Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study.

BACKGROUND: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. PATIENTS AND METHODS: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics. RESULTS: Overall, 216 patients were randomized to gatipotuzumab (n  = 151) or placebo (n  = 65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P  = 0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events. CONCLUSIONS: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.govNCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599.

Effect of adjuvant chemotherapy in locally advanced urothelial carcinoma of the bladder treated with cystectomy. / Efecto de la quimioterapia adyuvante en el carcinoma urotelial de vejiga localmente avanzado tratado con cistectomía.

INTRODUCTION: Currently, the role of adjuvant chemotherapy (ADJ) in muscle invasive bladder tumor remains controversial. OBJECTIVE: To evaluate the effect of ADJ on cancer specific survival of muscle invasive bladder tumor after radical cystectomy (RC). MATERIAL AND METHODS: Retrospective analysis of 292 patients diagnosed with urothelial bladder tumor pT3-4pN0 / + cM0 stage, treated with RC between 1986-2009. Total cohort was divided in two groups: 185 (63.4%) patients treated with ADJ and 107 (36.6%) without ADJ. Median follow-up was 40.5 months (IQR 55-80.5). Comparative analysis was performed with Chi-square test and Student's t test /ANOVA. Survival analysis was carried out with the Kaplan-Meier method and log-rank test. Multivariate analysis (Cox regression) was made to identify independent predictors of cancer-specific mortality (CSM). RESULTS: 42.8% of the series presented lymph node involvement after RC. At the end of follow-up, 22.9% were BC-free and 54.8% had died due to this cause. The median cancer specific survival was 30 months. No significant differences were observed in cancer specific survival regarding the treatment with ADJ in pT3pN0 (p=.25) or pT4pN0 (p=.29) patients, but it was significant in pT3-4pN+ (p=.001). Multivariate analysis showed pathological stage (p=.0001) and treatment with ADJ (p=.007) as independent prognostic factors for CSM. ADJ reduced the risk of CSM (HR:0.59,95% CI 0.40-0.87, p=.007). CONCLUSIONS: pT and pN stages were identified as independent predictors of CSM after RC. The administration of ADJ in our series behaved as a protective factor reducing the risk of CSM, although only pN+ patients were benefited in the stage analysis.

Salvage lymph node dissection in patients with prostate cancer treated with radical prostatectomy or radiotherapy and positive choline positron emission tomography (PET/CT) scan. / Linfadenectomía de rescate en pacientes con cáncer de próstata tratados con prostatectomía radical o radioterapia y tomografía por emisión de positrones (PET) con colina positiva.

INTRODUCTION AND OBJECTIVES: Nodal prostate cancer recurrence is a challenging scenario. Current guidelines recommend the use of androgen deprivation therapy, tailored treatment or clinical trials. We studied the impact of Salvage lymph node dissection in selected patients. MATERIAL AND METHODS: We retrospectively reviewed records of 23 consecutive patients with prostate cancer and previous Radical prostatectomy or Radiotherapy who underwent SLND from December 2005 to November 2015. RESULTS: We found that in patients that showed biochemical response the introduction of ADT was delayed 14.9 months compared to patients that did not responded (2.8 months) P=.00026. Furthermore although statistical significance was not reached (P=.072) PSA-DT could be a potential prognostic factor of radiological recurrence since patients with PSA-DT<6 months developed radiological recurrence 7.6 months earlier compared to their counterparts. CONCLUSIONS: Salvage lymph node dissection is a potential treatment that could delay ADT in selected patients.

Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study.

BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.

Synchronous versus metachronous brain metastasis from testicular germ cell tumors (TGCT): an analysis from the Spanish Germ Cell Cancer Group data base

BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution (AU)

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Synchronous versus metachronous brain metastasis from testicular germ cell tumors (TGCT): an analysis from the Spanish Germ Cell Cancer Group data base.

BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.

SEOM clinical guidelines for treatment of prostate cancer

Prostate cancer (PC) is the most common cancer in men. Many patients have prolonged survival and die of other diseases, so treatment decisions are often influenced by age and coexisting comorbidities. The main procedure to diagnose PC is an ultrasound-guided core needle biopsy, which is indicated when a digital rectal examination (DRE) finds nodularity or when PSA is >10 ng/ml, but is also recommended with PSA between 4.0 and 10 ng/ml. Depending on age, PSA, Gleason score and characteristics of the tumour, treatment options for localised PC are active surveillance, radical prostatectomy and radiation therapy. Androgen deprivation treatment (ADT) should be added to radiotherapy for men with intermediate- or high-risk PC. ADT is the current standard first-line treatment for metastatic PC. Castration-resistant PC is a heterogeneous entity. Several treatments such as sipuleucel-T, docetaxel-based chemotherapy, radium 223, cabazitaxel or abiraterone plus prednisone, zoledronic and denosumab, are useful for this situation (AU)

[Mediastinal germ-cell tumours]. / Tumores germinales mediastínicos.

Germ-cell tumours of male ussually arise from the testis. However, in 2-5% of the cases, they also occur outside of the testis as a primary site without evidence of testicular primary tumour. This infrequent entity often appears in the body midline, predominantly in mediastinum and retroperitoneum. Mediastinal germ-cell tumours (MGCT) shall be included in the differential diagnosis of any mediastinic tumour of unknown origin. An accurate diagnosis is essential, due to the fact that these tumours are curable with chemotherapy. The histopathologic and clinical features, and its differences with germ-cell tumours from testicular origin are revised in this article.

Tumores germinales mediastínicos / Mediastinal germ-cell tumours

Los tumores de células germinales del varón habitualmente se originan en los testículos. Sin embargo, en el 2-5% de los casos pueden aparecer de forma primaria en localizaciones extragonadales, sin evidencia de un tumor testicular. Esta infrecuente entidad suele aparecer en la línea media corporal, predominántemente en el mediastino y en el retroperitoneo. Los tumores germinales extragonadales mediastínicos (TGEM) deben incluirse en el diagnóstico diferencial de cualquier tumor mediastínico de origen desconocido. Un diagnóstico exacto es fundamental, debido a que son tumores potencialmente curables con quimioterapia. En este artículo se revisan las características histopatológicas y clínicas de losTGEM, y sus diferencias los tumores germinales de origen testicular

Germ-cell tumours of male ussually arise from the testis. However, in 2-5% of the cases, they also occur outside of the testis as a primary site without evidence of testicular primary tumour. This infrequent entity often appears in the body midline, predominantly in mediastinum and retroperitoneum. Mediastinal germ-cell tumours (MGCT) shall be included in the differential diagnosis of any mediastinic tumour of unknown origin. An accurate diagnosis is essential, due to the fact that these tumours are curable with chemotherapy. The histopathologic and clinical features, and its differences with germ-cell tumours from testicular origin are revised in this article

False-positive beta-human chorionic gonadotropin values in the follow-up of gestational trophoblastic disease.

Gestational trophoblastic disease consists of a pathological spectrum of entities from molar pregnancies, which are premalignant conditions, to malignant invasive choriocarcinoma. Serum Beta-human chorionic gonadotropin (hCG) levels are essential both in the diagnosis and in the follow-up. There are high rates of complete responses and long-term survivors, because of the excellent chemosensitivity of these tumours. After initial management, an increased level of Beta-hCG indicates persistent disease. However, in the absence of evidence of persistent disease, false-positive Beta-hCG values may be considered. We present here the case of a woman with a metastatic choriocarcinoma in complete response after chemotherapy, who developed later persistent false-positive values of Beta-hCG in the follow-up. Causes of false-positive Beta-hCG determinations are revised.

False-positive beta-human chorionic gonadotropin values in the follow-up of gestational trophoblastic disease

Gestational trophoblastic disease consists of a pathological spectrum of entities from molar pregnancies, which are premalignant conditions, to malignant invasive choriocarcinoma. Serum Beta-human chorionic gonadotropin (hCG) levels are essential both in the diagnosis and in the follow-up. There are high rates of complete responses and long-term survivors, because of the excellent chemosensitivity of these tumours. After initial management, an increased level of Beta-hCG indicates persistent disease. However, in the absence of evidence of persistent disease, false-positive Beta-hCG values may be considered. We present here the case of a woman with a metastatic choriocarcinoma in complete response after chemotherapy, who developed later persistent false-positive values of Beta-hCG in the follow-up. Causes of false-positive Beta-hCG determinations are revised (AU)

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Carcinoma neuroendocrino de células grandes de pulmón. Análisis de una serie de once casos en un hospital universitario / Lung large-cell neuroendocrine carcinoma. Analysis of a series of eleven cases in a universitary hospital

Propósito: Los tumores pulmonares con diferenciación neuroendocrina (DN) son un grupo heterogéneode neoplasias que incluyen tumores carcinoides típicos, carcinoides atípicos, carcinomas neuroendocrinosde células grandes (CNCG) y carcinoma pulmonar de células pequeñas. Los CNCGconstituyen menos del 5% de los carcinomas pulmonares no células pequeñas (CPNCP). En este trabajose describe una serie de CNCG, tratados en un solo centro a lo largo de 10 años.Material y métodos: Se analizan 11 pacientes diagnosticados de CNCG (5 con histologías mixtas).Resultados: La edad media de los pacientes fue de 66 años, 5 fueron varones, 4 tuvieron enfermedadlocalizada, 5 localmente avanzada y 2 diseminada. Siete pacientes, con tumores localizados,fueron tratados con cirugía radical, 2 de ellos recibieron quimioterapia adyuvante; 1 quimioterapia yradioterapia y los otros 3 solo quimioterapia. La mediana de supervivencia de la serie es de 24 meses,y la supervivencia global a 2 y 5 años del 45% y 27% respectivamente.Conclusión: Los datos de nuestra serie corroboran las recomendaciones de que el manejo de losCNCG debe hacerse de forma similar al del resto de los CPNCP. La cirugía radical es el tratamientofundamental en los tumores localizados. No hay datos suficientes que indiquen una peor respuesta alos tratamientos de quimioterapia o radioterapia en este tipo de tumores

Purpose: Lung carcinomas with neuroendocrine differentiation are a heterogeneous group oftumors related to typical and atypical carcinoids, neuroendocrine large-cell carcinomas (NLCC) andsmall-cell lung cancer (SCLC). NLCC comprises less than 5% of non small-cell lung cancer (NSCLC).In this report, we describe a series of NLCC treated in a single institution in the last ten years.Material and methods: Eleven patients diagnosed as having NLCC (5 of them with mixedhistology).Results: At diagnosis, the mean age of the patients was 66 years (5 males and 6 females); 4 hadlocalized disease, 5 locally advanced disease, and 2 metastatic disease. Seven patients underwent initialradical surgery (2 of them followed by adjuvant chemotherapy), 1 patient received chemotherapy andradiotherapy, and 3 patients only chemotherapy. Median overall survival for the whole series was 24months, and the overall 2-year and 5-year survival were 45% and 27% respectively.Conclusion: Our data corroborate the general recommendation of treating NLCC in a similar wayas the rest of the non small-cell lung cancer (NSCLC) are treated. Radical surgery is the maintreatment for localized tumors. There are no data indicating a worse response of these tumors toradiation therapy or chemotherapy

E400P in advanced seminoma of good prognosis according to the international germ cell cancer collaborative group (IGCCCG) classification: the Spanish Germ Cell Cancer Group experience.

PURPOSE: To evaluate the efficacy and toxicity of primary chemotherapy with the schedule E400P in the treatment of patients with early stage II (IIa and IIb) and advanced seminoma of good prognosis according to the international classification (IGCCCG). PATIENTS AND METHODS: Sixty-four patients were included. E400P consisted of cisplatin 25 mg/m2/day and etoposide 100 mg/m2/day for four days, every three weeks. Royal Marsden stages were IIab: 53% and IIc-IV: 47%. Twenty-three percent had high BHCG levels, twenty-seven percent had LDH > 2 x N. Sixty-two patients were of good prognosis according to the Medical Research Council classification. RESULTS: Response rate was 98% (69% complete remission, 29% residual disease). After a median follow-up of 34 months, treatment failure was seen in 7 patients (11%). Neutropenia (32%) was the most relevant grade 3-4 toxicity. Other important grade 3-4 side effects were found in less than 5%. Three-year time to treatment failure (TTF) was 89% (95% confidence intervals (CI): 80%-97%) for all patients, 91% (95% CI: 80%-99%) for stages IIa-b, and 87% (95% CI: 74%-99%) for stages IIc-IV. Three-year overall survival (OS) was 97% (95% CI: 93%-99%) for all patients and 95% (95% CI: 85%-99%) for stages IIa-b. CONCLUSIONS: E400P was a very active and safe regimen in good-prognosis advanced seminoma, with low toxicity rates. Definitive comparisons of this regimen with radiotherapy in stages IIa-b or with the more standard E500P or BEP, could be of interest.

[Primary large cell thyroid lymphoma. Report of 6 cases treated with chemotherapy]. / Linfoma de células grandes primario de tiroides. A propósito de 6 casos tratados con quimioterapia.

A series of 6 cases with primary thyroid lymphoma of aggressive histologic type (large cell lymphoma) is presented. Two patients had previous diagnosis of chronic lymphocytary thyroiditis and one also had ulcerative colitis. The Ann Arbor stage was I-E in 2 patients and II-E in four. LDH level was high in four patients and three had criteria of bulky disease. All developed compressive symptoms. As primary therapy 3 patients received polychemotherapy (ProMACE-CytaBOM). The remaining underwent surgery prior to cytostatic treatment. In the three patients with large tumoral volume complementary radiotherapy was also carried out. Five patients had rapid complete remission with chemotherapy and the other achieved partial response of 75% (had complete remission upon termination of radiotherapy). Five are alive without disease at 87, 47, 25, 23 and 16 months of the onset of treatment. One patient died due to cerebral infarction after the fourth cycle. Polychemotherapy is a good therapeutic option for primary thyroid lymphoma with unfavourable prognostic factors.

Primary renal lymphoma: report of 3 cases and review of the literature.

Primary renal lymphoma is a controversial entity. Only 29 cases have been reported since 1980. Diagnostic criteria are not well established. We report here 3 new cases and review the literature. Primary renal lymphoma was considered on the basis of uni- or bilateral nonobstructive nephromegaly with or without renal failure. In all cases, the diagnosis was made after renal biopsy. Extrarenal abdominal involvement was excluded by imaging techniques. The role of staging laparotomy remains controversial. Chemotherapy is the treatment of choice, but the prognosis is poor. We propose a clinical definition of primary renal lymphoma in order to achieve a better management of the disease.

[Chemotherapy in prostatic carcinoma]. / Quimioterapia en el carcinoma prostático.

Carcinoma of the prostate has been treated by monochemotherapy, polychemotherapy, intraarterial chemotherapy, combined chemo and hormone therapy and growth factor antagonists. Difficulties exist in evaluating the efficacy of chemotherapy due to the scant number of patients treated and the different criteria used to assess response. Monochemotherapy has achieved a response rate (complete and partial) of less than 20% in randomized studies and that obtained with polychemotherapy is only slightly higher. The studies that have been conducted comparing these two treatment modalities have not clearly demonstrated the superiority of the latter. The duration of response is short and is measured in weeks. There is no standard treatment. Adriamycin, fluorouracil and cyclophosphamide appear to be the most effective cytostatic agents. There is no evidence that chemotherapy improves survivorship, and in comparison to symptomatic treatment, the former has been superior. The combination of chemotherapy with hormone therapy as a first line of treatment can improve the response rate slightly and enhance survivorship, although further studies are warranted to determine this definitely. Recruitment with androgens increases the response, but may entail risks. The growth factor antagonists have extended the therapeutic possibilities in prostate carcinoma, but further studies are warranted to determine its true value.