Original Study
Initial Management of Testicular Cancer: Practice Survey Among Urologists and Pathologists Jérôme Rigaud,1 Xavier Durand,2 Philippe Camparo,3 Christophe Avances,4 Stéphane Culine,5 Philippe Sebe,6 Aude Flechon,7 Thibaut Murez,8 Michel Soulie9, and the members of the Comittee of Cancerology of the Association of French Urology (CCAFU) Abstract We realize a declarative practices survey about the management of testicular cancer. A total of 31.8% of 289 urologists who returned the questionnaires, declared that they performed the minimum assessment required by guidelines. Clinical practice did not comply with guidelines, and ask the question of what measures can be taken to ensure better application. Introduction: The objective of this study was to conduct a declarative professional practices survey among urologists of the French Association of Urology (AFU) and French pathologists concerning their management of testicular cancer. Materials and Methods: A questionnaire was sent to all urologists, members of the AFU, and another questionnaire was sent to French pathologists, members of the International Academy of Pathology, French Division, in June 2010. A total of 289 urologists (29%) and 84 pathologists (19%) returned the questionnaires. Results: Fifty-seven percent of urologists declared that they performed fewer than 5 orchidectomies per year. Pathologists declared that they examined less than 5 orchidectomy specimens per year in 24% of cases. The laboratory work-up (only alpha fetoprotein [AFP], lactate dehydrogenase [LDH], and total human chorionic gonadotropin [hCG]) and the radiological workup (only testicular ultrasound and chest, abdomen, and pelvis computed tomography [CT] scan) were performed strictly according to guidelines in 15.9% and 65.7% of cases, respectively. A total of 31.8% of urologists declared that they performed the minimum assessment required by guidelines (AFP, LDH, total hCG, testicular ultrasound and chest, abdomen, and pelvis CT scan plus other examinations not recommended). Prognostic factors of stage I tumors, to define the indications for adjuvant therapy, were correctly declared in 7.3% of nonseminomatous germ cell tumors (vascular and/or lymphatic emboli) and in 13.8% of seminomas (tumor size >4 cm and rete testis invasion). Conclusion: This survey demonstrated that clinical practice did not comply with guidelines, which raises the question of the measures that can be taken to ensure better application of guidelines or how to develop expert centers for the management of these rare tumors. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2014 Elsevier Inc. All rights reserved. Keywords: Compliance, Guidelines, Orchidectomy, Seminoma, Testis
Introduction French epidemiological data derived from the Institut National de Veille Sanitaire, published in 2011 indicated an estimated incidence of 2324 new cases of testicular cancer and a mortality of 86 cases per year. Analysis of these data from 1980 to 2010 demonstrated a regularly increasing incidence, and the mortality has
gradually decreased and has remained stable over the past 10 years because of improvement of treatments and more rigorously defined management.1 Two studies conducted in France have demonstrated a certain discordance between clinical practice and compliance with guidelines in the management of testicular cancer. A first study analyzed
1
8
Service Service 3 Service 4 Service 5 Service 6 Service France 7 Service 2
d’Urologie, Hôpital Hôtel Dieu, Nantes, France d’Urologie, Hôpital Val de Grâce, Paris, France d’Anatomo-Pathologie, Amiens, France d’Urologie, Clinique Kennedy, Nîmes, France d’Oncologie, Hôpital Saint Louis, Paris, France d’Urologie, Groupe Hospitalier Diaconesses, Croix Saint Simon, d’Oncologie Médicale, centre Léon Bérard, Lyon, France
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2013.12.002
Service d’Urologie, Hôpital Lapeyronie, Montpellier, France Service d’Urologie, Hôpital de Rangueil, Toulouse, France
9
Submitted: Sep 5, 2013; Accepted: Dec 23, 2013 Address for correspondence: Jérôme Rigaud, MD, PhD, Clinique Urologique, CHU Hôtel Dieu, 1 place Alexis Ricordeau, 44000 Nantes, France Fax: 02-40-08-39-22; e-mail contact: [email protected]
Clinical Genitourinary Cancer Month 2014
-1
Management of Testicular Cancer: Practice Survey the cancer registries of 11 centers comprising patients with testicular cancer during the period 2003-2004. The real management of these patients was compared with that defined in the 2002 French guidelines. The authors demonstrated that seminomas were managed according to guidelines in 44% of cases and nonseminomatous germ cell tumors (NSGCTs) were managed according to guidelines in 28% of cases by either a urologist, oncologist, or radiotherapist.2 Similarly, in a study from the Institut Gustave Roussy, the charts of 78 patients referred to this center for second-line chemotherapy between 2000 and 2010 were reviewed. The authors demonstrated that patients were initially managed, for first-line chemotherapy and surgery for residual masses, according to guidelines in 49% of cases. Major deviations were observed for chemotherapy dose and dose schedule and for the interval between the end of chemotherapy and surgery for residual masses.3 The objective of this study, conducted by the Comittee of Cancerology of the Association of French Urology - External Genital Organ subgroup, was to conduct a declarative survey on professional practices among urologists of the French Association of Urology (AFU) and pathologists of the International Academy of Pathology, French Division, concerning their management of testicular cancer.
Population A total of 289 urologists answered the questionnaire (52% private urologists, 37% hospital and/or university urologists, and 11% working in another health care structure). The percentage of urologist responders was 29% (289/997). A total of 84 pathologists answered the questionnaire (42% private pathologists, 43% hospital and/or university pathologists, and 15% other pathologists). For the pathologists, the percentage of responders was according to number of institutions because pathologists were specialized at each institution. The percentage of pathologist responders according to institution was 19% (84/450).
Results Incidence Urologists predominantly (57%) reported performing less than 5 orchidectomies for cancer per year and only 6% reported more than 10 orchidectomies per year (Fig. 1). Pathologists reported examining less than 5 orchidectomy specimens per year in 24% of cases, between 5 and 10 specimens in 43% of cases, and more than 10 specimens in 33% of cases.
Semen Samples
Materials and Methods Questionnaires All 997 urologist members of the French Association of Urology were invited, in June 2010, by e-mail via the Urofrance Web site to answer a multiple choice questionnaire on their practice and management of testicular cancer. No reminder e-mail was sent to increase the response rate. A second multiple choice questionnaire was sent by letter to 1200 pathologists at their workplace at 450 different institutions of the International Academy of Pathology, French Division, in June 2009 to study the frequency and modalities of examination of germ cell tumor orchidectomy specimens. No reminder letter was sent to increase the response rate.
Urologists reported systematically performing semen cryopreservation before the surgery in 62% of cases, often (> 40% of cases) in 17% of cases, not at all in 9% of cases, and only when requested by the patient in 12% of cases.
Serum Tumor Markers All urologists reported that they systematically performed a serum tumor marker analysis before the orchidectomy procedure. Figure 2 shows the frequency of biomarkers assayed. Tumor markers recommended by the AFU or European Association of Urology (EAU) include alpha fetoprotein (AFP), lactate dehydrogenase (LDH), and total human chorionic gonadotropin (hCG) (assay of the b subunit of hCG is not indicated).
Figure 1 Annual Frequency of Orchidectomy Performed by Urologists
2
-
Clinical Genitourinary Cancer Month 2014
Jérôme Rigaud et al Figure 2 Frequency of Biomarker Assays on the Laboratory Work-Up
Abbreviations: AFP ¼ alpha fetoprotein; hCG ¼ human chorionic gonadotropin; LDH ¼ lactate dehydrogenase.
Overall, 15.9% of urologists reported performing the tumor marker assessments according to guidelines (only AFP, LDH, and total hCG). Tumor marker staging comprising others markers in addition to the 3 markers recommended by guidelines (eg, beta hCG, carcinoembryonic antigen, estrogen, testosterone, etc) was performed by 45.7% of urologists (Fig. 3).
Radiological Staging Radiological staging was performed before the orchidectomy procedure in every case by 72% of urologists and often (> 40%
of cases) by 18% of urologists. Figure 4 shows the frequency of examinations requested preoperatively and/or postoperatively. The radiological staging recommended by the AFU or EAU includes testicular ultrasound and abdomen and pelvis computed tomography (CT) scan together with either chest x-ray or chest CT scan depending on the case. Overall, 65.7% of urologists reported performing the radiological staging according to guidelines (testicular ultrasound, chest, and abdomen and pelvis CT scan). A radiological staging comprising other examinations in addition to those recommended by guidelines (eg, positron emission tomography [PET]-CT scan, abdominal or
Figure 3 Frequency of Laboratory Work-Up Complying With Guidelines (AFP, LDH, and Total hCG)
Abbreviations: AFP ¼ alpha fetoprotein; hCG ¼ human chorionic gonadotropin; LDH ¼ lactate dehydrogenase.
Clinical Genitourinary Cancer Month 2014
-3
Management of Testicular Cancer: Practice Survey Figure 4 Frequency of Examinations Performed As Part of the Radiological Work-Up
Abbreviations: CT ¼ computed tomography; PET ¼ positron emission tomography.
scrotal magnetic resonance imaging [MRI], etc) was performed by 70.6% of urologists.
Background Information for the Pathology Examination The 2 questionnaires intended for urologists and pathologists both comprised questions concerning the information provided with the operative specimen. Figure 5 shows the discordance observed between the clinical, laboratory, and radiological information that the urologist declared to have indicated on the pathology examination request form and the presence of this information on the pathology examination request form received by the pathologist.
Assessment Before the Multidisciplinary Consultation Meeting Analysis of the mandatory biological and radiological staging required by guidelines declared by urologists before the multidisciplinary consultation meeting is represented in Figure 6. In practice, 31.8% of urologists reported that they performed at least a sufficient staging (AFP, LDH, total hCG, testicular ultrasound and chest, abdomen and pelvis CT and other nonrecommended examinations) to have complete charts before discussing the case in the multidisciplinary consultation meeting.
Figure 5 Presence of Clinical, Laboratory, and Radiological Data on the Pathology Request Form. Shown are the Urologist’s Point of View and the Pathologist’s Point of View
4
-
Clinical Genitourinary Cancer Month 2014
Jérôme Rigaud et al Figure 6 Frequency of Laboratory and Radiological Work-Up Complying With Guidelines. Laboratory Work-Up Included AFP, LDH, and Total hCG, and Radiological Work-Up Included Testicular Ultrasound and Chest, Abdomen, and Pelvis CT Scan
Abbreviations: AFP ¼ alpha fetoprotein; CT ¼ computed tomography; hCG ¼ human chorionic gonadotropin; LDH ¼ lactate dehydrogenase.
Stage 1 Seminoma
Stage 1 NSGCT
Figure 7 represents the urologists’ frequency of declaration of prognostic factors for stage I seminoma. The only 2 prognostic factors recognized by guidelines are tumor size > 4 cm and rete testis invasion. Only 13.8% of urologists exclusively declared these 2 prognostic factors. The preferred treatment proposal for stage I seminoma declared by urologists was: watchful waiting in 39% of cases, radiotherapy in 42% of cases, chemotherapy in 18% of cases (with bleomycin, etoposide, cisplatin (BEP) in 6% of cases and carboplatin in 12% of cases) and discussion with the patient in 2% of cases.
Figure 8 represents the urologists’ frequency of declaration of prognostic factors for stage 1 Non-Seminomatous Germ Cell Tumor (NSGCT). According to guidelines, the only validated prognostic factor is the presence of vascular and/or lymphatic emboli. Only 7.3% of urologists exclusively declared this prognostic factor. The preferred treatment proposal for stage 1 NSGCT declared by urologists was: watchful waiting in 42% of cases, retroperitoneal lymph node dissection in 6% of cases, radiotherapy in 1% of cases, and chemotherapy in 48% of cases (BEP in 42% of cases and carboplatin in 6% of cases), and discussion with the patient in 2% of cases.
Figure 7 Prognostic Factors for Stage I Seminoma
Clinical Genitourinary Cancer Month 2014
-5
Management of Testicular Cancer: Practice Survey Figure 8 Prognostic Factors for Stage I Nonseminomatous Germ Cell Tumor
Partial Orchidectomy
Discussion
Of the 289 urologists who returned the questionnaire, 79 (27%) reported that they performed partial orchidectomy. This type of surgery was performed only once a year by 77% of these urologists. The main indication for partial orchidectomy was suspicion of a benign tumor or asynchronous or metachronous bilateral tumors (Fig. 9). A large percentage (79.7%) of urologists reported that they never cooled the testis with ice during partial orchidectomy, 72.4% of urologists reported that they never or only rarely (less than 40% of cases) performed follow-up ultrasound examination, and 53.3% of urologists reported that they always or usually (more than 40% of cases) performed a biopsy in a zone of healthy tissue.
Testicular cancer is an uncommon cancer, but its incidence is regularly increasing with a low mortality, but has remained stable over recent years. Improvement of mortality is probably related to improvement of treatment. Management guidelines for testicular cancer have been clearly defined by various learned societies (AFU and EAU).4,5 There are very few discordances between the various guidelines allowing simple and consensual application of these guidelines in clinical practice. However, various studies have demonstrated a certain discordance between guidelines and the management actually performed in clinical practice. The clinical practice guidelines of these societies (AFU and EAU) comprise a biological staging: AFP, LDH, and total hCG (assay of
Figure 9 Indication for Partial Orchidectomy
6
-
Clinical Genitourinary Cancer Month 2014
Jérôme Rigaud et al the b subunit of hCG is not indicated); and a radiological staging: testicular ultrasound and abdomen and pelvis CT scan associated with either chest x-ray or chest CT scan depending on the case. Analysis of data concerning the management of testicular cancer reported by urologists in this study indicated major discrepancies with guidelines, because urologists reported that they performed a biological staging strictly according to guidelines in 15.9% of cases and a radiological staging strictly according to guidelines in 65.7% of cases. By extending these criteria to the recommendation of guidelines plus other investigations not recommended by guidelines, the minimum laboratory staging was performed in 45.7% of cases and the minimum radiological staging was performed in 70.6% of cases. In practice, only 31.8% of urologists reported performing the minimum staging required by guidelines (AFP, LDH, total hCG, testicular ultrasound, and chest, abdomen and pelvis CT, and other nonrecommended examinations) to ensure a complete assessment before presenting the case in a multidisciplinary consultation meeting. We also observed that in approximately 15%, a PET-CT scan or testicular MRI were reported without any indication for the initial staging. This point was important, representing an unnecessary cost with no effect on treatment. Histoprognostic factors necessary to determine the indication for adjuvant therapy for stage I tumors were correctly reported in 7.3% of NSGCT (vascular and/or lymphatic emboli) and 13.8% of seminomas (tumor size > 4 cm and rete testis invasion). In fact, only a small percentage of cases could be discussed with the good information regarding staging (biological and radiological) and with good histoprognostic factors. However, this information is very important to discuss the adjuvant treatment in stage I, with the patient who must be actively involved in the decision, and not only in 2% as reported by urologists. To our knowledge, no published study has compared the degree of compliance of clinical practice with society guidelines. Our study is therefore the first to quantify the differences between guidelines and clinical practice concerning the initial management of germ cell tumors of the testis. A Portuguese study retrospectively analyzed the quality of management of germ cell tumors between 1999 and 2000 in a series of 87 patients, including 79 cases of testicular cancer. With a median follow-up of 89 months, the authors observed an overall survival of 80% (100% for stage I, 92% for stage II, and 53% for stage III). These results were poorer than those of neighboring European countries, except for Spain, where similar results are also reported. The various hypotheses proposed to explain these results were delayed diagnosis, a high proportion of advanced stages, and large tumors and poor compliance with clinical management guidelines. These authors also showed overtreatment in 33% of patients and undertreatment in 5% of patients.6 The effect of poor application of guidelines on survival is difficult to assess, particularly for localized tumors, which usually have an excellent prognosis. In 2010, the Belgian Health Care Knowledge Centre published a report on quality indicators in oncology: testis cancer. The conclusions of this report were that primary data analysis showed a mixed picture of quality of care for patients with testicular cancer.
Although overall survival was good, certain elements indicated overuse or underuse of certain interventions. Similarly, an absence of risk adjustment (particularly for outcome indicators) in this report did not allow a reliable comparison between centers. Nevertheless, the preliminary analysis suggested considerable variability in the quality of care between centers and emphasized the importance of quality indicators and subsequent actions designed to improve these indicators, even for rare cancers like testicular cancer. The conclusion of the report was that: “Fragmentation of care and the small number of patients with testicular cancer treated each year in many centers raise questions concerning the organization of care for these patients and the need to centralize management of this disease in a limited number of centers.”7 These conclusions were similar to those of the study by Arvold et al, who demonstrated better survival and quality of life in patients managed in centers that treated a large number of testicular cancer patients compared with centers that treated a small number of patients, because centers with more limited experience more systematically administered adjuvant radiotherapy for stage I seminomas because of ignorance of the long-term toxicity of this treatment, but with no real effect on survival.8
Conclusion This declarative survey conducted among French urologists demonstrated failure to comply with clinical practice guidelines concerning the staging to be performed as part of the initial diagnostic assessment, because only 31.8% of urologists performed this staging at least according to guidelines (AFP, LDH, total hCG, testicular ultrasound, and chest, abdomen and pelvis CT scan). Similarly, less than 15% of urologists were familiar with the prognostic factors used to determine the indications for adjuvant therapy of stage I tumors. With various studies demonstrating the importance of appropriate therapeutic management, the findings of this survey raise 2 main questions: how can we ensure that guidelines are more rigorously applied? Should testicular tumors be treated exclusively in referral centers or expert centers able to apply the appropriate guidelines to ensure optimal management, resulting in better survival, and quality of life for patients?
Clinical Practice Points Testicular cancer is an uncommon cancer, but its incidence is
regularly increasing with a low mortality, but which has remained stable over recent years. Management guidelines for testicular cancer have been clearly defined by various learned societies. Improvement of mortality is probably related to improvement of treatment and the quality of guidelines. Several studies have demonstrated discordances between clinical practice and compliance with guidelines in the management of testicular cancer. The impact of poor application of guidelines on survival is difficult to assess, particularly for localized tumours which usually have an excellent prognosis. However some studies demonstrated better survival, quality of life and importance of quality indicators in patients managed in centres treating a large number of testicular cancer patients compared to centres treating a small number of patients.
Clinical Genitourinary Cancer Month 2014
-7
Management of Testicular Cancer: Practice Survey Our study quantified the differences between guidelines and
References
clinical practice concerning the initial management of germ cell tumours of the testis. In fact only a few percentages of cases could be discussed with the good informations of staging (biological and radiological) and with the good histoprognostic factors. The findings of this survey raise two main questions: How can we ensure that guidelines are more rigorously applied? Should testicular tumours be treated exclusively in referral centres or expert centres able to apply the appropriate guidelines to ensure optimal management, resulting in better survival and quality of life for patients?
1. Kudjawu Y, Uhry Z, Danzon A, Bloch J. Cancer du testicule: évolution nationale et variations régionales du taux de patients opérés, 1998-2008. Données hospitalières. Saint-Maurice: Institut de veille sanitaire; 2011. 2. Culine S, Hoppe S, Hennequin C, Saves M, Mottet N. FRANCIM network. Management of testicular neoplasms in France and compliance with national guidelines. J Clin Oncol 2010; 28: 15s (abstract 4580). 3. Thibault C, Loriot Y, Gonzales DB, et al. Relapses in metastatic germ-cell tumors and relationship to international guidelines compliance: a study from the Institut Gustave Roussy. J Clin Oncol 2012; 30: 5s (abstract 323). 4. Durand X, Rigaud J, Avances C, et al. Recommandations en Onco-Urologie 2010: Tumeurs germinales du testicule. Progrès en Urologie 2010; 20:S297-309. 5. Albers P, Albrecht W, Algaba F, et al. EAU guidelines on testicular cancer: 2011 update. Eur Urol 2011; 60:304-19. 6. Passos-Coelho JL, Castro Ribeiro M, Santos E, Sousa Pontes C, Brito B, Miranda AC. Suboptimal survival of male germ-cell tumors in southern Portugalea population-based retrospective study for cases diagnosed in 1999 and 2000. Ann Oncol 2011; 22:1215-20. 7. Vlayen J, Vrijens F, Beirens K, Stordeur S, Devriese S, Van Eycken E. Indicateurs de qualité en oncologie: cancer du testicule. Good Clinical Practice (GCP). Bruxelles: Centre fédéral d’expertise des soins de santé (KCE). 2010; KCE Reports 149B. D2010/10.273/97. 8. Arvold ND, Catalano PJ, Sweeney CJ, et al. Barriers to the implementation of surveillance for stage I testicular seminoma. Int J Radiat Oncol Biol Phys 2012; 84:383-9.
Disclosure The authors have stated that they have no conflicts of interest.
8
-
Clinical Genitourinary Cancer Month 2014
Initial Management of Testicular Cancer: Practice Survey Among Urologists and Pathologists Jérôme Rigaud,1 Xavier Durand,2 Philippe Camparo,3 Christophe Avances,4 Stéphane Culine,5 Philippe Sebe,6 Aude Flechon,7 Thibaut Murez,8 Michel Soulie9, and the members of the Comittee of Cancerology of the Association of French Urology (CCAFU) Abstract We realize a declarative practices survey about the management of testicular cancer. A total of 31.8% of 289 urologists who returned the questionnaires, declared that they performed the minimum assessment required by guidelines. Clinical practice did not comply with guidelines, and ask the question of what measures can be taken to ensure better application. Introduction: The objective of this study was to conduct a declarative professional practices survey among urologists of the French Association of Urology (AFU) and French pathologists concerning their management of testicular cancer. Materials and Methods: A questionnaire was sent to all urologists, members of the AFU, and another questionnaire was sent to French pathologists, members of the International Academy of Pathology, French Division, in June 2010. A total of 289 urologists (29%) and 84 pathologists (19%) returned the questionnaires. Results: Fifty-seven percent of urologists declared that they performed fewer than 5 orchidectomies per year. Pathologists declared that they examined less than 5 orchidectomy specimens per year in 24% of cases. The laboratory work-up (only alpha fetoprotein [AFP], lactate dehydrogenase [LDH], and total human chorionic gonadotropin [hCG]) and the radiological workup (only testicular ultrasound and chest, abdomen, and pelvis computed tomography [CT] scan) were performed strictly according to guidelines in 15.9% and 65.7% of cases, respectively. A total of 31.8% of urologists declared that they performed the minimum assessment required by guidelines (AFP, LDH, total hCG, testicular ultrasound and chest, abdomen, and pelvis CT scan plus other examinations not recommended). Prognostic factors of stage I tumors, to define the indications for adjuvant therapy, were correctly declared in 7.3% of nonseminomatous germ cell tumors (vascular and/or lymphatic emboli) and in 13.8% of seminomas (tumor size >4 cm and rete testis invasion). Conclusion: This survey demonstrated that clinical practice did not comply with guidelines, which raises the question of the measures that can be taken to ensure better application of guidelines or how to develop expert centers for the management of these rare tumors. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2014 Elsevier Inc. All rights reserved. Keywords: Compliance, Guidelines, Orchidectomy, Seminoma, Testis
Introduction French epidemiological data derived from the Institut National de Veille Sanitaire, published in 2011 indicated an estimated incidence of 2324 new cases of testicular cancer and a mortality of 86 cases per year. Analysis of these data from 1980 to 2010 demonstrated a regularly increasing incidence, and the mortality has
gradually decreased and has remained stable over the past 10 years because of improvement of treatments and more rigorously defined management.1 Two studies conducted in France have demonstrated a certain discordance between clinical practice and compliance with guidelines in the management of testicular cancer. A first study analyzed
1
8
Service Service 3 Service 4 Service 5 Service 6 Service France 7 Service 2
d’Urologie, Hôpital Hôtel Dieu, Nantes, France d’Urologie, Hôpital Val de Grâce, Paris, France d’Anatomo-Pathologie, Amiens, France d’Urologie, Clinique Kennedy, Nîmes, France d’Oncologie, Hôpital Saint Louis, Paris, France d’Urologie, Groupe Hospitalier Diaconesses, Croix Saint Simon, d’Oncologie Médicale, centre Léon Bérard, Lyon, France
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2013.12.002
Service d’Urologie, Hôpital Lapeyronie, Montpellier, France Service d’Urologie, Hôpital de Rangueil, Toulouse, France
9
Submitted: Sep 5, 2013; Accepted: Dec 23, 2013 Address for correspondence: Jérôme Rigaud, MD, PhD, Clinique Urologique, CHU Hôtel Dieu, 1 place Alexis Ricordeau, 44000 Nantes, France Fax: 02-40-08-39-22; e-mail contact: [email protected]
Clinical Genitourinary Cancer Month 2014
-1
Management of Testicular Cancer: Practice Survey the cancer registries of 11 centers comprising patients with testicular cancer during the period 2003-2004. The real management of these patients was compared with that defined in the 2002 French guidelines. The authors demonstrated that seminomas were managed according to guidelines in 44% of cases and nonseminomatous germ cell tumors (NSGCTs) were managed according to guidelines in 28% of cases by either a urologist, oncologist, or radiotherapist.2 Similarly, in a study from the Institut Gustave Roussy, the charts of 78 patients referred to this center for second-line chemotherapy between 2000 and 2010 were reviewed. The authors demonstrated that patients were initially managed, for first-line chemotherapy and surgery for residual masses, according to guidelines in 49% of cases. Major deviations were observed for chemotherapy dose and dose schedule and for the interval between the end of chemotherapy and surgery for residual masses.3 The objective of this study, conducted by the Comittee of Cancerology of the Association of French Urology - External Genital Organ subgroup, was to conduct a declarative survey on professional practices among urologists of the French Association of Urology (AFU) and pathologists of the International Academy of Pathology, French Division, concerning their management of testicular cancer.
Population A total of 289 urologists answered the questionnaire (52% private urologists, 37% hospital and/or university urologists, and 11% working in another health care structure). The percentage of urologist responders was 29% (289/997). A total of 84 pathologists answered the questionnaire (42% private pathologists, 43% hospital and/or university pathologists, and 15% other pathologists). For the pathologists, the percentage of responders was according to number of institutions because pathologists were specialized at each institution. The percentage of pathologist responders according to institution was 19% (84/450).
Results Incidence Urologists predominantly (57%) reported performing less than 5 orchidectomies for cancer per year and only 6% reported more than 10 orchidectomies per year (Fig. 1). Pathologists reported examining less than 5 orchidectomy specimens per year in 24% of cases, between 5 and 10 specimens in 43% of cases, and more than 10 specimens in 33% of cases.
Semen Samples
Materials and Methods Questionnaires All 997 urologist members of the French Association of Urology were invited, in June 2010, by e-mail via the Urofrance Web site to answer a multiple choice questionnaire on their practice and management of testicular cancer. No reminder e-mail was sent to increase the response rate. A second multiple choice questionnaire was sent by letter to 1200 pathologists at their workplace at 450 different institutions of the International Academy of Pathology, French Division, in June 2009 to study the frequency and modalities of examination of germ cell tumor orchidectomy specimens. No reminder letter was sent to increase the response rate.
Urologists reported systematically performing semen cryopreservation before the surgery in 62% of cases, often (> 40% of cases) in 17% of cases, not at all in 9% of cases, and only when requested by the patient in 12% of cases.
Serum Tumor Markers All urologists reported that they systematically performed a serum tumor marker analysis before the orchidectomy procedure. Figure 2 shows the frequency of biomarkers assayed. Tumor markers recommended by the AFU or European Association of Urology (EAU) include alpha fetoprotein (AFP), lactate dehydrogenase (LDH), and total human chorionic gonadotropin (hCG) (assay of the b subunit of hCG is not indicated).
Figure 1 Annual Frequency of Orchidectomy Performed by Urologists
2
-
Clinical Genitourinary Cancer Month 2014
Jérôme Rigaud et al Figure 2 Frequency of Biomarker Assays on the Laboratory Work-Up
Abbreviations: AFP ¼ alpha fetoprotein; hCG ¼ human chorionic gonadotropin; LDH ¼ lactate dehydrogenase.
Overall, 15.9% of urologists reported performing the tumor marker assessments according to guidelines (only AFP, LDH, and total hCG). Tumor marker staging comprising others markers in addition to the 3 markers recommended by guidelines (eg, beta hCG, carcinoembryonic antigen, estrogen, testosterone, etc) was performed by 45.7% of urologists (Fig. 3).
Radiological Staging Radiological staging was performed before the orchidectomy procedure in every case by 72% of urologists and often (> 40%
of cases) by 18% of urologists. Figure 4 shows the frequency of examinations requested preoperatively and/or postoperatively. The radiological staging recommended by the AFU or EAU includes testicular ultrasound and abdomen and pelvis computed tomography (CT) scan together with either chest x-ray or chest CT scan depending on the case. Overall, 65.7% of urologists reported performing the radiological staging according to guidelines (testicular ultrasound, chest, and abdomen and pelvis CT scan). A radiological staging comprising other examinations in addition to those recommended by guidelines (eg, positron emission tomography [PET]-CT scan, abdominal or
Figure 3 Frequency of Laboratory Work-Up Complying With Guidelines (AFP, LDH, and Total hCG)
Abbreviations: AFP ¼ alpha fetoprotein; hCG ¼ human chorionic gonadotropin; LDH ¼ lactate dehydrogenase.
Clinical Genitourinary Cancer Month 2014
-3
Management of Testicular Cancer: Practice Survey Figure 4 Frequency of Examinations Performed As Part of the Radiological Work-Up
Abbreviations: CT ¼ computed tomography; PET ¼ positron emission tomography.
scrotal magnetic resonance imaging [MRI], etc) was performed by 70.6% of urologists.
Background Information for the Pathology Examination The 2 questionnaires intended for urologists and pathologists both comprised questions concerning the information provided with the operative specimen. Figure 5 shows the discordance observed between the clinical, laboratory, and radiological information that the urologist declared to have indicated on the pathology examination request form and the presence of this information on the pathology examination request form received by the pathologist.
Assessment Before the Multidisciplinary Consultation Meeting Analysis of the mandatory biological and radiological staging required by guidelines declared by urologists before the multidisciplinary consultation meeting is represented in Figure 6. In practice, 31.8% of urologists reported that they performed at least a sufficient staging (AFP, LDH, total hCG, testicular ultrasound and chest, abdomen and pelvis CT and other nonrecommended examinations) to have complete charts before discussing the case in the multidisciplinary consultation meeting.
Figure 5 Presence of Clinical, Laboratory, and Radiological Data on the Pathology Request Form. Shown are the Urologist’s Point of View and the Pathologist’s Point of View
4
-
Clinical Genitourinary Cancer Month 2014
Jérôme Rigaud et al Figure 6 Frequency of Laboratory and Radiological Work-Up Complying With Guidelines. Laboratory Work-Up Included AFP, LDH, and Total hCG, and Radiological Work-Up Included Testicular Ultrasound and Chest, Abdomen, and Pelvis CT Scan
Abbreviations: AFP ¼ alpha fetoprotein; CT ¼ computed tomography; hCG ¼ human chorionic gonadotropin; LDH ¼ lactate dehydrogenase.
Stage 1 Seminoma
Stage 1 NSGCT
Figure 7 represents the urologists’ frequency of declaration of prognostic factors for stage I seminoma. The only 2 prognostic factors recognized by guidelines are tumor size > 4 cm and rete testis invasion. Only 13.8% of urologists exclusively declared these 2 prognostic factors. The preferred treatment proposal for stage I seminoma declared by urologists was: watchful waiting in 39% of cases, radiotherapy in 42% of cases, chemotherapy in 18% of cases (with bleomycin, etoposide, cisplatin (BEP) in 6% of cases and carboplatin in 12% of cases) and discussion with the patient in 2% of cases.
Figure 8 represents the urologists’ frequency of declaration of prognostic factors for stage 1 Non-Seminomatous Germ Cell Tumor (NSGCT). According to guidelines, the only validated prognostic factor is the presence of vascular and/or lymphatic emboli. Only 7.3% of urologists exclusively declared this prognostic factor. The preferred treatment proposal for stage 1 NSGCT declared by urologists was: watchful waiting in 42% of cases, retroperitoneal lymph node dissection in 6% of cases, radiotherapy in 1% of cases, and chemotherapy in 48% of cases (BEP in 42% of cases and carboplatin in 6% of cases), and discussion with the patient in 2% of cases.
Figure 7 Prognostic Factors for Stage I Seminoma
Clinical Genitourinary Cancer Month 2014
-5
Management of Testicular Cancer: Practice Survey Figure 8 Prognostic Factors for Stage I Nonseminomatous Germ Cell Tumor
Partial Orchidectomy
Discussion
Of the 289 urologists who returned the questionnaire, 79 (27%) reported that they performed partial orchidectomy. This type of surgery was performed only once a year by 77% of these urologists. The main indication for partial orchidectomy was suspicion of a benign tumor or asynchronous or metachronous bilateral tumors (Fig. 9). A large percentage (79.7%) of urologists reported that they never cooled the testis with ice during partial orchidectomy, 72.4% of urologists reported that they never or only rarely (less than 40% of cases) performed follow-up ultrasound examination, and 53.3% of urologists reported that they always or usually (more than 40% of cases) performed a biopsy in a zone of healthy tissue.
Testicular cancer is an uncommon cancer, but its incidence is regularly increasing with a low mortality, but has remained stable over recent years. Improvement of mortality is probably related to improvement of treatment. Management guidelines for testicular cancer have been clearly defined by various learned societies (AFU and EAU).4,5 There are very few discordances between the various guidelines allowing simple and consensual application of these guidelines in clinical practice. However, various studies have demonstrated a certain discordance between guidelines and the management actually performed in clinical practice. The clinical practice guidelines of these societies (AFU and EAU) comprise a biological staging: AFP, LDH, and total hCG (assay of
Figure 9 Indication for Partial Orchidectomy
6
-
Clinical Genitourinary Cancer Month 2014
Jérôme Rigaud et al the b subunit of hCG is not indicated); and a radiological staging: testicular ultrasound and abdomen and pelvis CT scan associated with either chest x-ray or chest CT scan depending on the case. Analysis of data concerning the management of testicular cancer reported by urologists in this study indicated major discrepancies with guidelines, because urologists reported that they performed a biological staging strictly according to guidelines in 15.9% of cases and a radiological staging strictly according to guidelines in 65.7% of cases. By extending these criteria to the recommendation of guidelines plus other investigations not recommended by guidelines, the minimum laboratory staging was performed in 45.7% of cases and the minimum radiological staging was performed in 70.6% of cases. In practice, only 31.8% of urologists reported performing the minimum staging required by guidelines (AFP, LDH, total hCG, testicular ultrasound, and chest, abdomen and pelvis CT, and other nonrecommended examinations) to ensure a complete assessment before presenting the case in a multidisciplinary consultation meeting. We also observed that in approximately 15%, a PET-CT scan or testicular MRI were reported without any indication for the initial staging. This point was important, representing an unnecessary cost with no effect on treatment. Histoprognostic factors necessary to determine the indication for adjuvant therapy for stage I tumors were correctly reported in 7.3% of NSGCT (vascular and/or lymphatic emboli) and 13.8% of seminomas (tumor size > 4 cm and rete testis invasion). In fact, only a small percentage of cases could be discussed with the good information regarding staging (biological and radiological) and with good histoprognostic factors. However, this information is very important to discuss the adjuvant treatment in stage I, with the patient who must be actively involved in the decision, and not only in 2% as reported by urologists. To our knowledge, no published study has compared the degree of compliance of clinical practice with society guidelines. Our study is therefore the first to quantify the differences between guidelines and clinical practice concerning the initial management of germ cell tumors of the testis. A Portuguese study retrospectively analyzed the quality of management of germ cell tumors between 1999 and 2000 in a series of 87 patients, including 79 cases of testicular cancer. With a median follow-up of 89 months, the authors observed an overall survival of 80% (100% for stage I, 92% for stage II, and 53% for stage III). These results were poorer than those of neighboring European countries, except for Spain, where similar results are also reported. The various hypotheses proposed to explain these results were delayed diagnosis, a high proportion of advanced stages, and large tumors and poor compliance with clinical management guidelines. These authors also showed overtreatment in 33% of patients and undertreatment in 5% of patients.6 The effect of poor application of guidelines on survival is difficult to assess, particularly for localized tumors, which usually have an excellent prognosis. In 2010, the Belgian Health Care Knowledge Centre published a report on quality indicators in oncology: testis cancer. The conclusions of this report were that primary data analysis showed a mixed picture of quality of care for patients with testicular cancer.
Although overall survival was good, certain elements indicated overuse or underuse of certain interventions. Similarly, an absence of risk adjustment (particularly for outcome indicators) in this report did not allow a reliable comparison between centers. Nevertheless, the preliminary analysis suggested considerable variability in the quality of care between centers and emphasized the importance of quality indicators and subsequent actions designed to improve these indicators, even for rare cancers like testicular cancer. The conclusion of the report was that: “Fragmentation of care and the small number of patients with testicular cancer treated each year in many centers raise questions concerning the organization of care for these patients and the need to centralize management of this disease in a limited number of centers.”7 These conclusions were similar to those of the study by Arvold et al, who demonstrated better survival and quality of life in patients managed in centers that treated a large number of testicular cancer patients compared with centers that treated a small number of patients, because centers with more limited experience more systematically administered adjuvant radiotherapy for stage I seminomas because of ignorance of the long-term toxicity of this treatment, but with no real effect on survival.8
Conclusion This declarative survey conducted among French urologists demonstrated failure to comply with clinical practice guidelines concerning the staging to be performed as part of the initial diagnostic assessment, because only 31.8% of urologists performed this staging at least according to guidelines (AFP, LDH, total hCG, testicular ultrasound, and chest, abdomen and pelvis CT scan). Similarly, less than 15% of urologists were familiar with the prognostic factors used to determine the indications for adjuvant therapy of stage I tumors. With various studies demonstrating the importance of appropriate therapeutic management, the findings of this survey raise 2 main questions: how can we ensure that guidelines are more rigorously applied? Should testicular tumors be treated exclusively in referral centers or expert centers able to apply the appropriate guidelines to ensure optimal management, resulting in better survival, and quality of life for patients?
Clinical Practice Points Testicular cancer is an uncommon cancer, but its incidence is
regularly increasing with a low mortality, but which has remained stable over recent years. Management guidelines for testicular cancer have been clearly defined by various learned societies. Improvement of mortality is probably related to improvement of treatment and the quality of guidelines. Several studies have demonstrated discordances between clinical practice and compliance with guidelines in the management of testicular cancer. The impact of poor application of guidelines on survival is difficult to assess, particularly for localized tumours which usually have an excellent prognosis. However some studies demonstrated better survival, quality of life and importance of quality indicators in patients managed in centres treating a large number of testicular cancer patients compared to centres treating a small number of patients.
Clinical Genitourinary Cancer Month 2014
-7
Management of Testicular Cancer: Practice Survey Our study quantified the differences between guidelines and
References
clinical practice concerning the initial management of germ cell tumours of the testis. In fact only a few percentages of cases could be discussed with the good informations of staging (biological and radiological) and with the good histoprognostic factors. The findings of this survey raise two main questions: How can we ensure that guidelines are more rigorously applied? Should testicular tumours be treated exclusively in referral centres or expert centres able to apply the appropriate guidelines to ensure optimal management, resulting in better survival and quality of life for patients?
1. Kudjawu Y, Uhry Z, Danzon A, Bloch J. Cancer du testicule: évolution nationale et variations régionales du taux de patients opérés, 1998-2008. Données hospitalières. Saint-Maurice: Institut de veille sanitaire; 2011. 2. Culine S, Hoppe S, Hennequin C, Saves M, Mottet N. FRANCIM network. Management of testicular neoplasms in France and compliance with national guidelines. J Clin Oncol 2010; 28: 15s (abstract 4580). 3. Thibault C, Loriot Y, Gonzales DB, et al. Relapses in metastatic germ-cell tumors and relationship to international guidelines compliance: a study from the Institut Gustave Roussy. J Clin Oncol 2012; 30: 5s (abstract 323). 4. Durand X, Rigaud J, Avances C, et al. Recommandations en Onco-Urologie 2010: Tumeurs germinales du testicule. Progrès en Urologie 2010; 20:S297-309. 5. Albers P, Albrecht W, Algaba F, et al. EAU guidelines on testicular cancer: 2011 update. Eur Urol 2011; 60:304-19. 6. Passos-Coelho JL, Castro Ribeiro M, Santos E, Sousa Pontes C, Brito B, Miranda AC. Suboptimal survival of male germ-cell tumors in southern Portugalea population-based retrospective study for cases diagnosed in 1999 and 2000. Ann Oncol 2011; 22:1215-20. 7. Vlayen J, Vrijens F, Beirens K, Stordeur S, Devriese S, Van Eycken E. Indicateurs de qualité en oncologie: cancer du testicule. Good Clinical Practice (GCP). Bruxelles: Centre fédéral d’expertise des soins de santé (KCE). 2010; KCE Reports 149B. D2010/10.273/97. 8. Arvold ND, Catalano PJ, Sweeney CJ, et al. Barriers to the implementation of surveillance for stage I testicular seminoma. Int J Radiat Oncol Biol Phys 2012; 84:383-9.
Disclosure The authors have stated that they have no conflicts of interest.
8
-
Clinical Genitourinary Cancer Month 2014
