Search PubMed⌕ Search

Biomedical subjects

Giuseppe Di Lorenzo

Publications and source records attributed to Giuseppe Di Lorenzo.

At least 19 recordsLinked to original sources
PubMed2026

Trastuzumab Deruxtecan in Metastatic Urothelial Carcinoma with NGS-Detected ERBB2 Amplification: A Four-Patient Real-World Case Series.

Background: Next-generation sequencing (NGS)-detected ERBB2 amplification occurs in a subset of urothelial carcinomas, but its role as a treatment-selection marker for trastuzumab deruxtecan (T-DXd) remains uncertain. Methods: We retrospectively reviewed four patients with metastatic urothelial carcinoma treated with T-DXd in routine practice from 2024. Treatment selection was based on NGS-detected ERBB2 amplification because HER2 immunohistochemistry and in situ hybridization were unavailable. Results: Four men aged 65-76 years received T-DXd: one in the second line and three in the fourth or fifth line. The best radiological responses, abstracted from contemporaneous radiology reports and oncology medical records, were complete response in one patient, partial response in one, and stable disease in two. Three patients had previously received enfortumab vedotin. Documented adverse events included fatigue, anemia, diarrhea, rash, and leukopenia. No interstitial lung disease or pneumonitis was documented in the available records. Conclusions: These observations are descriptive and hypothesis-generating. They do not establish the efficacy or safety of T-DXd or validate ERBB2 amplification as a predictive biomarker, but they support prospective evaluation of genomic ERBB2 amplification when standard HER2 testing is unavailable.

Humans↗
PubMed2025

The Role of Homologous Recombination Deficiency (HRD) in Renal Cell Carcinoma (RCC): Biology, Biomarkers, and Therapeutic Opportunities.

Renal Cell Carcinoma (RCC) is a common malignancy, often diagnosed incidentally. In recent years, the prognosis of metastatic disease has been improved due to the development of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) as first-line treatments. However, when progression occurs, the therapeutic options are limited. Understanding crucial biological pathways could lead to a greater understanding of the natural history of the disease, which could help to overcome the mechanism of resistance and to develop new treatments. The clinical significance of homologous recombination deficiency (HRD) in RCC remains to be investigated. To improve the knowledge about this topic, we conducted a narrative review to summarize the current evidence on HRD-related variations and signatures in RCC, together with their prognostic and predictive implications. Preliminary evidence indicates that canonical HRD variants (BRCA1/2) are infrequent in RCC, while broader DNA damage response (DDR) alterations like BAP1, PBRM1, ATM, and SETD2 are more prevalent. Elevated HRD genomic scores in clear-cell RCC correlate with a worse prognosis and an immunologically exhausted microenvironment. From a therapeutic point of view, PARP inhibitor monotherapy has exhibited initial efficacy in small cohorts with high levels of DDR mutation, yet remains investigational for RCC.

Humans↗
PubMed2006

Are abstracts presented at the EAU meeting followed by publication in peer-reviewed journals? A critical analysis.

PURPOSE: Our goal was to assess the rate and time-course of peer-reviewed publication of abstracts presented at the European Association of Urology (EAU) Annual Meeting and to identify factors predictive of publication. METHODS: All abstracts accepted for presentation at the 2000 and 2001 EAU annual meetings were identified from the related published supplements in European Urology. The subsequent publication rate was estimated for the corresponding studies based on a scan of Medline covering a 5-year period following the meetings. We examined whether the following factors were associated with publication rate: research type, study subject, and country of origin. The analysis was performed using logistic regression of the dichotomous variable of publication versus non-publication and the candidate factors. RESULTS: Overall, 47.3% of 1406 abstracts presented at the EAU meetings were followed by publication in peer-reviewed journals. Pre-clinical research studies were more likely to be published than clinical studies (53.3% vs 45%, p<0.05). Prospective series were more likely to be published than retrospective ones (46.5% vs 32.2%, p<0.05). Studies presented at the meetings were mostly from Europe (74.2%). Mean time to publication was 8.6 months, and in most cases, the reports were published in The Journal of Urology and European Urology. The mean IF of journals where papers were published was 1.95. CONCLUSIONS: Almost half of the abstracts presented at the EAU are ultimately published in peer-reviewed journals, usually within 2 years after presentation. The publication rate differs significantly according to country of origin, study subject, and research type.

Abstracting and Indexing↗
PubMed2006

Medical expulsive treatment of distal-ureteral stones using tamsulosin: a single-center experience.

PURPOSE: To evaluate the efficacy of the addition of tamsulosin to our standard expulsive pharmacologic therapy for the treatment of distal-ureteral stones. PATIENTS AND METHODS: A series of 96 patients referred to our department for the management of symptomatic distal-ureteral calculi were randomly divided into group 1 (N = 46) who received diclofenac (100 mg/daily) plus aescin (80 mg/daily) and group 2 (N = 50) who received the same therapy plus tamsulosin (0.4 mg/daily) for a maximum of 2 weeks. There were no differences between the groups with respect to age, sex, or stone size. The primary endpoint was the expulsion rate. Expulsion time, need for analgesics, need for hospitalization, and drug side effects were the secondary endpoints. RESULTS: The expulsion rate was significantly higher in group 2 (90%) than in group 1 (58.7%; P = 0.01), and group 2 achieved stone passage in a shorter time (mean 4.4 v 7.5 days, respectively; P = 0.005). Lower analgesic use was found in group 2 (P = 0.003), as well as significantly fewer hospitalizations for recurrent colic (P = 0.01). Both groups experienced few side effects associated with expulsive therapy. CONCLUSIONS: A conservative approach should be considered as an option in the management of uncomplicated distal-ureteral stones. Even if the best pharmacologic expulsive regimen remains to be established, the use of the selective alpha-blocker tamsulosin is recommended in this setting.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

The use of tamsulosin in the medical treatment of ureteral calculi: where do we stand?

It has recently been demonstrated that specific adrenoceptors subtypes (alpha(1A)/alpha(1D)) are prevalent in the distal part of the ureter, a finding supporting the interesting results obtained by different groups with the use of tamsulosin in the treatment of distal ureteral calculi. We performed a prospective randomized study to evaluate the effects of the addition of tamsulosin on our standard pharmacological therapy for the treatment of selected ureteral stones. A total of 64 patients referred to our department for the management of symptomatic ureteral calculi were considered. Patients were randomly divided into two treatment groups: group A (n=32) who received diclofenac (100 mg/daily) plus aescin (80 mg/daily) and group B (n=32) who received the same therapy plus tamsulosin (0.4 mg/daily) for a maximum of 2 weeks. No significant differences were found between the groups for age, gender distribution and mean stone size measured in the single largest dimension at presentation. The stone expulsion rate was 60% (19/32 patients) for group A and 88% for (28/32) for group B with a mean expulsion time of 7.4+/-2.2 (range 3.5-12) and 4.8+/-2.7 days (range 1.8-10.5), respectively. Group B showed a significant advantage in terms of both expulsion rate (P=0.01) and expulsion time (P=0.005). Different analgesics from those used in the standard treatment regimen were required in ten patients in group A (31%) but only three patients in group B (9%). This difference was significant (P=0.003). Hospitalization for recurrent colic was needed in 21% of patients in group A (7/32) and in 9% in group B (3/32) (P=0.01). Only two patients in each group (6%) experienced minor side effects associated with the expulsive therapy. Our data confirm the efficacy of tamsulosin in the treatment of distal ureteral stones up to 1 cm. This selective alpha-blocker should therefore be included in the pharmacological regimen of patients when a conservative approach is considered in the treatment of ureteral lithiasis.

Adrenergic alpha-Antagonists↗
PubMed2005

Prospective clinical trials of biotherapies in solid tumors: a 5-year survey.

PURPOSE: To review the content and quality of prospective clinical trials of biotherapies in solid tumors. METHODS: Data were collected from the literature between 1990 and 2002 on general study characteristics, patient and disease factors, study methodology, and factors related to completeness of reporting. Quality of phase II studies was evaluated by an ad hoc questionnaire. Descriptive statistics, contingency tables, and the chi-square test were applied. RESULTS: A total of 334 studies were selected, of which about three quarters were multicenter, with 42.5% reporting phase I, 42.2% phase II or I/II, and 11.9% phase III or II/III studies. Only 13.7% were randomized, and a study design emphasizing statistical analysis was lacking in as many as one third. The assessment of biological endpoints was stated as the primary or secondary goal in half of these studies. Melanoma (17.1%), renal carcinoma (11.1%), gastrointestinal neoplasms (11.1%), and lymphomas (6.3%) were the most studied diseases. Immunotherapies accounted for 182 studies; the remaining 152 reported other biotherapies. Patients with (1) advanced disease (P = 0.003), (2) heavily pretreated neoplasms (P < 0.0001), (3) poor performance status (PS < 2) (P < 0.0001), were more frequently enrolled in studies of biotherapy. Biotherapies were less frequently evaluated in phase III studies (7/152) compared with immunotherapies (33/182) (P < 0.0001). A statistical study design was more frequently identified in biotherapy trials (127/152) compared with immunotherapy trials (98/182) (P < 0.0001). Biological endpoints were less frequently evaluated in phase III studies in both biotherapies (100% no vs 0% yes) and immunotherapies (81.8% no vs 18.2% yes) (P = 0.01, for biotherapies; P < 0.0001, for immunotherapies). Phase I immunotherapy studies more frequently applied biological or molecular criteria for patient selection (41.1%) than phase II (29.3%) and III (3.1%) studies (P < 0.0001). CONCLUSIONS: The very wide diversity in modalities of conducting and reporting clinical trials of biotherapies of solid tumors and the presence of some methodological pitfalls suggest that the methodological standards for conducting and publishing clinical trials in biotherapies should be improved to enhance the reliability of the body of published data.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Dynamic sentinel node biopsy in clinically node-negative penile cancer versus radical inguinal lymphadenectomy: a comparative study.

OBJECTIVES: To evaluate the reliability and morbidity of dynamic sentinel node biopsy compared with radical inguinal lymphadenectomy (RIL) in the treatment of selected patients with squamous cell penile carcinoma. METHODS: We retrospectively considered patients with clinically node-negative Stage pT2-pT3 penile cancer. From 1994 to 2000, 48 patients (group 1, mean age 63 years) underwent penectomy and, after 4 weeks, prophylactic bilateral RIL. From 2001 to 2004, 22 patients (group 2, mean age 67 years) underwent penectomy and dynamic sentinel node biopsy. After 4 weeks, bilateral RIL was performed. RESULTS: In group 1, nodal disease was found in 39.6% of the patients. Early complications occurred in 21 patients (47.5%), with the most common being seroma formation. Late complications occurred in 18 patients (37.5%), with the most common being leg edema. In group 2, preoperative lymphoscintigraphy revealed no sentinel nodes in 1 patient, unilateral sentinel nodes in 7, and bilateral nodes in 14. A total of 35 sentinel nodes were seen in 42 inguinal regions (mean 0.83), including 27 (77.2%) identified with the probe and blue dye and 8 (22.8%) located with the probe only. Metastases were noted in 8 (36.4%) of 22 patients, bilaterally in 4 of them. Early minor complications occurred in 3 patients (13.6%). The technique had an 89% negative predictive value and 90% sensitivity. CONCLUSIONS: The results of this study have shown that dynamic sentinel node biopsy is a minimally invasive technique that is easy to perform, with similar results to those of RIL, but lower morbidity. This procedure offers the possibility of less-extensive surgery for clinically node-negative penile carcinoma.

Carcinoma, Squamous Cell↗
PubMed2005

Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial.

BACKGROUND: Gynaecomastia and breast pain are frequent adverse events with bicalutamide monotherapy, and might cause some patients to withdraw from treatment. We aimed to compare tamoxifen with radiotherapy for prevention and treatment of gynaecomastia, breast pain, or both during bicalutamide monotherapy for prostate cancer. METHODS: 51 patients were randomly assigned to 150 mg bicalutamide per day, 50 patients to 150 mg bicalutamide per day and to 10 mg tamoxifen per day for 24 weeks, and 50 patients to 150 mg bicalutamide per day and radiotherapy (one 12-Gy fraction on the day of starting bicalutamide). 35 of the 51 patients allocated bicalutamide alone developed gynaecomastia or breast pain and were subsequently randomly allocated to tamoxifen (n=17) or radiotherapy (n=18) soon after symptoms started (median 180 days, range 160-195). Gynaecomastia and breast pain were assessed once a month. Severity of gynaecomastia was scored on the basis of the largest diameter. Breast pain was scored as none, mild, moderate, or severe. The primary outcome was frequency of gynaecomastia or breast pain; secondary outcomes were safety and tolerability, relapse-free survival, as assessed by concentration of prostate specific antigen, and quality of life. Analyses were by intention to treat. RESULTS: 35 of 51 patients assigned bicalutamide alone developed gynaecomastia, compared with four of 50 assigned bicalutamide and tamoxifen (odds ratio [OR] 0.1 [95% CI 0.08-0.12], p=0.0009), and with 17 of 50 assigned bicalutamide and radiotherapy (0.51 [0.47-0.54], p=0.008). Breast pain was seen in 29 of 51 patients allocated bicalutamide alone, compared with three allocated bicalutamide and tamoxifen (0.1 [0.07-0.11], p=0.009), and with 15 allocated bicalutamide and radiotherapy (0.43 [0.40-0.45], p=0.02) In 35 patients assigned bicalutamide alone who subsequently developed gynaecomastia, breast pain, or both, tamoxifen significantly reduced the frequency of gynaecomastia (0.2 [0.18-0.22], p=0.02). INTERPRETATION: Antioestrogen treatment with tamoxifen could help patients with prostate cancer to tolerate the hypergonadotropic effects of bicalutamide monotherapy.

Aged↗
PubMed2005

Management of gynaecomastia in patients with prostate cancer: a systematic review.

Patients with prostate cancer are increasingly being offered treatment with non-steroidal antiandrogen monotherapy, which offers potential quality-of-life benefits compared with other treatment. Non-steroidal antiandrogens directly antagonise androgen action in breast tissue, and indirectly increase the oestrogen concentration. Thus, the most troublesome side-effects of monotherapy with these drugs are gynaecomastia and breast pain. Patients younger than 60 years of age, who might not have symptoms of prostate cancer, are probably more concerned about their body image and the development of enlarged breasts than are those older than 60 years. Clinicians who seek a treatment for prostate cancer need information on simple and well-tolerated options for the management of gynaecomastia and breast pain. In this review, management options for gynaecomastia caused by hormonal manipulation in patients with prostate cancer are discussed.

Androgen Antagonists↗
PubMed2005

How to decrease pain during transrectal ultrasound guided prostate biopsy: a look at the literature.

PURPOSE: There is growing interest among urologists on the need for decreasing pain during transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: We performed a systematic MEDLINE search of clinical trials of any kind of anesthesia, analgesia or sedation during TRUS guided prostate biopsy published since 2000. We critically analyzed the impact of pain and discomfort associated with the procedure, the described methods for evaluating it and the different techniques that have been described. RESULTS: There is strong evidence in the current literature that patient tolerance and comfort during TRUS guided prostate biopsy can be improved by anesthesia/analgesia. What remains is the need to urge all urologists to introduce it in clinical practice as a routine part of the procedure, whatever the biopsy scheme. CONCLUSIONS: Of the various options periprostatic anesthetic infiltration has been shown to be safe, easy to perform and highly effective. It should be considered the gold standard at the moment, even if the optimal technique remains to be established. Further studies addressing this issue are warranted.

Anesthetics↗
PubMed2005

Gynecomastia and breast pain induced by adjuvant therapy with bicalutamide after radical prostatectomy in patients with prostate cancer: the role of tamoxifen and radiotherapy.

PURPOSE: We investigated the role of tamoxifen and radiotherapy (RT) for the prevention and treatment of gynecomastia and breast pain during adjuvant bicalutamide monotherapy after radical prostatectomy (RP) in patients with prostate cancer. Also, we evaluated their effects on patient hormonal status, quality of life (QOL), sexual function and prostate specific antigen relapse-free survival. MATERIALS AND METHODS: This was a multicenter prospective trial. From January 2002 to February 2004, 102 patients who had undergone RP for localized or locally advanced prostate cancer were recruited and randomized into 3 groups, namely group 1-those receiving only 150 mg bicalutamide as adjuvant hormonal therapy, group 2-those receiving bicalutamide and 10 mg tamoxifen, and group 3-those receiving bicalutamide and RT. Patients in group 1 in whom gynecomastia or breast pain developed were subsequently randomized to receive tamoxifen or RT soon after symptoms started. Gynecomastia, breast pain, prostate specific antigen, QOL, sexual function and hormonal levels were assessed. Minimum followup was 12 months. RESULTS: Of group 1 patients 67% had gynecomastia compared with 8% in group 2 and 34% in group 3. Breast pain was more frequent in group 1 than in groups 2 and 3 (58% vs 7% and 30%, respectively). Differences were significant between groups 1 and 2 (OR 0.12 p <0.001), and groups 1 and 3 (OR 0.52 p < 0.01). In patients in group 1 who had gynecomastia or breast pain a significant decrease in symptoms was achieved in those receiving tamoxifen (p <0.05). Treatments were well tolerated in the 3 groups. No differences in QOL between groups 2 and 3 were found. At a median followup of 26 months we observed 12 biochemical relapses. CONCLUSIONS: Gynecomastia and breast pain induced by bicalutamide monotherapy after RP can be prevented and treated. Tamoxifen has been shown to be more effective and safe than RT in this setting. QOL and sexual function are not negatively influenced by these 2 treatment options.

Aged↗
PubMed2005

Orbital metastasis as a first indication of prostate cancer: a case report.

Prostatic carcinoma accounts for only 3.6% of orbital metastases encountered in clinical practice. We report the clinical presentation and response to treatment of a patient with metastatic prostatic carcinoma to the sella turcica. A 73-year-old man presented with a three-months history of progressive right proptosis associated with increasing diplopia in down-gaze and slightly decreased visual acuity. Gadolinium-MRI scans of the head revealed a left osteoblastic intrasellar mass, displacing the pituitary gland. Laboratory testing revealed a serum PSA level of 22 ng/ml. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinoma (Gleason score 4+3) in both lobes of the prostate. A bone scan was performed showing that the patient had multiple secondary bony lesions. Total androgen blockade was initiated. Moreover, he was referred for radiotherapy of this metastatic lesion to the sella turcica. The visual complaints regressed dramatically within the first month of the treatment. A follow-up MRI scan at 6 months showed almost complete involution of the orbital metastatic process. However the disease subsequently progressed and the patient died 22 months after diagnosis.

Adenocarcinoma↗
PubMed2004

Weekly docetaxel and vinorelbine (VIN-DOX) as first line treatment in patients with hormone refractory prostate cancer.

BACKGROUND: The current study investigated the clinical benefit, the impact on biochemical and objective response and tolerability of weekly docetaxel with vinorelbine (VIN-DOX) in symptomatic patients with hormone refractory prostate cancer (HRPC). METHODS: Patients were treated with docetaxel 25 mg/m2 and vinorelbine 20 mg/m2, intravenously for 6 consecutive weeks followed by a 2 week rest repeatedly until disease progression. Clinical benefit evaluations, based on Karnofsky performance status (KPS) and pain measure, were assessed weekly during therapy. A clinical benefit response was defined as a sustained (> or =4 weeks) improvements in one of these parameters. Changes in prostate-specific antigen (PSA) levels, tumoral response and toxicity also were evaluated. RESULTS: 19 men (median age 68 years), were treated. Overall, 42% of patients achieved a KPS significant change and positive pain response; 47% achieved a 50% or greater reduction in PSA. The objective response rate was observed in 2 of 9 patients with measurable disease (22%). The most important toxicity was neutropenia (Grade 3 = 32%). CONCLUSIONS: The combination of weekly VIN-DOX appears to be feasible. VIN-DOX was found to be associated with improvement in clinical benefit response and biochemical response and well tolerated as first line treatment in HRPC.

Adenocarcinoma↗
PubMed2004

FOLFOX-4 in pre-treated patients with advanced transitional cell carcinoma of the bladder.

BACKGROUND: Despite recent progress in the treatment of advanced urothelial cancer, there continues to be a need to identify new active agents and their toxicity spectra. We conducted a study using FOLFOX-4 (oxaliplatin, fluorouracil, folinic acid) in pre-treated advanced bladder cancer patients. METHODS: Sixteen eligible patients with advanced disease were treated with oxaliplatin (85 mg/m(3)) on day 1 followed by fluorouracil and folinic acid (De Gramont schedule) on days 1 and 2 every 14 days until disease progression. All patients received nutritional support to increase their caloric intake. Objective responses and toxicity were evaluated. Biochemical responses (reduction of markers) and nutritional parameters (increase in body weight and albumin, and reduction in ferritin and C-reactive protein) were also considered. RESULTS: Three patients obtained an objective response (overall response rate 19%). Hematological toxicity and stomatitis were the most commonly noted side effects, but we observed only low (3-4) grade toxicity. In four patients (25%), we observed a reduction in tumoral markers (carcinoembryonic antigen and tissutal polypeptide antigen) and modified nutritional parameters. CONCLUSIONS: Using these doses and schedules of FOLFOX-4 appears to be a promising therapy in patients pre-treated with platinum compounds. More studies are required to assess the possible role of this regimen in the treatment of advanced bladder cancer.

Aged↗
PubMed2003

Statistical design in phase II clinical trials and its application in breast cancer.

Several statistical designs for phase II studies have been proposed, but they are frequently misunderstood or not applied at all. In this review we describe the major characteristics of the available designs. To investigate the extent to which statistical designs were used in some recent phase II studies, and which designs were the most common, we did a survey of 145 trials involving treatment of breast cancer. Studies selected for the survey were published between 1995 and 1999 in one of seven specific oncology journals (all with impact factor consistently higher than 2). 94 of the studies (64.8%) did not have an identifiable statistical design. However, among the 51 studies with statistical design there was a notable heterogeneity in the type of design applied. We put together a list of factors associated with use of statistical design at univariate analysis. These factors included: referral to a previous phase I study, recent trial start date, private sponsorship, single-agent treatment, and multicentre organisation. Single-agent treatment (OR 2.35; 95% CI 1.01-5.51) and multicentre organisation (OR 3.24; 95% CI 1.47-7.15) were independently predictive of the presence of statistical design. Publication in journals with high impact factors and short intervals between the start of the study and publication were also correlated with statistical design.

Analysis of Variance↗
PubMed2003

Adrenalectomy: defining its role in the surgical treatment of renal cell carcinoma.

OBJECTIVES: With the recent widespread use of modern imaging techniques, the frequency of small low-stage renal cell carcinomas (RCC) has grown considerably, giving rise to more conservative surgical approaches. We evaluated the characteristics of adrenal involvement and the accuracy of computerized tomography (CT) in the diagnosis of RCC, defining the real need for adrenalectomy during surgical treatment. METHODS: The medical records of 201 patients undergoing radical nephrectomy and ipsilateral adrenalectomy for localized or advanced RCC, from 1996 to 2002, were analyzed, retrospectively. We considered 76 with stage T1-2 disease and 125 with T3-4N0-1M0-1 disease. In all cases a blinded review of the preoperative abdominal CT was performed. Histopathology records of the surgical specimens were examined to determine the accuracy of the CT in identifying adrenal involvement by RCC. RESULTS: The overall incidence of adrenal metastasis was 4.4%. The mean renal tumor size in patients with adrenal involvement was 7.8 cm. The tumor stage correlated with a probability of adrenal spread (p < 0.05), with T1-2 tumors accounting for 1.3% of cases only. The adrenal gland was diagnosed as abnormal on preoperative CT in 21 patients (10.4%). CT scan demonstrated 88.8% sensitivity, 92.1% specificity, 99.4% negative predictive value and 34.7% positive predictive value for adrenal involvement by RCC. CONCLUSIONS: Adrenal involvement is not likely in patients with localized early stage RCC and adrenalectomy can be omitted in such cases, particularly when CT is negative. However, in selected patients with large high-risk tumors, radical nephrectomy, including removal of the ipsilateral adrenal gland, should be performed.

Adrenalectomy↗
PubMed2003

Involvement of growth factor receptors of the epidermal growth factor receptor family in prostate cancer development and progression to androgen independence.

The development of prostate cancer and the progression from a normal prostate epithelium to androgen-dependent cancer and eventually to hormone-refractory prostate cancer is a multistep process involving several changes in the function of different growth-regulatory signals. In the past 10 years, conflicting results on epidermal growth factor receptor (EGFR) family expression in prostate cancer have been reported. These differences may result from technical differences, lack of standardization of immunohistochemical assays, or different scoring methodologies. Recently, 4 studies have shown experimental evidence of a role of the EGFR family, particularly ErbB-2, in the development of prostate cancer and, more specifically, in the progression to hormone-refractory clinical behavior. These 4 studies were similar in some relevant aspects, such as the patient population. In fact, the patients in each study were divided into 3 groups that represent the progression of prostate cancer. In 3 of 4 studies, a statistically significant increase in ErbB-2 expression was detected by immunohistochemistry in the progression from hormone-dependent to hormone-independent disease. The expression of EGFR was also evaluated in 1 of the 4 studies. In a recent report from our group, a significant increase in EGFR expression was observed in patients treated with radical surgery, in patients who received hormonal therapy as primary therapy before radical prostatectomy, and, finally, in patients with metastatic and hormone-refractory disease. It has been proposed that EGFR family receptors and androgen receptors function synergistically in the absence of androgen suggesting cross-talk between the ErbB-2 and androgen receptor pathways, and that mitogen-activated protein kinase and phosphatidylinositol 3-kinase can be considered the transduction pathways. Finally, clinical trials are currently in progress in patients with prostate cancer testing novel agents that selectively interfere with these receptors, such as trastuzumab, an anti- ErbB-2 monoclonal antibody, and gefitinib (ZD1839, Iressa), a small-molecule selective EGFR tyrosine kinase inhibitor.

Aged↗