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.

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.

[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.

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.

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.