Image-guided robotic radiosurgery as salvage therapy for locally recurrent prostate cancer after external beam irradiation: retrospective feasibility study on six cases.

AIMS AND BACKGROUND: Technological advances in treatment planning and execution are providing new potential opportunities in the treatment of recurrent prostate cancer. This study was conducted to evaluate the feasibility and safety of reirradiation with image-guided radiosurgery using CyberKnife, a robotic arm-driven compact linear accelerator, for intraprostatic recurrence after external beam radiotherapy (EBRT). METHODS: Between September 2007 and May 2008, 6 patients diagnosed with locally recurrent prostate cancer after EBRT were treated using the CyberKnife system. The total reirradiation dose was 30 Gy in five fractions. Prior to radiosurgery four patients were treated with androgen-deprivation therapy. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and the Houston-Phoenix definition (PSA nadir + 2 ng/mL) were used for toxicity and biochemical failure evaluation, respectively. RESULTS: After a median follow-up of 11.2 months (range, 9.6-18.6 months), all patients are alive with no evidence of severe urinary or rectal acute morbidity. Local control cannot be exactly determined due to the short follow-up and the bias of the use of androgen ablation. Four patients had biochemical failure, three of them with clinical failure evidence (lymph node, bone and lung metastasis, respectively): none of these patients had clinical evidence of tumor persistence in the prostate. CONCLUSIONS: Salvage radiosurgery with CyberKnife after irradiation is feasible with low urinary and rectal morbidity. A longer follow-up and a larger number of patients are necessary to evaluate its effectiveness and optimal patient selection criteria.

Dose distribution in 3-dimensional conformal radiotherapy for prostate cancer: comparison of two treatment techniques (six coplanar fields and two dynamic arcs).

PURPOSE: To compare dose distribution for two techniques of 3-dimensional conformal radiotherapy (RT): 6-field technique (6F) and 2-dynamic arc therapy (2DA). METHODS AND MATERIALS: Thirty nonmetastatic prostate cancer patients were included. In each patient, two treatment plans were prepared: with six coplanar fields (45 degrees , 90 degrees , 135 degrees , 225 degrees , 270 degrees , 315 degrees ) and with two dynamic lateral 100 degrees -wide arcs (40-140 degrees , 220-320 degrees ). Dose-volume histograms (DVHs) were computed and mean area under curve (AUC) values were calculated for the DVHs of Planning Target Volume (PTV), rectum, urinary bladder and femoral heads. Doses given to 30% of rectum (DR(30)), to 60% of rectum (DR(60)), to 50% of bladder (DB(50)), to 50% of femoral head (DF(50)) and to 95% of PTV (DPTV(95)) were reported as a percentage of the total dose. RESULTS: Mean DR(30) and DR(60) for 6F and 2DA were 75.8%, 51.5% and 72.2%, 37.2%, respectively. Mean DB(50) for 6F and 2DA were 68% and 64.2%, respectively. Mean right DF(50) for 6F and 2DA were 35.4% and 45.5%, respectively. Mean DPTV(95) for 6F and 2DA were 99% and 99.2%, respectively. Mean AUCs of DVHs of rectum and urinary bladder were significantly higher for 6F (this was more evident for small PTV and in the intermediate dose range). Mean AUC of DVHs of PTV and femoral heads were significantly higher for 2DA. CONCLUSIONS: Both 6F and 2DA offer good dose distribution for PTV. 2DA allows for significantly better sparing of rectum and urinary bladder with slightly worse femoral head dose distribution. Further study is warranted in order to establish the clinical relevance of these differences.

Long-term follow-up using testicle-sparing surgery for Leydig cell tumor.

BACKGROUND: Our objective was to perform a long-term evaluation of conservative surgical treatment of Leydig cell tumors. PATIENTS AND METHODS: A multicenter retrospective clinical study was performed at 6 European centers. Case files of all patients diagnosed with Leydig cell tumor and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumor marker assays, scrotal and abdominal ultrasonography, chest radiography, and endocrinologic examination. RESULTS: From 1987 to 2006, 22 patients with Leydig cell tumor underwent conservative surgery. Mean patient age was 35 years (range, 5-61 years). Mean follow-up was 180 months (range, 77-290 months). No local recurrence or metastasis was observed. Patients presented with a palpable testicular nodule (3 patients [13.7%]), a nodule diagnosed by ultrasonography (15 patients [68.2%]), gynecomastia (2 patients [9.1%]), precocious pseudopuberty (1 patient [4.5%]), or scrotal pain (1 patient [4.5%]). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 22 patients (91%). Mean histologic size of the nodule was 1.11 cm. Follow-up was conducted for all patients every 3 to 6 months, with physical examination, tumor marker assays, scrotal and abdominal ultrasonography, chest radiography, and computed tomography (CT). No local recurrences or metastases were observed. One hundred percent of patients are still alive with a 100% disease-free survival. CONCLUSIONS: When diagnosed and treated early, long-term favorable outcomes are seen at follow-up in Leydig cell tumors, even with its potential metastatic behavior. In these patients, testicle-sparing surgery proved to be a feasible and safe choice and could be regarded as the first line of therapy.

A randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with prostate cancer. Efficacy monitored by karyometry.

OBJECTIVE: Presurgical, window of opportunity trials have been proposed as a model to assess the activity of preventive and therapeutic interventions in a cost-effective manner in prostate cancer (CaP). The aim of the study was to explore karyometry as a method for monitoring the efficacy of intervention with preventive agents in patients with CaP. MATERIALS AND METHODS: The material used in this investigation was from the 2F study, i.e., an Italian prospective randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with CaP. Image analysis was performed in 16 cases treated with finasteride, 24 with flutamide, and 20 with placebo. For all these cases, CaP and normal looking secretory epithelium were present in the pretreatment biopsies as well as the post-treatment ex-vivo biopsies obtained from the radical prostatectomy specimens. RESULTS: To establish a direction of nuclear change from normal to malignancy, i.e., the so-called line of progression, a discriminant function was derived with the normal looking epithelium in the pretreatment biopsies as one endpoint, and the CaP in the pretreatment biopsies as the other. The discriminant function was then applied to the post-treatment groups. The increase in relative nuclear area was the dominant feature. In the placebo group, 15 out of 20 CaP (75%) cases had a higher discriminant function score at the end of study, with a significant increase of the mean score by 90%. The flutamide treated CaP cases had increased discriminant function scores in 19 out of 24 cases (79%) and an increase of the mean score by 43%; the 5 cases with lower scores involved only minor reductions. In contrast, the finasteride treated CaP cases had increased discriminant function scores for 8 out of 16 cases (50%), but the increase in the mean score was by only 8%. CONCLUSION: This exploratory study establishes that karyometric monitoring can track the results of subtle nuclear changes induced by preventive interventions in men with CaP, thus allowing assessment of agent activity in a cost-effective manner.

Conservative surgical therapy for leydig cell tumor.

PURPOSE: We performed a long-term evaluation of conservative surgical treatment of benign Leydig cell tumor. MATERIALS AND METHODS: A multicenter retrospective clinical study was performed at 6 European centers. Case files of all patients diagnosed with Leydig cell tumor and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumor marker assays, scrotal and abdominal ultrasound, chest x-ray, and an endocrinological examination. RESULTS: From 1987 to 2006, 22 patients with Leydig cell tumor underwent conservative surgery. Mean patient age was 35 years (range 5 to 61). Mean followup was 47 months (range 1 to 230). No local recurrence or metastasis was observed. Patients presented with a palpable testicular nodule (3 patients, 13.7%) or a nodule diagnosed by ultrasound (15 patients, 68.2%), gynecomastia (2 patients, 9.1%), precocious pseudopuberty (1 patient, 4.5%) or scrotal pain (1 patient, 4.5%). Three patients were monorchid after contralateral orchiectomy for inguinal hernia repair (1 patient, 28 years before surgery) and nonseminomatous germ cell tumor (2 patients, 1 month and 6 years before surgery). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 22 cases (91.0%). Mean histological size of the nodule was 1.11 cm (range 0.5 to 2.5). Preoperative FSH and LH levels were high in 4 patients. Tumor markers were normal before and after surgery. Followup was conducted for all patients every 3 to 6 months with physical examination, tumor markers, scrotal and abdominal ultrasound, chest x-ray. Six patients (27.3%) underwent abdominal computerized tomography. CONCLUSIONS: When diagnosed early Leydig cell tumors present a favorable followup. In select cases with motivated patients, conservative surgery proved to be a feasible and safe choice.