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Small renal mass biopsies: An effective tool in avoiding unnecessary surgery
Poster Session, Sunday 29 January 2017 experiments in solid tumors. The aim of our study was to establish a rabbit para-renal cancer model using locally implanted VX2 tumors. Methods: In order to generate a rabbit model of para-renal cancer, we established four hind limb donor rabbits by using frozen VX2 tumor samples. Following inoculation, rabbits were monitored for appetite and signs of pain. Viable tumors appeared as palpable nodules within 2 weeks of inoculation. Tumor growth was confirmed in all rabbits by high-resolution ultrasound analysis and histology. Once tumor growth was established, hind limb tumors extraction was used for tumor line propagation and para-renal tumor creation. Twenty-one rabbit models bearing para-renal cancer were established by implanting VX2 tumor into the para-renal capsula. Tumors developed into discreet 2−3 cm nodules within 1−3 weeks of implantation. Serial renal ultrasonography follow-up, starting one week after tumor implantation, was performed. Two weeks after tumor implantation, rabbits were euthanized and tumors and other organs were collected for histopathology. Results: Tumor growth after VX2 tumor fragment implantation was confirmed in all rabbits by high-resolution ultrasound (US) imaging examinations of the para-renal regions and was measured with digital caliper. The para-renal injection of VX2 tumor fragments, achieved tumor growth in 100% of cases. All data were confirmed by histological analysis. Conclusions: We generated for the first time, a model of para-renal cancer by surgical tumor implantation of VX2 frozen tumor fragments into rabbit’s para-renal region. This method minimizes the development of metastases and the use of non-necrotic tumors and will optimize the evaluation of tumor response to loco-regional therapy experiments. No conflict of interest. 2171 POSTER Diagnostic of the prostate cancer recurrence in patients after radical prostatectomy by multiparametric MRI vs PET/CT F. Kossov1 , G. Hagverdiyeva2 , V. Panov3 , I. Tyurin2 , E. Tarachkova2 , J. Suraeva3 , I. Gubskiy1 . 1 Russian Onkology Research Center, Radiology, Moscow, Russian Federation; 2 Russian Cancer Research Center, Radiology, Moscow, Russian Federation; 3 Russian Oncology Research Center, Radiology, Moscow, Russian Federation Introduction: The clinical suspicion of local recurrence of prostate cancer (PCa) after radical prostatectomy (RP) is based on the onset of a biochemical failure. Multiparametric MRI (mpMRI) seems to be one of the best method to identify local manifestations of disease progression. This issue is particularly relevant in patients suitable for salvage radiotherapy. Material and Methods: Prostate T2WI, DWI with ADC, and dynamic contrast enhanced (DCE) T1WI were obtained on Magnetom Espree 1.5T (DWI with b = 50–1000–1500) and Skyra 3.0T 3.0T (DWI with b = 50– 1500–2000) (Siemens, Germany) in patients suspicious for local relapse of prostate cancer after radical prostatectomy before salvage radiotherapy. Results: 87 patients with biochemical relapse of PCa after radical prostatectomy examined by mpMRI. The local recurrence of PCa diagnosed in 42 cases. MRI characters of cancer recurrence where the same as for the primary PCa − it was additional tissue in the zone of removed prostate (sizes were from 4 mm till 8 mm): with hypointensive signal on T2WI, hyperintensive signal on DWI with high b value and hypointensive signal on ADC map; with fast and high local uptake (wash in) during DCE examination. MR-contrast agent pharmacokinetics dramatically changed on the background of hormone therapy. APET/CT had shown bone metastasis in 18 patient from 45 cases where mpMRI had not found the local prostate cancer recurrence. Combination of hormone therapy and subsequent salvage radiotherapy improves treatment efficacy of local prostate cancer recurrence. Discussion: mpMRI is unique among radiation diagnostic methods in the evaluation of patients with biochemical recurrence of PCa after radical prostatectomy. The successful results of salvage radiotherapy also serve as a method of verification of the diagnosis (ex juvantibus). If you suspect the presence of a local recurrence of the tumor in the place of removed prostate mpMRI allows you to choose the right tactics treatment. Relapses PCa characterized by the hypointense signal on T2WI, DWI and decreased diffusion coefficient on the ADC, high-speed storage CE and absolute maximum signal intensity at DCE. The results of these studies show that the use of the full complex of MRI methods increases the efficiency of the diagnosis of local recurrence of PCa after radical prostatectomy. Conclusions: mpMRI is the method of choice in patients with biochemical recurrence after radical prostatectomy to avoid local recurrence of PCa in the early stages of its occurrence. mpMRI is required to be applied in patients with biochemical relapse in cases of suspected local recurrence of the tumor, even when the negative results of the integrated TRUS. Most preferably use of this method in assessing the dynamics of local PCa recurrence after radiotherapy in these patients. No conflict of interest.
Abstracts
S189
2172 POSTER Prognostic factors in germ cell cancer − a population based study 1 G. Camara ˆ , J. Silva2 , M. Ramos2 , S. Esteves3 , A. Moreira2 , A. Miranda4 , M. Brito2 . 1 IPOLFG, Medical Oncology, Lisbon, Portugal; 2 Instituto ˆ de Oncologia Francisco Gentil de Lisboa, Medical Oncology, Portugues ˆ de Oncologia Francisco Gentil Lisbon, Portugal; 3 Instituto Portugues ˜ Clinica, Lisbon, Portugal; 4 Instituto de Lisboa, Unidade de Investiga¸cao ˆ de Oncologia Francisco Gentil de Lisboa, Registo Oncologico ´ Portugues Regional Do Sul, Lisbon, Portugal
Background: The prognostic factors in germ cell cancer (GCC) are not totally settled. The International Germ Cell Cancer Collaborative Group Classification (IGCCCGC) and the American Joint Committee on Cancer (AJCC) staging are the current prognostic models available in the clinical practice but some authors suggest the need to review these models in a contemporary population. Our aim was to validate the established prognostic classifications in a recent population cohort and test new factors that may impact the outcome of GCC. Material and Methods: Portuguese registry population-based retrospective study of GCC patients (2008–2012). Brain GCC was excluded. Outcomes assessed were overall survival (OS) and progression free survival (PFS). Survival was calculated by Kaplan–Meier method. Patient age, IGCCCGC, AJCC staging, tumor size and vascular invasion were evaluated. Health care indicators as time between first GCC symptom to diagnosis, diagnosis and start of chemotherapy and compliance to GCC treatment guidelines were also tested. Log-rank test and Cox regression models were used for uni and multivariable analyses. Results: 406 GCC patients were included with a median age of 32 years (range 16−84). Histology was 50% seminoma and 48% non-seminoma (2% unknown) and 13% had vascular invasion. By stage, 54% were I, 18% II and 15% III (13% unknown). According to the IGCCCGC, 81% had good, 5% intermediate, 7% poor prognosis (7% unknown). Median time from first symptom to diagnosis was 2.1 months (range 0.1–58.2) and from diagnosis to start of chemotherapy was 4.2 months (range 0.05–16.4). There was 31% of non-compliance to treatment guidelines. The 5-year OS was 95% (95% CI 93−97%) and PFS was 86% (95% CI 82−90%). At the multivariate level, only IGCCCGC and older age had adverse impact in both OS and PFS (p = 0.010 and p = 0.006, respectively). A trend for a negative impact on OS with non-compliance to treatment guidelines was found. Longer time from diagnosis to chemotherapy in advanced stages was significantly associated with worse PFS. Conclusions: In our population, we confirmed the prognostic relevance of the IGCCCGC and age but not AJCC staging. Older age has been recently described as a prognostic factor but additional investigation is needed. Health care indicators didn’t seem to majorly influence the outcome of GCC patients. No conflict of interest. 2173 POSTER Small renal mass biopsies: An effective tool in avoiding unnecessary surgery A. McPhee1 , A. Ali2 , H. Rush2 , G. Oades2 . 1 Glasgow Royal Infirmary, Dept. of Urology, Glasgow, United Kingdom; 2 Queen Elizabeth University Hospital, Dept. of Urology, Glasgow, United Kingdom Background: There has been in increasing incidence of Small Renal Masses (SRMs) over the past decade in keeping with the global increasing incidence in RCC seen over the past decades. Studies have shown that between 20−30% of small renal masses are benign, but as yet we are unable to reliably distinguish between benign and malignant disease radiologically. Renal biopsy has been established as a safe and reliable technique to obtain information on the pre-treatment histology of renal masses. However adoption by the urological community as a standard approach to guiding treatment remains low, as the available evidence is for high volume centres. Objective: We proposed to validate the safety, accuracy and reliability of renal biopsy in our centre. And to evaluate the effectiveness of using biopsies to guide treatment decision for small renal mass biopsies. Materials and Methods: We conducted a retrospective study of patients who underwent SRM biopsy between 2013 and April 2016. Patients were identified using the prospectively maintained electronic patient record system (Clinical Portal) and our pathology database (Telepath). Diagnostic and concordance rates will be presented as proportions. Results: A total of 208 renal biopsied SRMs were included in the analysis and the comparison with other high volume centres can be seen in Table 1. Of the biopsied masses, the initial biopsy was diagnostic in 88% (n = 184) of cases, of which 16.43 (n = 34) were found to benign. Only 1 patient had an adverse event 0.5% requiring a blood transfusion for post biopsy bleeding (Clavien-Dindo Grade II).
S190
Abstracts
Poster Session, Sunday 29 January 2017
Table 1. Study
Years
No of tumours
Mean size
Nondiagnostic
Diagnostic
Benign
Malignant
Our study Richard et al.
2013–2016 2011–2015
208 373
12% 13%
88% 87%
16.3% 18%
71.6% 82%
Jeon et al. Richard, Jewet, Bhatt et al. Prince et al.
2008–2015 2001–2013
442 529
2.74 2.6 (median) 2.3 2.5
11.1% 10%
88.9% 90%
21.3% 23.4%
67.6% 66.6%
2000–2014
413
17.4%
82.6%
Leveridge et al. Menogue et al.
2000–2009 1998–2009
345 268
Not reported 2.5 2.5
19.4% 20%
80.6% 80%
Not reported 16.6% 20.8%
Not reported 64% 59.2%
Concordance rates have improved with time and recent series from Richard et al. in Toronto have shown concordance rates of 90%. Our series has a 100% concordance rate for biopsy with surgical histology. We did not routinely report grading on renal biopsy so we cannot confirm if this level of concordance would apply to grading of tumours. Conclusion: The present study provides further evidence of the benefit of renal biopsy. With the increasing use of imaging, an increasing number of SRMs are being diagnosed. The majority of SRMs are still being treated with up front definitive treatment, which results in over treatment. Consequently, for patients in whom definitive treatment is being considered, we believe that biopsy of SRM is a way to reduce over treatment, the cost of treatment and, more importantly, limit treatment-related morbidity. No conflict of interest. 2174 POSTER Relevance of pVHL expression in biological profile of renal cell carcinomas A. Singhai1 , S. Babu1 , B.P. Singh2 . 1 King George’s Medical University, Pathology, Lucknow, India; 2 King George’s Medical University, Urology, Lucknow, India Background: Von Hippel Lindau (VHL) is the tumor suppressor gene; alterations in gene product (pVHL) of which leads to development of Renal Cell Carcinoma (RCC). pVHL functions through transcription dependent nuclear-cytoplasmic trafficking for it’s action. Present study is an aim to evaluate and correlate the frequency of pVHL expression with different Renal Carcinoma subtypes, grades and stages. Material and Methods: A total of 78 cases of RCC which included three subtypes viz. clear cell, papillary and chromophobe were analyzed for pVHL expression using polyclonal antibody to pVHL (pVHL30/pVHL19). Age of the patients varied from 05 to 70 years with a mean age of 54.5±12 years. Of these 70 cases expressed positivity. Among these 55, 11 and 04 were clear cell, papillary and chromophobe respectively. Stage wise distribution of these cases was as 44% (I), 28% (II), 18% (III) and 10% (IV). Results: pVHL expression across tumor cells was predominantly nucleocytoplasmic (83%) followed by exclusive cytoplasmic (11%) and nuclear (06%) expressions. TNM staging wise, exclusive nuclear expression was confined to early stages (I and II) only, whereas cytoplasmic exclusivity showed a predominant predilection for advanced stages viz. 23% and 29% for stages III and IV as against 6% in early stages (I and II). Nucleocytoplasmic expression also was skewed towards early stages (84%) as compared to locally metastatic (77%) and advanced metastatic (71%) stages. Fuhrman’s nuclear grading in clear cell RCC cases too accounted for all the exclusive nuclear positive pVHL expression in grade I while the cytoplasmic alone expressive pVHL cases shared 60% of grade IV labeled carcinomas. Statistical significance was achieved for most of the results. Conclusions: To conclude, the results emphasize that VHL gene mutations leading to structural alterations in pVHL have significant relevance in biological profile of Renal Cell Carcinomas. No conflict of interest.
2175 POSTER Outcome of oligoprogressing metastatic renal cell carcinoma patients treated with locoregional therapy: A multicenter retrospective analysis D. De Lisi1 , M. Maruzzo2 , L. Galli3 , E. Biasco3 , A. Farnesi3 , G. Procopio4 , R. Ratta4 , S. Buti5 , C.N. Sternberg6 , L. Cerbone6 , G. Di Lorenzo7 , F. Pantano8 , M. Sterpi1 , U. De Giorgi9 , R. Berardi10 , M. Torinai10 , A. Camerini11 , F. Massari12 , G. Tonini8 , D. Santini8 . 1 Campus Bio-Medico University of Rome- Rome- Italy, Department of Medical Oncology, Rome, Italy; 2 Istituto Oncologico Veneto- IRCCS- Padova- Italy, Medical Oncology 1, Padova, Italy; 3 Azienda Ospedaliera Universitaria PisanaPisa- Italy, U.O. Oncologia Universitaria, Pisa, Italy; 4 Fondazione IRCCS Istituto Nazionale dei Tumori- Milan- Italy, Department of Medical Oncology, Milano, Italy; 5 University Hospital of Parma- Via Gramsci- 1443126 Parma, Oncology Unit, Parma, Italy; 6 San Camillo and Forlanini Hospitals- Padiglione Flajani- Circonvallazione Gianicolense 87- Rome00152- Italy, Department of Medical Oncology, Roma, Italy; 7 Universita` degli Studi Federico II, Universita` degli Studi Federico II- Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica − Naples − Italy, Napoli, Italy; 8 Campus Bio-Medico University of Rome- Rome- Italy, Department of Medical Oncology, Roma, Italy; 9 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori I.R.S.T. IRCCS- Meldola, Department of Medical Oncology, Roma, Italy; 10 AOU Ospedali Riuniti- Universita` Politecnica delle Marche- Ancona- Italy, Department of Medical Oncology, Ancona, Italy; 11 Versilia Hospital and Istituto Toscano Tumori - Lido di Camaiore LU − Italy, Medical Oncology, Lido di Camaiore, Italy; 12 S.OrsolaMalpighi Hospital- Bologna- Italy, Division of Oncology, Bologna, Italy Background: No survival outcomes about continuing the same targeted therapy beyond progression or switching to second line options are available in patients with metastatic renal cell carcinoma (mRCC) who progressed in one more or metastatic sites radically treated with locoregional treatments. Patients and Methods: 55 mRCC patients were retrospectively analyzed. Post-first-progression free survival (PFPFS) and post-first-progression overall survival (PFPOS) in patients who continued the same TT versus those who switched to another TT after locoregional treatment were analyzed via the Kaplan–Meier method and Mantel–Haenszel log-rank test. A Cox-regression model was applied to the data with a univariate and multivariate approach in order to analyzed possible predictive and prognostic factors of PFPFS and PFPOS. Results: The global median post-first-progression OS (mPFPOS) and PFS (mPFPFS) were 37 months (95% CI 25.2–48.7) and 14 months (95% CI 6.9−21) respectively. Patients who continued the same therapy after a locoregional treatment on a site of progression had a significantly longer mPFPOS compared to patients who switched to another therapy (39 vs 11 months, p = 0.014). An advantage in mPFPOS was also observed in patients with a good risk score compared to patients of the intermediate risk group (39 vs 29 months, p = 0.036) and in patients with bone metastases versus visceral metastases (not reached [NR] vs 31 months, p = 0.045). At multivariate analysis, change of treatment after first progression (p = 0.008, HR 4.140) and bone metastases as site of first progression (p = 0.041, HR 0.456) were independent predictive factors of poorer and better prognosis in terms of mPFPOS respectively. Considering mPFPFS, patients with Fuhrman grade 2 and ECOG PS of 0 or 1 had a longer mPFOPFS compared to patients with a PS or more than 1 (14 vs 7, p = 0.065) and Fuhrman grade of 1, 3 and 4 (22 vs 4 vs 10 vs 6 months, p = 0.009) respectively. No statistically significant differences in terms of PFPFS were observed between patients who continued the same treatment after disease oligo-progression and those who changed therapy (15 vs 7 moths, p = 0.207). Conclusions: Locoregional treatments represent an option for oligometastatic mRCC treated with TT. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site appear to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome. Furthermore no difference in terms of progression free survival was found between patients who continued the same TT and patients who switched to another TT. No conflict of interest.
Abstracts
S189
2172 POSTER Prognostic factors in germ cell cancer − a population based study 1 G. Camara ˆ , J. Silva2 , M. Ramos2 , S. Esteves3 , A. Moreira2 , A. Miranda4 , M. Brito2 . 1 IPOLFG, Medical Oncology, Lisbon, Portugal; 2 Instituto ˆ de Oncologia Francisco Gentil de Lisboa, Medical Oncology, Portugues ˆ de Oncologia Francisco Gentil Lisbon, Portugal; 3 Instituto Portugues ˜ Clinica, Lisbon, Portugal; 4 Instituto de Lisboa, Unidade de Investiga¸cao ˆ de Oncologia Francisco Gentil de Lisboa, Registo Oncologico ´ Portugues Regional Do Sul, Lisbon, Portugal
Background: The prognostic factors in germ cell cancer (GCC) are not totally settled. The International Germ Cell Cancer Collaborative Group Classification (IGCCCGC) and the American Joint Committee on Cancer (AJCC) staging are the current prognostic models available in the clinical practice but some authors suggest the need to review these models in a contemporary population. Our aim was to validate the established prognostic classifications in a recent population cohort and test new factors that may impact the outcome of GCC. Material and Methods: Portuguese registry population-based retrospective study of GCC patients (2008–2012). Brain GCC was excluded. Outcomes assessed were overall survival (OS) and progression free survival (PFS). Survival was calculated by Kaplan–Meier method. Patient age, IGCCCGC, AJCC staging, tumor size and vascular invasion were evaluated. Health care indicators as time between first GCC symptom to diagnosis, diagnosis and start of chemotherapy and compliance to GCC treatment guidelines were also tested. Log-rank test and Cox regression models were used for uni and multivariable analyses. Results: 406 GCC patients were included with a median age of 32 years (range 16−84). Histology was 50% seminoma and 48% non-seminoma (2% unknown) and 13% had vascular invasion. By stage, 54% were I, 18% II and 15% III (13% unknown). According to the IGCCCGC, 81% had good, 5% intermediate, 7% poor prognosis (7% unknown). Median time from first symptom to diagnosis was 2.1 months (range 0.1–58.2) and from diagnosis to start of chemotherapy was 4.2 months (range 0.05–16.4). There was 31% of non-compliance to treatment guidelines. The 5-year OS was 95% (95% CI 93−97%) and PFS was 86% (95% CI 82−90%). At the multivariate level, only IGCCCGC and older age had adverse impact in both OS and PFS (p = 0.010 and p = 0.006, respectively). A trend for a negative impact on OS with non-compliance to treatment guidelines was found. Longer time from diagnosis to chemotherapy in advanced stages was significantly associated with worse PFS. Conclusions: In our population, we confirmed the prognostic relevance of the IGCCCGC and age but not AJCC staging. Older age has been recently described as a prognostic factor but additional investigation is needed. Health care indicators didn’t seem to majorly influence the outcome of GCC patients. No conflict of interest. 2173 POSTER Small renal mass biopsies: An effective tool in avoiding unnecessary surgery A. McPhee1 , A. Ali2 , H. Rush2 , G. Oades2 . 1 Glasgow Royal Infirmary, Dept. of Urology, Glasgow, United Kingdom; 2 Queen Elizabeth University Hospital, Dept. of Urology, Glasgow, United Kingdom Background: There has been in increasing incidence of Small Renal Masses (SRMs) over the past decade in keeping with the global increasing incidence in RCC seen over the past decades. Studies have shown that between 20−30% of small renal masses are benign, but as yet we are unable to reliably distinguish between benign and malignant disease radiologically. Renal biopsy has been established as a safe and reliable technique to obtain information on the pre-treatment histology of renal masses. However adoption by the urological community as a standard approach to guiding treatment remains low, as the available evidence is for high volume centres. Objective: We proposed to validate the safety, accuracy and reliability of renal biopsy in our centre. And to evaluate the effectiveness of using biopsies to guide treatment decision for small renal mass biopsies. Materials and Methods: We conducted a retrospective study of patients who underwent SRM biopsy between 2013 and April 2016. Patients were identified using the prospectively maintained electronic patient record system (Clinical Portal) and our pathology database (Telepath). Diagnostic and concordance rates will be presented as proportions. Results: A total of 208 renal biopsied SRMs were included in the analysis and the comparison with other high volume centres can be seen in Table 1. Of the biopsied masses, the initial biopsy was diagnostic in 88% (n = 184) of cases, of which 16.43 (n = 34) were found to benign. Only 1 patient had an adverse event 0.5% requiring a blood transfusion for post biopsy bleeding (Clavien-Dindo Grade II).
S190
Abstracts
Poster Session, Sunday 29 January 2017
Table 1. Study
Years
No of tumours
Mean size
Nondiagnostic
Diagnostic
Benign
Malignant
Our study Richard et al.
2013–2016 2011–2015
208 373
12% 13%
88% 87%
16.3% 18%
71.6% 82%
Jeon et al. Richard, Jewet, Bhatt et al. Prince et al.
2008–2015 2001–2013
442 529
2.74 2.6 (median) 2.3 2.5
11.1% 10%
88.9% 90%
21.3% 23.4%
67.6% 66.6%
2000–2014
413
17.4%
82.6%
Leveridge et al. Menogue et al.
2000–2009 1998–2009
345 268
Not reported 2.5 2.5
19.4% 20%
80.6% 80%
Not reported 16.6% 20.8%
Not reported 64% 59.2%
Concordance rates have improved with time and recent series from Richard et al. in Toronto have shown concordance rates of 90%. Our series has a 100% concordance rate for biopsy with surgical histology. We did not routinely report grading on renal biopsy so we cannot confirm if this level of concordance would apply to grading of tumours. Conclusion: The present study provides further evidence of the benefit of renal biopsy. With the increasing use of imaging, an increasing number of SRMs are being diagnosed. The majority of SRMs are still being treated with up front definitive treatment, which results in over treatment. Consequently, for patients in whom definitive treatment is being considered, we believe that biopsy of SRM is a way to reduce over treatment, the cost of treatment and, more importantly, limit treatment-related morbidity. No conflict of interest. 2174 POSTER Relevance of pVHL expression in biological profile of renal cell carcinomas A. Singhai1 , S. Babu1 , B.P. Singh2 . 1 King George’s Medical University, Pathology, Lucknow, India; 2 King George’s Medical University, Urology, Lucknow, India Background: Von Hippel Lindau (VHL) is the tumor suppressor gene; alterations in gene product (pVHL) of which leads to development of Renal Cell Carcinoma (RCC). pVHL functions through transcription dependent nuclear-cytoplasmic trafficking for it’s action. Present study is an aim to evaluate and correlate the frequency of pVHL expression with different Renal Carcinoma subtypes, grades and stages. Material and Methods: A total of 78 cases of RCC which included three subtypes viz. clear cell, papillary and chromophobe were analyzed for pVHL expression using polyclonal antibody to pVHL (pVHL30/pVHL19). Age of the patients varied from 05 to 70 years with a mean age of 54.5±12 years. Of these 70 cases expressed positivity. Among these 55, 11 and 04 were clear cell, papillary and chromophobe respectively. Stage wise distribution of these cases was as 44% (I), 28% (II), 18% (III) and 10% (IV). Results: pVHL expression across tumor cells was predominantly nucleocytoplasmic (83%) followed by exclusive cytoplasmic (11%) and nuclear (06%) expressions. TNM staging wise, exclusive nuclear expression was confined to early stages (I and II) only, whereas cytoplasmic exclusivity showed a predominant predilection for advanced stages viz. 23% and 29% for stages III and IV as against 6% in early stages (I and II). Nucleocytoplasmic expression also was skewed towards early stages (84%) as compared to locally metastatic (77%) and advanced metastatic (71%) stages. Fuhrman’s nuclear grading in clear cell RCC cases too accounted for all the exclusive nuclear positive pVHL expression in grade I while the cytoplasmic alone expressive pVHL cases shared 60% of grade IV labeled carcinomas. Statistical significance was achieved for most of the results. Conclusions: To conclude, the results emphasize that VHL gene mutations leading to structural alterations in pVHL have significant relevance in biological profile of Renal Cell Carcinomas. No conflict of interest.
2175 POSTER Outcome of oligoprogressing metastatic renal cell carcinoma patients treated with locoregional therapy: A multicenter retrospective analysis D. De Lisi1 , M. Maruzzo2 , L. Galli3 , E. Biasco3 , A. Farnesi3 , G. Procopio4 , R. Ratta4 , S. Buti5 , C.N. Sternberg6 , L. Cerbone6 , G. Di Lorenzo7 , F. Pantano8 , M. Sterpi1 , U. De Giorgi9 , R. Berardi10 , M. Torinai10 , A. Camerini11 , F. Massari12 , G. Tonini8 , D. Santini8 . 1 Campus Bio-Medico University of Rome- Rome- Italy, Department of Medical Oncology, Rome, Italy; 2 Istituto Oncologico Veneto- IRCCS- Padova- Italy, Medical Oncology 1, Padova, Italy; 3 Azienda Ospedaliera Universitaria PisanaPisa- Italy, U.O. Oncologia Universitaria, Pisa, Italy; 4 Fondazione IRCCS Istituto Nazionale dei Tumori- Milan- Italy, Department of Medical Oncology, Milano, Italy; 5 University Hospital of Parma- Via Gramsci- 1443126 Parma, Oncology Unit, Parma, Italy; 6 San Camillo and Forlanini Hospitals- Padiglione Flajani- Circonvallazione Gianicolense 87- Rome00152- Italy, Department of Medical Oncology, Roma, Italy; 7 Universita` degli Studi Federico II, Universita` degli Studi Federico II- Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica − Naples − Italy, Napoli, Italy; 8 Campus Bio-Medico University of Rome- Rome- Italy, Department of Medical Oncology, Roma, Italy; 9 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori I.R.S.T. IRCCS- Meldola, Department of Medical Oncology, Roma, Italy; 10 AOU Ospedali Riuniti- Universita` Politecnica delle Marche- Ancona- Italy, Department of Medical Oncology, Ancona, Italy; 11 Versilia Hospital and Istituto Toscano Tumori - Lido di Camaiore LU − Italy, Medical Oncology, Lido di Camaiore, Italy; 12 S.OrsolaMalpighi Hospital- Bologna- Italy, Division of Oncology, Bologna, Italy Background: No survival outcomes about continuing the same targeted therapy beyond progression or switching to second line options are available in patients with metastatic renal cell carcinoma (mRCC) who progressed in one more or metastatic sites radically treated with locoregional treatments. Patients and Methods: 55 mRCC patients were retrospectively analyzed. Post-first-progression free survival (PFPFS) and post-first-progression overall survival (PFPOS) in patients who continued the same TT versus those who switched to another TT after locoregional treatment were analyzed via the Kaplan–Meier method and Mantel–Haenszel log-rank test. A Cox-regression model was applied to the data with a univariate and multivariate approach in order to analyzed possible predictive and prognostic factors of PFPFS and PFPOS. Results: The global median post-first-progression OS (mPFPOS) and PFS (mPFPFS) were 37 months (95% CI 25.2–48.7) and 14 months (95% CI 6.9−21) respectively. Patients who continued the same therapy after a locoregional treatment on a site of progression had a significantly longer mPFPOS compared to patients who switched to another therapy (39 vs 11 months, p = 0.014). An advantage in mPFPOS was also observed in patients with a good risk score compared to patients of the intermediate risk group (39 vs 29 months, p = 0.036) and in patients with bone metastases versus visceral metastases (not reached [NR] vs 31 months, p = 0.045). At multivariate analysis, change of treatment after first progression (p = 0.008, HR 4.140) and bone metastases as site of first progression (p = 0.041, HR 0.456) were independent predictive factors of poorer and better prognosis in terms of mPFPOS respectively. Considering mPFPFS, patients with Fuhrman grade 2 and ECOG PS of 0 or 1 had a longer mPFOPFS compared to patients with a PS or more than 1 (14 vs 7, p = 0.065) and Fuhrman grade of 1, 3 and 4 (22 vs 4 vs 10 vs 6 months, p = 0.009) respectively. No statistically significant differences in terms of PFPFS were observed between patients who continued the same treatment after disease oligo-progression and those who changed therapy (15 vs 7 moths, p = 0.207). Conclusions: Locoregional treatments represent an option for oligometastatic mRCC treated with TT. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site appear to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome. Furthermore no difference in terms of progression free survival was found between patients who continued the same TT and patients who switched to another TT. No conflict of interest.