD;
      tumours. Follow-up comprises thorough assessment of medical history and patients' symptoms&#xD;
      with a focus on pain, appetite, fatigue, sexual function and activities of daily living;&#xD;
      physical examination includes lung auscultation, abdominal, axillary, supra- and&#xD;
      infradiaphragmatic regional lymph nodes and testicular palpation; serum tumour marker&#xD;
      measurement: AFP, HCG and LDH; chest x-ray and abdominal ultrasound or CT scan. Even though&#xD;
      the role of LDH in the follow-up is debatable, due to limited sensitivity and specificity and&#xD;
      a high rate of false-positive tests, it can contribute to identify relapse in a significant&#xD;
      number of cases, as shown in a recent publication. All the laboratory and radiological tests&#xD;
      are performed independently and results are not made available to the investigator prior to&#xD;
      symptom assessment and physical examination. In addition we will ascertain cardiovascular&#xD;
      risk factors (smoking status, lipid profile, bodymass index, fasting glucose etc.), renal&#xD;
      function, testosterone level, follicle stimulating hormone (FSH) level, lutenizing hormone&#xD;
      (LH) level, and socioeconomic characteristics (education, employment, partnership) in annual&#xD;
      intervals.&#xD;
&#xD;
      Statistics&#xD;
&#xD;
      Sample size considerations&#xD;
&#xD;
      There are approximately 400 newly diagnosed testicular cancer patients in Switzerland per&#xD;
      year. In Germany the annual testicular cancer incidence is about 4000. We aim at including&#xD;
      approximately 300 patients per year in Switzerland over a duration of 3 years, with a total&#xD;
      number of 900 patients. We are also aiming at registration of 2000 patients per year in&#xD;
      Germany. Looking at the Swiss cohort, with an estimated 15% rate of relapses over a follow-up&#xD;
      duration of two years, this will yield approximately 135 cases with relapse. This number will&#xD;
      yield satisfactory statistical precision. An assumed sensitivity of 50% and a specificity of&#xD;
      95% for Beta-HCG, for example, to detect a relapse will yield a positive likelihood ratio&#xD;
      (LR) of 10 and a negative likelihood ratio of 0.53. Corresponding 95% confidence intervals&#xD;
      will be 42 to 58% for sensitivity, 93 to 97% for specificity, 7.0 to 14.2 for the positive&#xD;
      likelihood ratio and 0.44 to 0.62 for the negative likelihood ratio. An assumed sensitivity&#xD;
      of 37% and a specificity of 99% for CT scans, for example, to detect a relapse will yield a&#xD;
      positive likelihood ratio of 37 and a negative likelihood ratio of 0.64. Corresponding 95%&#xD;
      confidence intervals will be 29 to 45% for sensitivity, 98 to 100% for specificity, 17.7 to&#xD;
      77.4 for the positive likelihood ratio and 0.56 to 0.72 for the negative likelihood ratio.&#xD;
&#xD;
      Measures of diagnostic accuracy will be determined in relation to the occurrence and&#xD;
      timepoint of diagnosis of a relapse as specified above. Tests that were positive within the&#xD;
      previous 8 weeks of established diagnosis of relapse will be considered as true positives,&#xD;
      tests that remained negative during this time period as false negatives. Conversely, tests&#xD;
      that were positive before this time period will be considered as false positives, and tests&#xD;
      that were negative before this period as true negatives. We will use a multi-level model with&#xD;
      random effects at the level of patients and time-points to estimate sensitivities and&#xD;
      specificities and likelihood ratios, with the data organised in long format, with each test&#xD;
      outcome (positive or negative) at each time-point represented by one line in the dataset,&#xD;
      determining for each time-point whether it is within the 8-week time-period previous to the&#xD;
      time-point of established diagnosis of relapse. The model takes into account the correlation&#xD;
      of multiple time-points and tests within patients. The positive LR indicates how much more&#xD;
      likely it is to find a positive test in patients with a relapse (sensitivity) as compared&#xD;
      with those without relapse (1-specificity). Conversely, the negative LR specifies how much&#xD;
      less likely it is to find a negative test in patients with relapse (1-sensitivity) as&#xD;
      compared to patients without (specificity). A test will be considered to provide clinically&#xD;
      relevant power to rule in or out a relapse if the positive and negative LRs are above 5 or&#xD;
      below 0.2, respectively. The test will be considered to have a strong power to rule in or out&#xD;
      a relapse if LRs are above 10 or below 0.1, respectively.&#xD;
&#xD;
      As measures of the clinical impact of the addition of more extensive tests, we will examine&#xD;
      the net re-classification improvement and the integrated discrimination improvement. The net&#xD;
      re-classification improvement through the addition of a more extensive test is defined as the&#xD;
      improvement of the probability of the appropriate classification of patients according to&#xD;
      relapse status (presence or absence of a relapse), which is afforded by the addition of the&#xD;
      more extensive test. This corresponds to the sum of differences in proportions of individuals&#xD;
      classified positive minus the proportion classified negative for individuals who develop&#xD;
      events, and the proportion of individuals classified negative minus the proportion classified&#xD;
      positive for individuals who do not develop events. The integrated discrimination improvement&#xD;
      is defined as the improvement in average sensitivity afforded by the addition of the more&#xD;
      extensive test minus the potential loss in specificity afforded by the addition of the more&#xD;
      extensive test. All analyses will be done using Stata, Release 11 (Stata Corp LP, College&#xD;
      Station, TX).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>December 2013</start_date>
  <completion_date type="Anticipated">December 2033</completion_date>
  <primary_completion_date type="Anticipated">December 2028</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>8 Years</target_duration>
  <primary_outcome>
    <measure>Mode of relapse detection</measure>
    <time_frame>8 years</time_frame>
    <description>Diagnostic performance and the clinical impact of a variety of tests, including conventional radiographs, computed tomographies (CT), abdominal ultrasound, serum tumour markers (AFP, beta-HCG and LDH) and clinical signs and symptoms aimed at early detection of relapse after curative therapy with documented complete remission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of relapses detected on chest x-ray in seminoma patients</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of false positive abnormalities on CT scan</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of false positive tumour marker elevations not due to seminomatous or non-seminomatous germ cell tumour relapses but due to other reasons</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient characteristics at baseline and at the time-point of relapse detection.</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of stage I seminoma and non-seminoma patients undergoing active surveillance.</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overview of treatment and follow-up strategies in germ cell cancer patients in Switzerland, Austria and Germany</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment sequelae following testicular cancer treatment in terms of organ function, cardiovascular risk factors, sexual health and socioeconomic aspects.</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of intermediate and poor-prognosis disease at relapse.</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of offspring spontaneously conceived after testicular cancer treatment.</measure>
    <time_frame>8 years</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">6900</enrollment>
  <condition>Testicular Neoplasms</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Consecutive patients with testicular cancer of any type and any stage and any age (incident&#xD;
        cases).&#xD;
&#xD;
        Testicular cancers are generally classified as seminomatous (seminoma) and nonseminomatous&#xD;
        germ cell tumours (nonseminoma) of the testis. Mixed germ cell tumours belong to the group&#xD;
        of non-seminomas. The stage of disease and the choice of treatment (active surveillance vs.&#xD;
        chemotherapy vs. radiotherapy) define the risk of relapse, the pattern of relapse and the&#xD;
        long-term toxicities. Staging in testicular cancer is performed according to the American&#xD;
        Joint Committee on Cancer (AJCC) TNM staging system for testis cancer [46]. Metastatic&#xD;
        testicular cancers are classified according to the International Germ Cell Cancer&#xD;
        Collaborative Group (IGCCCG) risk groups [47].&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
          -  Histologically proven seminomas or non-seminoma.&#xD;
&#xD;
          -  Seminoma: complete remission (CR) or lymph nodes (LN) &lt; 3cm or PET negative partial&#xD;
             remission (PR) or non-seminoma: CR.&#xD;
&#xD;
          -  Completion of treatment within the last 6 months.&#xD;
&#xD;
          -  Patient able and willing to attend for regular surveillance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-existent malignancy within 5 years.&#xD;
&#xD;
          -  Inability for any reason to comply with the trial investigations or follow-up&#xD;
             schedules.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christian Rothermundt, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cantonal Hospital of St. Gallen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kantonsspital St.Gallen; Onkologie/Haematologie</name>
      <address>
        <city>St.Gallen</city>
        <zip>9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Rothermundt, Dr. med.</last_name>
      <phone>+41 71 494 11 11</phone>
      <email>christian.rothermundt@kssg.ch</email>
    </contact>
    <investigator>
      <last_name>Christian Rothermundt, Dr. med.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>http://www.sag-tccs.com/</url>
    <description>Webpage with basic information on the cohort study and link to the electronic case report form (eCRF) portal</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Cantonal Hospital of St. Gallen</investigator_affiliation>
    <investigator_full_name>Dr. med. Christian Rothermundt</investigator_full_name>
    <investigator_title>PD Dr. med.</investigator_title>
  </responsible_party>
  <keyword>Testicular Neoplasms</keyword>
  <keyword>Testicular Cancer</keyword>
  <keyword>Cohort Study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Testicular Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02229916
org study id: SG359/13
nct id: NCT02229916
lead sponsor: 
collaborator: 
has dmc: Yes
The majority of testicular cancer patients can be cured with cisplatin-based chemotherapy.
      Mortality has been reduced even more within the last 15 years due to the stringent
      application of standard chemotherapy followed by resection of residual disease. This is a
      positive development considering that testicular cancer usually affects young men. Active
      surveillance has become an acceptable and widely used strategy in stage I testicular cancer.
      Thus, it is important to follow these patients in a standardized way and to adhere to a
      rationale surveillance strategy. There is no international consensus regarding follow-up of
      testicular cancer patients. Stratification according to risks and patterns of relapse would
      allow to tailor follow-up schedules, aiming at early identification of relapse without
      causing unnecessary harm by using excessive radiation in these young long-term survivors.
      Follow-up procedures should not only aim at detecting relapse, but also long-term side
      effects from therapy, including hypogonadism, metabolic syndrome, cardiovascular disease and
      secondary malignancies. The Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS)
      will comprise consecutive newly diagnosed testicular cancer patients and is the first study
      to prospectively evaluate the initial indictor of relapse in testicular cancer patients, the
      frequency and pattern of relapse and document long-term toxicities of the treatment
      (cardiovascular, gonadal, hearing impairment, renal function and second malignancies) and
      psychosocial aspects. This cohort study will determine the relevance of each test performed
      routinely during follow-up. The collected data will have direct implications for the care of
      patients with testicular cancer and inform future adaptations of follow-up recommendations.
      The dataset will give information on baseline factors of testicular cancer patients patients,
      current treatment strategies in Switzerland, Austria and Germany, outcome and late sequelae.
Objectives

      Primary objective

      The primary objective is to determine the diagnostic performance and the clinical impact of a
      variety of tests, including conventional radiographs, computer tomographies (CT), abdominal
      ultrasound, serum tumour markers (AFP, beta-HCG and LDH) and clinical signs and symptoms
      aimed at early detection of relapse after curative therapy with documented complete
      remission.

      Secondary objectives

      Diagnostic performance:

        1. To determine the rate of relapses detected on chest x-ray in seminoma patients.

        2. To determine the rate of false positive abnormalities on CT scan and of false positive
           tumour marker elevations not due to seminomatous or non-seminomatous germ cell tumour
           relapses but due to other processes.

        3. To determine the modality to rule out testicular cancer relapse in patients with false
           positive index tests.

           Pattern of care:

        4. To assess patient characteristics at baseline and at the time-point of relapse
           detection.

        5. To determine the rate of stage I seminoma and non-seminoma patients undergoing active
           surveillance.

        6. To obtain an overview of treatment and follow-up strategies in germ cell cancer patients
           in Switzerland.

           Outcome:

        7. To collect data on treatment sequelae following testicular cancer treatment in terms of
           organ function, cardiovascular risk factors, sexual health and socioeconomic aspects.

        8. To determine the rate of intermediate and poor-prognosis disease at relapse.

        9. To determine the rate of offspring spontaneously conceived after testicular cancer
           treatment.

      Design

      Prospective cohort study

      Centres All urologists, radiooncologists and oncologists are motivated to enrol their
      patients. We will aim at enrolling the majority of patients treated and followed in private
      practice.

      Patients Consecutive patients with testicular cancer of any type and any stage (incident
      cases). Testicular cancers are generally classified as seminomatous (seminoma) and
      nonseminomatous germ cell tumours (non-seminoma) of the testis. Mixed germ cell tumours
      belong to the group of non-seminomas. The stage of disease and the choice of treatment
      (active surveillance vs. chemotherapy vs. radiotherapy) define the risk of relapse, the
      pattern of relapse and the long-term toxicities. Staging in testicular cancer is performed
      according to the American Joint Committee on Cancer (AJCC) primary tumor, regional nodes,
      metastasis (TNM) staging system for testis cancer. Metastatic testicular cancers are
      classified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) risk
      groups.

      Clinical outcome

      Relapse of testicular cancer will be defined as rising concentrations of serum
      alphafetoprotein (AFP) above the upper limit of normal (typically > 13 μg/l) and/or human
      chorionic gonadotropin (HCG) above the upper limit of normal (typically > 5 U/l) and/or
      lactate dehydrogenase (LDH) above the upper limit of normal and confirmation of this rise in
      a second test four weeks later and/or radiographic evidence of metastatic disease in typical
      locations, and/or the presence of active germ cell tumour established by biopsy, whatever
      comes first.

      Index tests

      The following tests will be performed (ordered according to their burden for patients and
      cost): symptom assessment, physical examination, tumour marker measurement, chest x-ray,
      abdominal ultrasound and CT scan of abdomen and pelvis.

      Procedures

      Follow-up will be performed according to the mandatory follow-up schedule by a physician who
      has substantial experience in the treatment and surveillance of patients with germ cell
      tumours. Follow-up comprises thorough assessment of medical history and patients' symptoms
      with a focus on pain, appetite, fatigue, sexual function and activities of daily living;
      physical examination includes lung auscultation, abdominal, axillary, supra- and
      infradiaphragmatic regional lymph nodes and testicular palpation; serum tumour marker
      measurement: AFP, HCG and LDH; chest x-ray and abdominal ultrasound or CT scan. Even though
      the role of LDH in the follow-up is debatable, due to limited sensitivity and specificity and
      a high rate of false-positive tests, it can contribute to identify relapse in a significant
      number of cases, as shown in a recent publication. All the laboratory and radiological tests
      are performed independently and results are not made available to the investigator prior to
      symptom assessment and physical examination. In addition we will ascertain cardiovascular
      risk factors (smoking status, lipid profile, bodymass index, fasting glucose etc.), renal
      function, testosterone level, follicle stimulating hormone (FSH) level, lutenizing hormone
      (LH) level, and socioeconomic characteristics (education, employment, partnership) in annual
      intervals.

      Statistics

      Sample size considerations

      There are approximately 400 newly diagnosed testicular cancer patients in Switzerland per
      year. In Germany the annual testicular cancer incidence is about 4000. We aim at including
      approximately 300 patients per year in Switzerland over a duration of 3 years, with a total
      number of 900 patients. We are also aiming at registration of 2000 patients per year in
      Germany. Looking at the Swiss cohort, with an estimated 15% rate of relapses over a follow-up
      duration of two years, this will yield approximately 135 cases with relapse. This number will
      yield satisfactory statistical precision. An assumed sensitivity of 50% and a specificity of
      95% for Beta-HCG, for example, to detect a relapse will yield a positive likelihood ratio
      (LR) of 10 and a negative likelihood ratio of 0.53. Corresponding 95% confidence intervals
      will be 42 to 58% for sensitivity, 93 to 97% for specificity, 7.0 to 14.2 for the positive
      likelihood ratio and 0.44 to 0.62 for the negative likelihood ratio. An assumed sensitivity
      of 37% and a specificity of 99% for CT scans, for example, to detect a relapse will yield a
      positive likelihood ratio of 37 and a negative likelihood ratio of 0.64. Corresponding 95%
      confidence intervals will be 29 to 45% for sensitivity, 98 to 100% for specificity, 17.7 to
      77.4 for the positive likelihood ratio and 0.56 to 0.72 for the negative likelihood ratio.

      Measures of diagnostic accuracy will be determined in relation to the occurrence and
      timepoint of diagnosis of a relapse as specified above. Tests that were positive within the
      previous 8 weeks of established diagnosis of relapse will be considered as true positives,
      tests that remained negative during this time period as false negatives. Conversely, tests
      that were positive before this time period will be considered as false positives, and tests
      that were negative before this period as true negatives. We will use a multi-level model with
      random effects at the level of patients and time-points to estimate sensitivities and
      specificities and likelihood ratios, with the data organised in long format, with each test
      outcome (positive or negative) at each time-point represented by one line in the dataset,
      determining for each time-point whether it is within the 8-week time-period previous to the
      time-point of established diagnosis of relapse. The model takes into account the correlation
      of multiple time-points and tests within patients. The positive LR indicates how much more
      likely it is to find a positive test in patients with a relapse (sensitivity) as compared
      with those without relapse (1-specificity). Conversely, the negative LR specifies how much
      less likely it is to find a negative test in patients with relapse (1-sensitivity) as
      compared to patients without (specificity). A test will be considered to provide clinically
      relevant power to rule in or out a relapse if the positive and negative LRs are above 5 or
      below 0.2, respectively. The test will be considered to have a strong power to rule in or out
      a relapse if LRs are above 10 or below 0.1, respectively.

      As measures of the clinical impact of the addition of more extensive tests, we will examine
      the net re-classification improvement and the integrated discrimination improvement. The net
      re-classification improvement through the addition of a more extensive test is defined as the
      improvement of the probability of the appropriate classification of patients according to
      relapse status (presence or absence of a relapse), which is afforded by the addition of the
      more extensive test. This corresponds to the sum of differences in proportions of individuals
      classified positive minus the proportion classified negative for individuals who develop
      events, and the proportion of individuals classified negative minus the proportion classified
      positive for individuals who do not develop events. The integrated discrimination improvement
      is defined as the improvement in average sensitivity afforded by the addition of the more
      extensive test minus the potential loss in specificity afforded by the addition of the more
      extensive test. All analyses will be done using Stata, Release 11 (Stata Corp LP, College
      Station, TX).
observational model: Cohort
time perspective: Prospective
measure: Mode of relapse detection
time frame: 8 years
description: Diagnostic performance and the clinical impact of a variety of tests, including conventional radiographs, computed tomographies (CT), abdominal ultrasound, serum tumour markers (AFP, beta-HCG and LDH) and clinical signs and symptoms aimed at early detection of relapse after curative therapy with documented complete remission.
measure: Rate of relapses detected on chest x-ray in seminoma patients
time frame: 8 years
measure: Rate of false positive abnormalities on CT scan
time frame: 8 years
measure: Rate of false positive tumour marker elevations not due to seminomatous or non-seminomatous germ cell tumour relapses but due to other reasons
time frame: 8 years
measure: Patient characteristics at baseline and at the time-point of relapse detection.
time frame: 8 years
measure: Rate of stage I seminoma and non-seminoma patients undergoing active surveillance.
time frame: 8 years
measure: Overview of treatment and follow-up strategies in germ cell cancer patients in Switzerland, Austria and Germany
time frame: 8 years
measure: Treatment sequelae following testicular cancer treatment in terms of organ function, cardiovascular risk factors, sexual health and socioeconomic aspects.
time frame: 8 years
measure: Rate of intermediate and poor-prognosis disease at relapse.
time frame: 8 years
measure: Rate of offspring spontaneously conceived after testicular cancer treatment.
time frame: 8 years
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christian Rothermundt, Dr. med.
role: Principal Investigator
affiliation: Cantonal Hospital of St. Gallen
facility: 
status: Recruiting
contact: 
investigator: 
country: Switzerland
url: http://www.sag-tccs.com/
description: Webpage with basic information on the cohort study and link to the electronic case report form (eCRF) portal
responsible party type: Sponsor-Investigator
investigator affiliation: Cantonal Hospital of St. Gallen
investigator full name: Dr. med. Christian Rothermundt
investigator title: PD Dr. med.
mesh term: Testicular Neoplasms