Cancer and Reproducibility of Decisions

Cancer and Reproducibility of DecisionsUrologic pubic louse What about duplicability of conclusion made at multidisciplinary team management?BAYOUD Y, LOOCK PY, MENARD J, MESSAOUDI R, RIPERT T, PIERREVELCIN J, KOZAL S, LEON P, KAMDOUM M, CHOLET I, LARRE S . get upIntroduction The prostate cancer (PCa) interference is multimodal. Thus multidisciplinary team management (MDTM) termination- do process appears as a tool to answer all aspects of PCa. To evaluate the duplicability of therapeutic decisions made at MDTM.Materials and Methods We comp ared therapeutic decisions of PCa by presenting the homogeneous file of patient under a fake identity after 6 to 12 months from the commencement ceremony presentation. Forty-nine files of extreme prostatectomy (RP) (28 pT2, 21 pT3) performed for clinical localized PCa were compensateed at MDTM which included urologist, oncologist, pathologist and radiologist. Analysis of therapeutic decisions comprised criteria as TNM stage, Gleason scor e, margin posture and comorbidities. The duplicability was assessed statistically by Kappa coefficient.Results Forty-nine file of radical prostatectomy (RP). The mean age was similar in both groups. The mean PSA was 8,32 ng/ ml (3,56-19,5) in pT2 group and 9.4ng/ml (3,8-22) in pT3 group. The margin status was incontrovertible in 25% and 47,6% respectively in pT2 and pT3 group. Decision made for pT2 group were the like in 100% case (k=1). In the group of pT3 (n=21), 33% of decision were different at second MDTM, especially for pT3b with only 29% logical decision (k= 0,1). Concerning pT3a, 86% of decision were reproducible (k= 0,74).Conclusion We showed a reliability and duplicability of decision made at MDTM when guidelines are well defined. The therapeutic attitudes were less reproducible in locally advanced PCa but decision concerning those cases should be made in the setting of guidelines.Key words Cancer, Kappa coefficient, Prostate, multidisciplinary, Reproducibility.INTRODU CTIONThe prostate cancer (PCa) is the nigh frequent cancer in men as well in Europe and USA (1). The PCa counts for 11% of all men cancers and its responsible for 9% of the mortality by cancer in men in Europe. In France in 2010, the incidence of PCa was 71577 cases and the related mortality of PCa at the same year was 8791 deaths which represent a 2.5% less mortality per year during last years (2).The multidisciplinary team management becomes an obligation for all oncologic fields as mentioned by the cut government law cancer program 2003-2007, this program stipulate that each new patient should benefit from MDTM decision-making process, organize the setting of MDTM and as well as gives tools to develop examinations of investigate for a new diagnosis and therapeutic arsenal (3). Some urologists express some doubt about the interest of MDTM because of its a new weight without assigned budget while new(prenominal)s see in the MDTM an equality of chance of patients, and possibi lity to include patients in trials and protocols. Number of European think over showed the interest of MDTM and its full impact on survival (4, 5).The efficiency of decisions made at MDTM is obvious but the evidence about their reproducibility remains doubtful. Through patients underwent a radical prostatectomy (RP) for localized prostate cancer (PCa) and represented identically, we evaluated a reproducibility of decision made at MDTM.Materials and MethodsFrom January 2011 to March 2012, 183 patients underwent radical prostatectomy for localized PCa, all of them were presented at MDTM and decision of diagnosis and treatment validated. Within those patients some files were selected prospectively for a second presentation. All of patients were presented identically under a fake identity6 to 12 months later. for each one file contained a full filled form including all decision- making parameters concerning patient (appendix 1).Patients were selected after agreement of their urologis t who didnt participate at decision making process at a second presentation. We also presented a case of patient which can be susceptible for debate and distinguished two groups. firstly one with localized PCa with or without positive margins (pT2 R0 or R1) and second one with advanced PCa (pT3a or b, R0 or R1) regarding 2002 pTNM classification. Criteria of selection was to select patients with localized and advanced PCa, we also selected those at kickoff and high risk of local and systemic retroversion based on pTNM and gleason score, two only important parameters predicting local and systemic relapse after RP we had at this moment of decision making process (1). Thus we tried to have each half of group with gleason score at low and high risk of relapse. The group of pT2 comprised approximately 50% of patient with gleason score 6 and the group of pT3 comprised approximately 50% of patient with gleason score 3+4 (table 1). We compared a decision made for each patient in both M DTM. All decisions were made accordingly to usual criteria as pTNM stage, Gleason score, margin status, comorbidities and choice of patients.MDTM comprised 5 urologists seniors and 2 juniors, 1 pathologist, 1 medical oncologist, 1 radiotherapist and 1 radiologist and organized weekly.The statistical analysis chosen for comparison between first and second decision made at MDTM was Kappa coefficient which scale vary from non-agreement to perfect. The coefficient Kappa is a statistical tool to assess reproducibility. It also allows an estimate of concordance of qualitative judgments for the same situations by two different observers (6). We compared all criteria of study with t-test for independent samples using meansSD.ResultsFrom January 2011 to March 2012, 183 patients underwent RP for localized PCa. From this population forty nine patients were selected prospectively and distribution of patients was as follows 28 pT2c, 21 pT3 (14 pT3a and 7 pT3b). Baseline criteria of patient group and t-test are resumed in table 1.We observed a reproducibility of 100 % of the group of pT2c on an individual basis of the margin status and Gleason score. Kappa coefficient was perfect (=1). In the group of pT3a, decisions were reproducible in 86% cases, with therapeutic attitude putting in balance surveillance or extra beam radiation therapy (EBRT) (figure 1). The distribution of decisions was as follows 28% for EBRT, 72% for surveillance at MDTM 1 and 14% for EBRT, 86% for surveillance. The coefficient Kappa was substantial with a set of 0,74. In the group of pT3b, decisions were reproducible in only 29% cases. Therapeutic decisions were EBRT plus androgen deprivation therapy (ADT) in 71% patients and surveillance in 29% patients at MDTM 1, while therapeutic decisions at MDTM 2 were 14,5% for EBRT, 14,5% for EBRT plus androgen deprivation therapy and 71% for surveillance ( insert 2). The Kappa coefficient was slight with a value of 0,1.DiscussionOur study showed the pertinenc e of MDTM recommended by Law of cancer program 2003-2007 (3). Many European studies showed the interest of MDTM (4, 5), but number of urologists expresses some doubts about benefits, exposing as argument a new burden without assigned budget. This position is partly supported by Asher PL et al, they reported in 124 cases of urological cancer, MDTM changed therapeutic attitude in only 2% cases, therefrom authors suggested that urologist could presented only few patients to MDTM which reduced significantly a working cost without compromising therapeutic patients chance (7).Van Belle S showed that MDTM complete by the Belgian governmental program was a success thanks to specifically assigned budget. Authors reported also indirect evidence between MDTM and survival rate of cancer in Belgium because its within the five trump European rates (2,3 and (8)This hypothesis was sustained by results of Sternberg CN et al study, they leave offd of ripe effect of MDTM on free recurrence surviv al of PCa in patients at high risk of recurrence, in particular phase III of TAX 3501 where was compared treatment with immediate or differed ADT with or without docetaxel after RP (9).Our study showed reliability and reproducibility of decisions made at MDTM. This is valid in pT2 patients group in whom 100% of reproducibility was observed, while pT3a patients group showed 86% reproducibility ( = 0.74). However pT3b patients group showed worse rate of reproducibility with 29% ( = 0.1), this result should be interpreted with caution considering the pettiness of sample (n=7). Further studieswith biggest sample are mandatory to make conclusion. Those cases are still complex situations demanding MDTM decision-making process.The lack of well-defined recommendations certainly contributes to the weak rate of reproducibility of decision made at MDTM for locally advanced PCa. GETUG 17 trial which compares immediate EBRT associated to ADT versus deferred EBRT at biochemical recurrence with A DT for patients underwent RP in whom definitive pathology result is pT3 R1( R1 positive surgical margins) will contribute to clarify recommendations. The interest of MDTM is to include patients in the same trial.To support this idea, Nguyen TD et al showed in their study for breast cancer which recommendations are well designed that 92% of MDTM decisions were in accordance to recommendations and 96% of these decisions were followed by patients responsible doctor. They conclude also of the interest of including patients in trial (10). The same conclusions were reported by Carducci MA et al, they surveyed prospectively 8 cancers in 6 hospitals, and they showed that 128 patients of 153 (84%) benefited from specific therapeutic decisions thanks to MDTM. Authors insisted on the interest of MDTM in advanced PCa and inclusion body of patients in trial (11).Several studies seem to end on the interest of a tool to standardize and optimize the therapeutic decisions. Thus, Benjamin A et al r eported significant differences in care of localized PCa in the United States of America. Between 2000 and 2001, 2775 cases of localized PCa were collected from 55160 patients. They considered many criteria as geographic location, type of unveiling (academic hospital or community hospital), pathology analysis and revue after treatment. Significant differences were observed regarding geographic origin and type of institution where treatmentwas provided. Besides criteria as tumor volume, extra capsular extension and pTNM stage were considered for making decision process respectively only in 37,1%, 68,6%, 48,2% (11). Hardly 55% of patients benefited from a follow-up (12).Clarke MG et al showed in cohort of 30 urologists for whom were subjected questionnaires representing patients scenarios with prostate cancer, a mean of 3 cues from 9 were used to make therapeutic decision. Criteria as feel expectancy, digital rectal examination, age of patient and patients choice were rarely used. The authors also reported that urologists made a different therapeutic decision in 31,4% cases when they answered a same questionnaire at different time. They conclude that well defined recommendations and MDTM will standardize process of making decision and enhance reproducibility of decisions (13). These observations were also demonstrated by Wilson J et al in their study concerning 32 urologists from Great Britain, for whom 70 questionnaires representing medical history of prostate cancer were subjected. xiii questionnaires among 70 were repeated to evaluate intra- observer reproducibility. They reported that intra-observer reproducibility varied from 56% to 79%, while inter-observer reproducibility varied from 24% to 57%. Authors conclude on interest of standardizing therapeutic scheme and working in MDTM process for better decision reproducibility(14). The MDTM appears as an answer to this need of optimizing the care process.ConclusionIn our study we showed a reliability and r eproducibility of decision made at MDTM. Reproducibility is acquired when recommendations are well defined. This is proved for localized prostate cancer. On the other hand decisions for advanced prostate cancer were less reproducible even if decisions were made in the setting of recommendations of French Urologist association. These last cases justify more entry in the MDTM in the purpose to standardize the care process, facilitate inclusion in trial. This will allow having well-defined recommendations for complex cases of prostate cancer, and leading to best reproducibility of decision made at MDTM.BIBLIOGRAPHYHeidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. European urology. 200853(1)68-80. Epub 2007/10/09.Salomon L, Azria D, Bastide C, et al. Recommendations Onco-Urology 2010 Prostate cancer. Progres en urologie journal de lAssociation francaise durologie et de la Societe francaise durologie. 201020 Suppl 4S217-51. Epub 2010/12/07. Recommandations en Onc o-Urologie 2010 Cancer de la prostate.Plan cancer 2003-2007 (French Government Law ) http//www.afssa.fr/ET/DocumentsET/plan cancer.pdfVerdecchia A, Francisci S, Brenner H, et al. Recent cancer survival in Europe a 2000- 02 tip analysis of EUROCARE-4 data. The lancet oncology. 20078(9)784-96. Epub 2007/08/24.Berrino F, De Angelis R, Sant M, et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99 results of the EUROCARE-4 study. The lancet oncology. 20078(9)773-83. Epub 2007/08/24.Bergeri I, Michel R, Boutin JP. Everything (or almost everything) about the Kappa coefficient. Medecine tropicale revue du Corps de sante colonial. 200262(6)634-6. Epub 2003/05/07. pepper tout savoir ou presque sur le coefficient Kappa.Acher PL, Young AJ, Etherington-Foy R, McCahy PJ, Deane AM. Improving outcomes in urological cancers the impact of multidisciplinary team meetings. Int J Surg. 20053(2)121-3. Epub 2007/04/28.Van Belle S. How to implement the multidisciplinary approach in prostate cancer management the Belgian model. BJU international. 2008101 Suppl 22-4. Epub 2008/03/01.Sternberg CN, Krainer M, Oh WK, et al. The medical management of prostate cancer a multidisciplinary team approach. BJU international. 200799(1)22-7. Epub 2006/09/08.Nguyen TD, Legrand P, Devie I, Cauchois A, Eymard JC. Qualitative assessment of the multidisciplinary tumor board in breast cancer. Bulletin du cancer. 200895(2)247-51. Epub 2008/02/29. Evaluation qualitative de la reunion de concertation pluridisciplinaire de cancerologie mammaire.Carducci MA, Carroll PR. Multidisciplinary management of advanced prostate cancer changing perspectives on referring patients and enhancing collaboration between oncologists and urologists in clinical trials. Urology. 200565(5 Suppl)18-22 discussion Epub 2005/05/12.Spencer BA, Miller DC, Litwin MS, et al. Variations in quality of care for men with early-stage prostate cancer. Journal of clinical oncology officia l journal of the American Society of clinical Oncology. 200826(22)3735-42. Epub 2008/08/02.Clarke MG, Wilson JR, Kennedy KP, MacDonagh RP. clinical judgment analysis of the parameters used by consultant urologists in the management of prostate cancer. The Journal of urology. 2007178(1)98-102. Epub 2007/05/15.Wilson J, Kennedy K, Ewings P, Macdonagh R. Analysis of consultant decision- making in the management of prostate cancer. Prostate cancer and prostatic diseases. 200811(3)288-93. Epub 2007/10/31.Table1Baselinecharacteristicsofpatientsgroupandt-testof independent sampleFigure 1 Therapeutic decisions made for pT3aN0M0 group at MDTM 1 and 2Figure 2 Therapeutic decisions made for pT3bN0M0 group at MDTM 1 and 2APPENDIX 1Initial location Date of diagnosis DD/MM/YYYY Clinical TNM stagePathology result (specimen) pT XX pN XX M XX Status margin (R) RxMotive Diagnosis Therapeutic decision Therapeutic valuation reserve Surveillance after treatment Another motiveMedical history Result of exams (ex CT scan, MRI, Bone scan, medical notice of colleague )Patients choice WHO general health status 0 1 2 3 4 ComorbiditiesTherapeutic suggestion Final thrapeutic decision