RESUMO
INTRODUCTION: To evaluate the role of unilateral inguinal lymph-node dissection (ILND) plus contralateral dynamic sentinel node biopsy (DSNB) vs. bilateral ILND in clinical N1 (cN1) penile squamous cell carcinoma (peSCC) patients. MATERIAL AND METHODS: Within our institutional database (1980-2020, included), we identified 61 consecutive cT1-4 cN1 cM0 patients with histological confirmed peSCC who underwent either unilateral ILND plus DSNB (26) or bilateral ILND (35). RESULTS: Median age was 54 years (Interquartile range [IQR]: 48-60 years). Median follow-up was 68 months (IQR 21-105 months). Most patients had pT1 (23 %) or pT2 (54.1%), as well as G2 (47.5%) or G3 (23%) tumors, while lymphovascular invasion (LVI) was present in 67.1% of cases. Considering a cN1 and a cN0 groin, overall 57 out of 61 patients (93.5%) had nodal disease in the cN1 groin. Conversely, only 14 out of 61 patients (22.9%) had nodal disease in the cN0 groin. 5-year IR-free survival was 91% (Confidence interval [CI] 80%-100%) for bilateral ILND group and 88% (CI 73%-100%) for the ipsilateral ILND plus DSNB group (P-value 0.8). Conversely, 5-year CSS was 76% (CI 62%-92%) for bilateral ILND group and 78% (CI 63%-97%) for the ipsilateral ILND plus contralateral DSNB group (P-value 0.9). CONCLUSIONS: In patients with cN1 peSCC the risk of occult contralateral nodal disease is comparable to cN0 high risk peSCC and the gold standard, namely bilateral ILND, may be replaced by unilateral ILND and contralateral DSNB without affecting positive node detection, IRRs and CSS.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Penianas , Masculino , Humanos , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Pênis/patologia , Neoplasias Penianas/cirurgia , Neoplasias Penianas/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: Patients with stage II germ-cell tumours (GCT) usually undergo radiotherapy (seminoma only) or chemotherapy. Both strategies display a recognised risk of long-term side effects. We evaluated retroperitoneal lymph node dissection (RPLND) as exclusive treatment in stage II GCT. METHODS: Between 2008 and 2019 included, 66 selected stage II GCT patients underwent primary open (O-) or laparoscopic (L-)RPLND. Type of procedure and extent of dissection, operative time, node rescue, hospital stay, complications (according to Clavien-Dindo), administration of chemotherapy, relapse and site of relapse were evaluated. RESULTS: Five patients had pure testicular seminoma. Nineteen (28.8%) had raised markers prior to RPLND; 48 (72.7%), 16 (24.2%) and two (3.0%) were stage IIA, IIB and IIC, respectively. O-RPLND and unilateral L-RPLND were 36 and 30 respectively. Six stage II A patients (12.5%) had negative nodes. Four patients underwent immediate adjuvant chemotherapy. One patient was lost at follow-up. After a median follow-up of 29 months, 48 (77.4%) of the 62 patients undergoing RPLND alone remained recurrence-free; one patient had an in-field recurrence following a bilateral dissection. According to procedure, number of rescued nodes (O-RPLND: 25. IQR 21-31; L-RPLND: 20, IQR 15-26; p: 0.001), hospital stay (L-RPLND: 3 days, IQR 3-4; O-RPLND: 6 days, IQR 5-8; p: .001) and grade ≥2 complications (L-RPLND 7%, O-RPLND 22%; p: 0.1) were the only significant differences. CONCLUSION: Primary RPLND is safe in stage II GCT, including seminoma, and may warrant a cure rate greater than 70%. When feasible, L-RPLND may be as effective as O-RPLND with better tolerability.
Assuntos
Laparoscopia , Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/patologia , Neoplasias Testiculares/radioterapia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Resultado do Tratamento , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/etiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia , Estadiamento de NeoplasiasRESUMO
PURPOSE: We evaluated the oncologic efficacy of early inguinal lymph-node dissection, observation or dynamic sentinel node biopsy followed by delayed or selective inguinal lymph-node dissection in cN0 patients with penile squamous cell carcinoma. MATERIALS AND METHODS: Between 1980 and 2017 (inclusive), 296 evaluable consecutive cN0 penile squamous cell carcinoma patients underwent early inguinal lymph-node dissection (16), observation (114) or dynamic sentinel node biopsy (166). Median followup was 50 months. Tumor stage, grade, lympho-vascular invasion and age were considered. Kaplan-Meier plots illustrated 5-year inguinal relapse-free and cancer specific survival rates. Multivariable Cox regression models tested the treatment effect. Analyses were repeated after inverse probability of treatment weighting adjustment. RESULTS: The 5-year inguinal relapse-free survival and cancer specific survival rates following early, observation and dynamic sentinel node biopsy inguinal lymph-node dissection were 100%, 87%, 89%, and 84%, 81%, 85%, respectively. The 5-year crude inguinal relapse-free survival and cancer specific survival rates were 90% and 93% in low-risk patients undergoing observation. Clavien grade 3 complications were 0.6 vs 12.5% in the dynamic sentinel node biopsy and early inguinal lymph-node dissection group, respectively. After inverse probability after treatment weighting adjustment, 5-year inguinal relapse and cancer specific survival were 90% vs 73% and 90% vs 77% following dynamic sentinel node biopsy and observation, respectively. At multivariable Cox regression model, patients undergoing dynamic sentinel node biopsy had significantly lower inguinal relapse (HR 0.4, 95% CI 0.2-0.85, p 0.02) and cancer specific mortality (HR 0.29, 95% CI 0.11-0.77; p=0.01) compared to those under observation. The low number of patients undergoing early inguinal lymph-node dissection made a reliable comparison with this group impractical. CONCLUSIONS: Selective inguinal lymph-node dissection following dynamic sentinel node biopsy significantly improved inguinal relapse and cancer specific mortality when compared with observation, providing evidence of efficacy of dynamic sentinel node biopsy in clinical stage N0 squamous cell carcinoma of the penis.
Assuntos
Excisão de Linfonodo , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Biópsia de Linfonodo Sentinela , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Penianas/cirurgia , Tempo para o Tratamento , Conduta ExpectanteRESUMO
BACKGROUND: Outcomes of neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder carcinoma (MIUBC) should be improved. Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) in an open-label, single-arm, phase 2 trial (NCT01222676). PATIENTS AND METHODS: After transurethral resection of the bladder, T2-T4a N0 patients received four cycles of SGC followed by cystectomy. Sorafenib 400mg q12h daily, continuously, was added to standard GC chemotherapy. In a Simon's 2-stage design, the primary endpoint was the pathologic complete response (pT0), assuming H0: ≤0.20 and H1: ≥0.40, with a type I and type II error of 5% and 10%, respectively. RESULTS: From April 2011 to June 2016, 46 patients were enrolled. Pathologic T0 response was obtained in 20 patients (43.5%, 95% CI: 28.9-58.9); pT ≤ 1 in 25 (54.3%, 95% CI: 39.0-69.1). After a median follow-up of 35 months, the median progression-free survival was not reached (NR, interquartile range: 23.6-NR), nor was median overall survival (interquartile range: 30.3-NR). Hematologic and extrahematologic grade 3 to 4 adverse events occurred in 45.6% and 26.1% of patients, respectively. In 29 samples from responders (pT ≤ 1) and nonresponders, different distribution of missense mutations involved DNA-repair genes, RAS-RAF pathway genes, chromatin-remodeling genes, and HER-family genes. ERCC1 immunohistochemical expression was associated with pT ≤ 1 response (P = 0.047). The absence of a comparator arm prevented us to quantify sorafenib contribution. CONCLUSIONS: SGC combination was active in MIUBC, and the identified molecular features included alterations that may help personalize treatment in MIUBC with new more potent targeted agents, combined with chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Cistectomia/métodos , Desoxicitidina/análogos & derivados , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacologia , Sorafenibe , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , GencitabinaRESUMO
OBJECTIVE: To harness the frontline therapy in advanced penile squamous cell carcinoma (PSCC), for which chemotherapy exerts moderate activity but poor efficacy. Dacomitinib is an irreversible, pan-epidermal growth factor receptor (HER) inhibitor. PATIENTS AND METHODS: In a phase 2 study (NCT01728233), patients received dacomitinib 45 mg/day, orally, continuously. Inclusion criteria were SCC histology, clinical stage N2-3 or M1 (Tumour-Node-Metastasis classification system 2009), and no prior chemotherapy administration. The primary endpoint was the objective response rate (ORR, according to the Response Evaluation Criteria in Solid Tumors, version 1.1). Stopping rules based on the Bayesian posterior probability (PP) to demonstrate that the ORR exceeded 20% were set. RESULTS: From June 2013 to October 2016, 28 patients were treated. Eight (28.6%) had visceral metastases, 14 (50%) had pelvic and 17 (60.7%) clinically involved bilateral lymph nodes. One complete and eight partial responses were obtained (ORR 32.1%, 80% credibility interval 21.0-43.0%). The median (interquartile range [IQR]) follow-up duration was 19.8 (6.3-25.7) months; 12-month progression-free survival was 26.2% (95% confidence interval [CI] 13.2-51.9); 12-month overall survival (OS) was 54.9% (95% CI 36.4-82.8). The median (IQR) OS of locally advanced patients was 20 (11.1-not reached) months. The Bayesian PP of exceeding the 20% ORR target was 92.3%. Grade 3 adverse events (skin rash) were seen in three patients (10.7%). Tissue samples from 25 patients were analysed. Only two patients had high-risk human papillomavirus-positive tumours. Epidermal growth factor receptor (EGFR) amplification was found in four patients (equally responders and non-responders) and it was confirmed in all post-dacomitinib samples. Telomerase reverse transcriptase (TERT) mutations were found in responders only (60%), and phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway gene mutations were found in 42.9% of responders vs 8.3% of non-responders. CONCLUSION: Dacomitinib was active and well tolerated in patients with advanced PSCC and may represent an option when combined chemotherapy cannot be administered. Mutations in downstream effectors of EGFR signalling in relation to dacomitinib activity deserve further studies.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Penianas/tratamento farmacológico , Quinazolinonas/uso terapêutico , Administração Oral , Idoso , Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Amplificação de Genes , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Penianas/genética , Neoplasias Penianas/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Quinazolinonas/administração & dosagem , Critérios de Avaliação de Resposta em Tumores Sólidos , Transdução de Sinais/genética , Taxa de Sobrevida , Serina-Treonina Quinases TOR/metabolismo , Telomerase/genéticaRESUMO
PURPOSE: The prognosis of stage I nonseminomatous germ cell tumor of the testis is favorable. Early and late side effects of treatment may affect quality of life and survival. We determined the tolerability, safety and efficacy of laparoscopic retroperitoneal lymph node dissection in patients with stage I nonseminomatous germ cell tumor of the testis at a high volume center. MATERIALS AND METHODS: Unilateral laparoscopic retroperitoneal lymph node dissection was prospectively recorded in 225 patients from 2000 to 2014. Since 2007, patients have been treated at a multidisciplinary clinic and were proposed surgery as an alternative to surveillance or adjuvant chemotherapy. The indication for adjuvant chemotherapy changed during the study period. Descriptive statistics and regression analyses were used to evaluate the domains of safety and oncologic outcomes. RESULTS: A total of 221 patients were evaluable. Median operative time was 200 minutes. Conversion to open surgery was done in 20 cases (9%). A median of 14 nodes (IQR 11-20) was retrieved. Grade greater than 2 complications in 8 cases (3.6%) increased as the number of retrieved nodes increased. Antegrade ejaculation was maintained in 98.6% of patients. Nodal metastases were found in 29 patients (13%), of whom 7 underwent adjuvant chemotherapy. There were 14 recurrences (6.3%), including 8 of 192 (4.2%) associated with no nodal metastases and 6 of 22 (27.3%) associated with nodal metastases in patients not undergoing adjuvant chemotherapy. At regression analyses lymph node ratio was the only significant factor predictive of recurrence and of the administration of any chemotherapy (each p <0.001). Operative time, the number of retrieved nodes and conversions improved with time. CONCLUSIONS: In the context of a high volume center laparoscopic retroperitoneal lymph node dissection was safe and its oncologic efficacy was comparable to that of open surgery. Select patients with stage I nonseminomatous germ cell tumor could be offered laparoscopic retroperitoneal lymph node dissection as an alternative to other options.
Assuntos
Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/secundário , Adulto , Animais , Biópsia , Terapia Combinada , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico , Estudos Prospectivos , Espaço Retroperitoneal , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Resultado do TratamentoRESUMO
PURPOSE:: Renal cell carcinoma (RCC) is the most common tumor of the kidney. Considering the TNM classification of 2009, locally advanced and metastatic diseases are included in the groups stage III and IV. The surgical treatment of these tumors could be divided into 3 categories: (1) curative (nephrectomy and/or metastasectomy), (2) cytoreductive, and (3) palliative. Targeted agents showed impressive antitumor efficacy and prolongation of progression-free survival. The integration between target therapy and surgery in patients with locally advanced or metastatic RCC has sometimes facilitated surgery. We aimed to evaluate patients' response to tyrosine kinase inhibitor (TKI) therapy and the feasibility of surgery after that and to observe complications related to surgery. METHODS:: From February 2007 to September 2014 in the Istituto Tumori of Milan, IRCCS, we selected patients with locally advanced or metastatic diseases, treated with target therapy before surgery (which comprised nephrectomy or partial nephrectomy, cytoreductive surgery, and metastasectomy) and cryoablation. RESULTS:: We selected 33 patients who underwent surgery after TKI therapy. As for response to TKIs, 20 patients (60%) had stable disease, 9 patients (28%) had a partial response, and 4 patients (12%) had progressive disease. A total of 17 patients (51%) presented complications directly or indirectly related to surgery and most of those were classified as grade II Clavien-Dindo score. CONCLUSIONS:: The association between TKI and surgery seems to have no contraindications. Our dataset provides an example of how surgery after TKI is possible in locally advanced metastatic tumor and does not have an excessive rate of postoperative complications.
Assuntos
Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Renais/cirurgia , Metastasectomia/métodos , Nefrectomia/métodos , Complicações Pós-Operatórias , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Limited information is available regarding the use of androgen receptor (AR) immunohistochemical expression in muscle-invasive or metastatic urothelial carcinoma. We aimed to evaluate the frequency of AR expression by tumor cells (TC), its prognostic role, and its relationship with programmed cell-death ligand 1 (PD-L1) expression in these patients. PATIENTS AND METHODS: From September 2015 to January 2017, we collected tissue from patients who received platinum-based chemotherapy at our center. Immunohistochemistry for AR was performed (1% cutoff of TC). PD-L1 coexpression, by TC or immune cells (1% cutoff), was also analyzed. Molecular analysis of AR gene was performed by sequencing of exons 5 to 8 and by fluorescence in-situ hybridization analysis. Cox models for overall survival (OS), adjusted for stage, visceral metastases, and platinum type, were fitted. RESULTS: A total of 110 patients had tumor samples stained. Overall, 48 (43.6%) had AR-expressing TC: 19 (17.3%) had 1%-5% expression, 15 (13.6%) 5%-25% expression, and 14 (12.7%) > 25% expression. Among the latter, 7 had molecularly evaluated tumor tissue: no AR gene mutations or amplifications were found, but polysomy of Xq chromosome was seen. PD-L1 expression by TC and immunohistochemistry concordantly decreased with increasing levels of AR expression by TC. In Cox analyses, AR expression was not associated with OS, both on univariable (P = .477) and multivariable (P = .505) analyses. CONCLUSION: AR is frequently expressed in patients with muscle-invasive and advanced urothelial carcinoma, and it does not seem to be prognostic for OS. The AR pathway is worthy of clinical studies to assess its synergistic action with anti-PD-L1 therapy.
Assuntos
Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/tratamento farmacológico , Platina/uso terapêutico , Receptores Androgênicos/metabolismo , Neoplasias Urológicas/tratamento farmacológico , Idoso , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Cromossomos Humanos X/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Androgênicos/genética , Estudos Retrospectivos , Análise de Sequência de DNA , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/genética , Neoplasias Urológicas/metabolismoRESUMO
BACKGROUND: Different approaches have been described in published studies for carcinoma in situ (CIS) of the glans penis (erythroplasia of Queyrat), including topical chemotherapy or immunotherapy and laser or surgical excision. We evaluated the efficacy of topical imiquimod (IQ) followed by carbon dioxide laser ablation of the lesion. PATIENTS AND METHODS: From 2010 to 2015, 10 patients affected by CIS of the glans were treated by IQ, followed by carbon dioxide laser ablation. For every patient, we performed histologic examination before and after IQ. Local toxicity and adverse effects were recorded. RESULTS: After treatment, histologic examination showed no residual tumor in 6 patients (complete response [CR]), stable disease in 2 patients, and progressive disease in 2 patients. Those with a CR had human papillomavirus-related lesions, and they had no experienced relapses after a mean follow-up of 26 months. The 2 patients with progressive disease underwent total penectomy. All patients were alive at the last follow-up examination. All patients experienced a mild local toxicity (burning erythema) but no major adverse effects. CONCLUSION: Local treatment with IQ for glans CIS is effective mainly for human papillomavirus-related lesions. The present study is the first to record the histologic examination findings before and after IQ treatment. The small number of patients, owing to the rarity of this disease, was the main limitation of the present study. IQ must be used carefully, and a close follow-up protocol is mandatory because of the lack of long-term efficacy data.
Assuntos
Aminoquinolinas/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma in Situ/terapia , Lasers de Gás/uso terapêutico , Neoplasias Penianas/terapia , Administração Tópica , Adulto , Idoso , Aminoquinolinas/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma in Situ/virologia , Intervalo Livre de Doença , Humanos , Imiquimode , Lasers de Gás/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/terapia , Neoplasias Penianas/virologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To retrospectively analyze the efficacy and safety results of the combination of methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO) regimen for patients with human chorionic gonadotropin (HCG)-producing germ cell tumors and who had failed multiple courses of chemotherapy. METHODS: Patients who had failed at least 2 regimens received methotrexate 100 mg/m, followed by methotrexate 200 mg/m over 12 hours day 1, etoposide 100 mg/m and dactinomycin 0.5 mg days 1 and 2, folinic acid 25 mg orally every 6 hours days 2 and 3, alternating with cyclophosphamide 600 mg/m plus vincristine 1 mg/m day 8, every 21 days. Treatment was continued until marker normalization and for additional 2 cycles. Response rate, progression-free (PFS), and overall survival (OS) were the efficacy endpoints. Cox regression analyses examined the prognostic impact of candidate factors on PFS and OS. RESULTS: From February 92 to May 13, 41 patients were treated in third line (n=20, 49%) or beyond (n=21, 51%). Seventeen (41%) had received high-dose chemotherapy. Thirty-one patients (75.6%) had a response with marker reduction, including 4 complete (9.8%) and 5 (12.2%) partial responses with HCG normalization. Median PFS was 3 months (95% confidence interval [CI], 2-4) and median OS was 8 months (95% CI, 6-10). Most frequent grade 3-4 toxicity was hematologic (20 patients, 48.8%). One toxic death (cerebral hemorrhage) occurred. On multivariable analysis, the line of treatment (greater than third vs. third) was the only significant predictor of both PFS (hazard ratio: 2.50, 95% CI, 1.20-5.24, P=0.015) and OS (hazard ratio: 3.17, 95% CI: 1.46-6.89, P=0.004). CONCLUSIONS: EMACO is an attractive regimen with acceptable toxicity and could be considered an option for HCG-expressing germ cell tumors whenever multiple relapses occur.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Gonadotropina Coriônica/biossíntese , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/uso terapêutico , Humanos , Masculino , Metotrexato/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/metabolismo , Estudos Retrospectivos , Neoplasias Testiculares/metabolismo , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Residual retroperitoneal masses in NSGCT need postchemotherapy retroperitoneal lymph-node dissection (PC-RPLND). Open (O) PC-RPLND is a standardized procedure, but morbidity is not negligible and mostly attributable to laparotomy. Laparoscopic (L) PC-RPLND may improve tolerability profile. We evaluated viability, toxicity, and short to medium-term oncologic outcome of L-PC-RPLND following well-defined selection criteria. PATIENTS AND METHODS: Since February 2011, consecutive patients with a unilateral residual mass (≥1 cm or growing), normalized markers, and limited encasement of inferior vena cava and/or aorta were candidate to unilateral L-PC-RPLND. Surgical performances, histology, hospital stay, complications within 30 days, and survival were recorded. Patients were regularly followed up. Adjuvant chemotherapy was not provided. RESULTS: Sixty-seven patients (stage IIA = 14; IIB = 41; IIC = 7; III = 5), representing 29% of all those candidate to PC-RPLND in this time frame, underwent L-PC-RPLND up to August 2015. Median size of the mass was 27 mm (interquartile range [IQR] 15-31). Median operative time was 234 minutes (IQR 184-250). Three procedures were converted to open surgery. Mean hospital stay was 3 days (IQR 2-4). Out of three (4.5%), one grade III (lymphocele requiring drainage) complication occurred. Sixty-six (98.5%) patients maintained antegrade ejaculation. Histology revealed teratoma in 76%, fibronecrotic tissue in 21%, and viable cancer in 3% patients. All patients are alive and event free after a median follow-up of 21 months (IQR 10-30). CONCLUSIONS: In a referral center, L-PC-RPLND is a transferable option for a proportion of patients with a residual mass. Tolerability is acceptable, and current oncologic outcome is consistent with a safe oncologic profile.
Assuntos
Laparoscopia/métodos , Excisão de Linfonodo/métodos , Linfocele/cirurgia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Espaço Retroperitoneal/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Adolescente , Adulto , Quimioterapia Adjuvante , Bases de Dados Factuais , Estudos de Viabilidade , Seguimentos , Humanos , Laparotomia , Tempo de Internação , Linfocele/etiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Little is known about the outcomes and prognostic factors of adjuvant chemotherapy for locally advanced penile squamous cell carcinoma after regional lymphadenectomy (LAD). PATIENTS AND METHODS: We retrospectively reviewed the data from 21 patients who had received taxane, cisplatin, and 5-fluorouracil (TPF, every 3 weeks) in the adjuvant setting at our center. Univariable and multivariable Cox regression analyses were undertaken for disease-free (DFS) and overall survival (OS) of TPF. RESULTS: The patients had received TPF from July 2004 to July 2012 after inguinal (n = 6) or inguinal plus pelvic LAD (n = 15), and the median follow-up was 52 months. Thirteen (61.9%) had pelvic and 5 (23.8%) bilateral inguinal nodal metastases. The median time from LAD to the start of TPF was 5.4 weeks (interquartile range [IQR], 4.1-7.3 weeks). Metastatic tumor tissue from 11 of 19 evaluable patients (57.9%) showed positive immunohistochemistry staining for p53. Univariably, only the expression of p53 showed a trend toward poorer DFS (hazard ratio [HR], 4.14; 95% confidence interval [CI], 0.87-19.68; P = .074) and OS (HR, 4.54; 95% CI, 0.95-21.56; P = .056). The same results were obtained multivariably for DFS (HR, 3.76; 95% CI, 0.78-17.96; P = .096) and OS (HR, 4.29; 95% CI, 0.89-20.57; P = .067). The median DFS was 8.9 months (IQR, 5.9-22.7 months) for p53-expressing patients versus not estimable for non-p53-expressing patients (P = .051) and the median OS was 17.2 months (IQR, 12.8-22.7 months) and not estimable, respectively (P = .037). CONCLUSION: In patients who had received adjuvant TPF for node-positive penile squamous cell carcinoma, p53 IHC expression seemed to be associated with a poorer outcome, and further study is warranted in larger data sets to confirm these findings. This information might be useful to improve the prognostic allocation.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Neoplasias Penianas/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/metabolismo , Cisplatino/uso terapêutico , Esquema de Medicação , Fluoruracila/uso terapêutico , Humanos , Canal Inguinal , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Pelve , Neoplasias Penianas/metabolismo , Prognóstico , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: The role of chemotherapy in nodal metastases from penile squamous cell carcinoma is not defined. We evaluated the efficacy of a combination of T-PF (a taxane, cisplatin, and 5-fluorouracil) in neoadjuvant and adjuvant settings. PATIENTS AND METHODS: Since June of 2004, T-PF was administered to stage N2 to 3 patients. With time, neoadjuvant chemotherapy administration prevailed with respect to use in the adjuvant setting. Primary end points were progression-free (PFS) and overall (OS) survival. Secondary objectives were tolerability and activity in the neoadjuvant setting. Nonparametric tests, Kaplan-Meier, and regression analyses were performed. RESULTS: As of October of 2012, 47 consecutive N2 to 3 M0 patients had undergone neoadjuvant (n = 28) or adjuvant (n = 19) T-PF: 18 patients (38.3%) remain disease-free after a median follow-up of 22 months (interquartile range, 17-42 months). The 2-year disease-free survivals were 36.8% (95% confidence interval [CI], 15.2-58.5) versus 7.1% (95% CI, 0-16.7) after adjuvant and neoadjuvant therapy, respectively. N3 metastases were associated with a poorer PFS, and bilateral metastases and mutated p53 were associated with a poorer OS. After neoadjuvant treatment, 43% clinical responses and 14% complete pathologic remissions were recorded, but responses were not associated with survival. Neutropenia (25.5%) was the most frequent Grade ≥ 2 toxicity. CONCLUSION: The T-PF regimen is well tolerated and compares with other regimens in terms of activity and efficacy in the neoadjuvant setting, and very long survivals have been recorded after adjuvant administration. The role of perioperative treatment in these patients remains controversial. Some caution in administering preemptive treatment in patients with resectable disease is needed.
Assuntos
Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Excisão de Linfonodo/métodos , Neoplasias Penianas/terapia , Taxoides/administração & dosagem , Adulto , Idoso , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
AIMS AND BACKGROUND: To evaluate postoperative pain (PoP) and quality of life (QoL) in patients undergoing open (O-) or laparoscopic (L-) retroperitoneal lymph node dissection (RPLND) for clinical stage I (CS I) and normal markers CS IIA nonseminomatous germ cell tumors. METHODS: Since March 2010, a prospective nonrandomized trial evaluated dynamic and rest (R) numeric pain scale (NPS) following patient-controlled analgesia and baseline (T0), 3-month (T3), and 6-month (T6) QoL status assessed by Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and the Italian-validated Functional Assessment of Chronic Illness Therapy (FACT-T-SG) at T6. Secondary endpoints included length of hospital stay (LHS), interval to recovery (ItR), complications, and oncologic outcomes. RESULTS: In March 2012, 69 (64 CS I) patients were enrolled. Five patients only chose O-RPLND. The PoP and complete QoL data are available in 41 and 56 patients, respectively. The R-NPS significantly improved in days 1-2 vs day 0 (p<0.0008). The FACT-G scores improved from baseline: the emotional well-being scale was the most relevant at T3 (+7.0, p = 0.0001) and T6 (+6.9, p = 0.0002). The FACT-TS-G indicated high satisfaction levels. Median LHS and ItR were 3 and 15 days. Six complications required an intervention. Nodal metastases were found in 14 (20.3%) patients. Following a median follow-up of 36 months, 6 (8.9%) patients relapsed (2/12 among pN+), and 8 patients (11.9%) underwent chemotherapy. All patients maintained antegrade ejaculation and are alive and disease-free. CONCLUSIONS: Almost all patients chose L-RPLND, which is associated with a rapid improvement of postoperative pain; QoL scores improved up to 6 months. The L-RPLND may be considered as an alternative only when performed in highly experienced centers.
Assuntos
Laparoscopia , Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Manejo da Dor , Dor Pós-Operatória/terapia , Qualidade de Vida , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Idoso , Humanos , Excisão de Linfonodo/efeitos adversos , Linfocele/etiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Espaço RetroperitonealRESUMO
OBJECTIVES: Approximately one-third of the metastatic germ cell tumors (GCT) in patients are classified as intermediate-risk metastatic GCT, and available guidelines recommend the same treatment of poor-risk cases. Yet the prognosis of these patients is heterogeneous, and consequently refining the intensity of treatment is warranted. We aimed to address the heterogeneity of this category by providing a proof of principle for reclassification attempt. PATIENTS AND METHODS: Data on consecutive patients with intermediate-risk metastatic GCT and who received treatment at Fondazione INT Milano in the time frame between February 1980 and March 2014 were collected. Cox regression analyses were done, evaluating potential prognostic factors for overall survival (OS, primary end point) to first-line therapy. Each factor was evaluated in a multivariable model. Recursive partitioning was performed to define prognostic risk groups. RESULTS: A total of 224 patients were suitable for the present analysis. Median age was 26 years (interquartile range: 22-31), 11 patients (4.9%) had a retroperitoneal primary tumor, 6 yielded seminomatous histology, 85 (37.9%) had lung metastases, and 58 (25.9%) had bulky (i.e.,≥ 10 cm) retroperitoneal lymph nodes. Patients received cisplatin, bleomycin, and etoposide (PEB, n = 199) or vinblastine (PVB, n = 23); however, 2 patients received other treatments. Median follow-up was 135 months (interquartile range: 81-223). Globally, 5-year progression-free survival and OS rates were 72.8% (95% CI: 67.1-79.0) and 86.2% (81.7-91.0), respectively. In the multivariable model for OS, elevated alfa fetoprotein (AFP) level was the only significant prognostic factor (hazard ratio = 1.48, 95% CI: 1.12-1.96). The 2 separate prognostic groups with differential OS outcomes were identified based on the cutoff level of 6,200 IU/ml. The 10-year OS rate was 55.6% (95% CI: 36.6-84.3), and it was 86.7% (95% CI: 82.0-91.7) for those with AFP levels more than (n = 19, 8.5%) and less than (n = 205, 91.5%) the cutoff, respectively. CONCLUSIONS: A small fraction of patients with highly elevated AFP levels have an OS approximating the poor prognostic category, whereas most of them are close to good-risk cases. This might have implications to select outlier patients for clinical trials and molecular characterization.
Assuntos
Neoplasias Embrionárias de Células Germinativas/classificação , Neoplasias Retroperitoneais/classificação , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/mortalidade , Estudos Retrospectivos , Adulto Jovem , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Survival estimates with first-line treatment for patients with metastatic poor prognosis germ cell tumors (GCT) are still suboptimal in the literature. We conducted a retrospective study to evaluate the outcome of patients referred to our tertiary cancer center. PATIENTS AND METHODS: A retrospective analysis was conducted on patients who received at least first-line chemotherapy at our center. Distribution of clinical characteristics was evaluated in the periods < 1997, 1997 to 2001, 2001 to 2006, and 2007 to 2013. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariable and multivariable Cox models with prespecified clinical variables were undertaken for PFS and OS. All tests and confidence intervals were 2-sided and set at a P = .05 level of significance. RESULTS: Between 1982 and 2013, 168 patients were identified. The median age was 27 years (interquartile range [IQR], 22-34). The presence of liver, bone, or brain metastases trended to greater incidence from 1997 onward (27.5% < 1997 to 55.6% in 2007-2013; χ(2)P = .054). Median follow-up was 102 (IQR, 63-166) months. Global 5-year PFS was 48.5% (95% confidence interval [CI], 41.5-56.8) and OS was 63.2% (95% CI, 56.0-71.2). In multivariable analysis, treatment period was not significantly associated with either PFS (overall P = .229) or OS (overall P = .216). CONCLUSION: In this single-center series of consecutive poor prognosis GCT we could observe greater PFS and OS than the historical estimates. This observation was independent from the period of treatment. Based on the present results, studies focused on improving the outcome in the sole poor-risk cohort should be discouraged. Results were biased by their retrospective quality.
Assuntos
Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Testiculares/mortalidade , Adulto , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico , Modelos de Riscos Proporcionais , Encaminhamento e Consulta , Estudos Retrospectivos , Terapia de Salvação , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To assess the clinical outcome of testicular sex cord stromal tumors (TSCST) according to management and stage. PATIENTS AND METHODS: Clinical and pathologic features, stage, and treatment of patients with TSCST were retrieved from our database. The Kaplan-Meier method estimated the relapse-free survival and cancer-specific survival. RESULTS: We identified 67 patients between December 1982 and January 2013: 55 patients (82.1%) had a Leydig cell tumor and 11 patients (16.4%) had a Sertoli cell tumor. Four patients (5.9%) presented with gynecomastia. Forty-eight patients (71.6%) had no pathologic risk factor, and patients 3 had ≥3 risk factors. Testis-sparing surgery was performed in 31 patients (46.3%) and orchiectomy in 36 patients (53.7%). The median tumor diameter was 0.7 cm (interquartile range, 0.6-1.3) and 1.5 cm (interquartile range, 0.9-2.6) in the 2 groups, respectively (P, .007 at Mann-Whitney rank-sum test). The 5-year relapse-free survival was 89.4% (95% confidence interval, 75.9%-95.5%) and cancer-specific survival was 90.3% (95% confidence interval, 72.7%-96.7%), respectively. Metastases were documented in 8 patients (11.9%), 5 relapsing after a median follow-up of 37.4 months. All 3 patients with ≥3 risk factors had metastatic disease. Four of 5 patients with retroperitoneal metastases only were cured by retroperitoneal lymph node dissection (3 patients at presentation and 1 during follow-up); 4 patients undergoing chemotherapy progressed and ultimately died of disease. CONCLUSION: Most of the patients with TSCST had a favorable prognosis. Testis-sparing surgery may be feasible and effective in case of small tumors. Few patients had metastatic spread, but only those with nodal metastases may benefit from an early retroperitoneal lymph node dissection. Risk factors associate with disease behavior, but indications to prophylactic intervention remain controversial.
Assuntos
Orquiectomia , Tratamentos com Preservação do Órgão , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Neoplasias Testiculares/cirurgia , Adulto , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Tumores do Estroma Gonadal e dos Cordões Sexuais/mortalidade , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Taxa de Sobrevida , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the first Italian study, we collected cases of teratoma, alongside the protocol for malignant germ cell tumors. PROCEDURE: Patients with teratoma were collected from 2004 to 2014. Teratomas were classified according to the WHO classifications, as mature and immature. Patients with pathological aFP and/or bHCG, and those with a malignant germ cell component were not included. RESULTS: The study enrolled 219 patients (150 mature, 69 immature teratomas) with a median age at diagnosis of 42 months. The primary sites involved were: 118 gonadal and 101 extragonadal teratomas. Two females with ovarian teratoma had a positive family history. Complete and incomplete surgeries were performed in 85% and 9% of cases. Seventeen events occurred: six females had a second metachronous tumor (5 contralateral ovarian teratoma, 1 adrenal neuroblastoma) and 11 teratomas relapsed/progressed (3 mature, 8 immature teratomas). Two patients died, one of progressive immature teratoma and one of surgical complications. At a median follow up of 68 months, the event-free, relapse-free, and overall survival rates were 90.6%, 94.3%, 98.6%, respectively. CONCLUSIONS: Teratomas show a good prognosis, especially the mature ones: surgery and follow-up remain the standard approach. Incomplete surgery in immature teratoma is the group at greatest risk of relapse. Bilateral ovarian tumors are a possibility, and the rare family predisposition to ovarian mature teratoma warrants further analyses.
Assuntos
Recidiva Local de Neoplasia/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neuroblastoma/epidemiologia , Neoplasias Ovarianas/epidemiologia , Teratoma/epidemiologia , Neoplasias Testiculares/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Teratoma/mortalidade , Teratoma/patologia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto JovemRESUMO
BACKGROUND: Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis. PATIENTS AND METHODS: Between the years 1985 and 2012, 86 patients with PMGCT were treated at our center. Cox proportional hazards regression analysis was conducted in the population of nonseminomas to examine the prognostic effect of candidate factors on progression-free and OS. OS curves were compared using the Kaplan-Meier method and the log-rank test. RESULTS: Mean age was 29.8 years (range, 15-63 years). Twenty-five patients (29.1%) had lung and 8 (9.3%) liver, bone, or brain metastases. Twelve patients (13.9%) received upfront high-dose chemotherapy and 45 patients (52.3%) underwent surgery after chemotherapy. Cox analyses included 61 evaluable primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs). The final model of factors indicating a poor prognosis included the combination of surgery and histological response (overall P = .011) and lung metastases (hazard ratio, 3.03; 95% confidence interval, 1.12-8.15; P = .028). The model showed a bootstrap-corrected Harrel c-statistic for OS of 0.66. A risk stratification model based on the combination of these factors and accounting for a 50% 5-year survival cutoff identified 2 groups (poor prognosis, n = 33 vs. good prognosis, n = 28) with distinct OS curves (P < .001). Preoperative serum tumor marker level was not associated with the final histology (P = .853, χ(2) test). Results were limited by small numbers. CONCLUSION: Patients with PMNSGCT included 2 subpopulations with distinct prognosis, and therapeutic improvements are needed for patients with poor-risk features.