Hormonal therapy combined with radiotherapy in locally advanced prostate cancer

At present radiation therapy and radical prostatectomy are considered to be the treatment of choice for clinical T1-T2 prostate cancer. In a more advanced stage of the disease (T3) 10-year overall survival is observed in approximately 40% of patients treated with conventional radiotherapy. So far only a few methods for improving the efficacy of radiotherapy have been introduced. One of them is a three-dimensional conformal radiotherapy with 3 dimensional treatment planning. These novel methods make it possible to escalate the dose to the target and protect healthy tissue at the same time. The optimal volume of irradiation, total dose, fraction dose, techniques of radiotherapy, and the end points used during the follow-up are open to debate. In recent years a few clinical trials involving hormonal therapy and radiotherapy have been carried out. The most important of these are: RTOG 8307, RTOG 8610, RTOG 9202, and EORTC 22863.In the RTOG 8307 trial the comparison of outcomes of a combined treatment with a matched-control group of patients treated by radiotherapy alone has shown that adding hormonal therapy to radiotherapy resulted in a better outcome. Another trials RTOG 8531 and RTOG 8610 produced benefit due to the implementation of hormonal therapy in radiotherapy. The EORTC trial No. 22863 showed improvement in the 5-year overall survival when hormonal therapy after the completion of radiotherapy was continued for 3 years in the investigational arm. The RTOG 9202 study indicated benefit obtained from 2 years of adjuvant hormonal therapy.The results of these trials have had a substantial impact on the management of locally advanced prostate cancer, but there are still questions that have to be answered. There is no doubt that hormonal therapy is an important component of the management of locally advanced prostate cancer. Still the optimal combination of drugs and the timing of such treatment remains controversial. Considering the potential side effects of a combined treatment on the quality of life of patients and care costs, additional properly designed randomised trials are needed to identify the subgroup of patients who will obtain the greatest benefit. Currently, it can be concluded that in the group of patients with a high risk of relapse by adding hormonal therapy to radiotherapy the outcome of treatment in patients with prostate cancer has improved

Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented

Interleukin-6 (IL-6) and C-reactive protein (CRP) concentration prior to total nephrectomy are prognostic factors in localized renal cell carcinoma (RCC)

AbstractBackgroundRadical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient.AimThe aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC.Materials and methodsOur prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0.ResultsStatistically significant relationships were found between the concentration of CRP before the operation and OS (p=0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p=0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p=0.0096) and CSS (p=0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times.ConclusionsResults of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS

Benefit of Whole Pelvic Radiotherapy Combined with Neoadjuvant Androgen Deprivation for the High-Risk Prostate Cancer

Aim. To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. Material and Methods. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. Results. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. Conclusions. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed

Hormonal therapy and 3D conformal radiotherapy in prostate cancer: early toxicity of combined treatment

PurposeTo evaluate acute toxicity of combined treatment (androgen ablation and high-dose 3D conformal radiotherapy [3D-CRT]) in patients with a localized cancer of prostate.Materials and methodsBetween April 1999 and March 2000, at the Greatpoland Cancer Centre in Poznań, 22 patients with prostate cancer (T1–T3 N0 M0) were treated with 3 D conformal radiation therapy and hormonal therapy. Patients represented a localized disease (T1 = 4 patients, T2 = 11 patients), and locally disease (T3 = 7 patients). No patients had clinically detectable distant metastases. Neoadjuvant androgen ablation therapy (bilateral orchiectomy or LH-RH agonists and flutamide) was administered to all patients. Radiotherapy was performed using 15 MV photons in the daily fraction of 1.8 Gy to the total median dose of 70.2 Gy (range, 67.8 to 72 Gy). Acute toxicities were evaluated according to the Radiation Therapy Oncology Group morbidity scoring scale.ResultsAll patients completed the entire course of radiotherapy and were assessable for evaluation of acute toxicities. The most common side effects of androgen ablation were “hot flushes” and gynecomastia, although these were mild. The main problems during irradiation and a few weeks after the completion of radiotherapy were related to:-the genitourinary tract (urgency, nocturia, dysuria) with toxicities of grade 0 and 1 (80% of patients) and grade 2 (20% of patients)-the gastrointestinal tract (rectal discomfort and mild diarrhea) with toxicities grade 0 and 1 (75% of patients) and grade 2 (25% of patients).ConclusionsPreliminary results of combined treatment (androgen ablation and 3 D-CRT) have suggested that such modality is well tolerated with only modest acute toxicities of the gastrointestinal and genitourinary tracts

Conformal radiotherapy (3D CRT) for non-metastatic androgen-independent prostate cancer: costly and sophisticated but ineffective treatment?

PurposePatients with diagnosis of hormone-refractory prostate cancers (HRPC) present a very heterogeneous population, and therefore it has been proposed to sub-categorize them into two subgroups depending on presence or absence of distant metastases. While the former subgroup has been typically treated with palliative intention, for the latter apparently there is no standard approach. The role of three-dimensional conformal radiotherapy (3D-CRT) for this subgroup has not been well documented in the literature. Thus, the purpose of this work is to analyze the results of treatment of non-metastatic androgen-refractory prostate cancer (ARPC) with 3D-CRT and to investigate the potential prognostic factors which influenced the results.Material and MethodsOf 424 patients with diagnosis of localized and locally advanced prostate cancer who were treated between 1999 and 2004 in our centre, forty-three (n=43) patients were classified as non-metastatic ARPC. Distant metastases were excluded by negative bone scan, negative chest X-ray and negative pelvic CT for lymph node metastases. The median pre-hormone therapy PSA (pre-HT PSA) level for this group was 24 ng/ml (range 1 to 120) and 5.7 ng/ml (range 0.06 to 27) at the beginning of radiotherapy (pre-RT PSA). Clinical T stage distribution, defined according to the 2002 AJCC, was as follows: T1c = 12, T2 = 23, and T3 = 8 patients, respectively. Of 44 patients, 39 had a Gleason score of 2-7 and 4 had a Gleason score of 8–10. All patients with diagnosis of non-metastatic ARPC were treated with 3D-CRT with the daily fraction dose of 2 Gy to a median total dose of 68 Gy (range from 60 to 74 Gy). The median duration of androgen ablation therapy before RT was 26 months (range from 7 to 96). The median time of follow-up after 3D-CRT was 27 months (range from 13 to 62) and from the beginning of androgen ablation was 53 months (range from 20 to 158). The following prognostic factors were evaluated in univariate and multivariate analysis: age, pre-HT PSA, pre-RT PSA, Gleason score, total dose, PSA doubling time (PSADT 6 months).ResultsThe 5-year actuarial overall survival was 82% and 5-year clinical relapse free-survival rate was 49%. During the follow-up 14 patients developed disease progression (locoregional and/or distant and/or biochemical) and two patients died of prostate cancer. The univariate analysis indicated that pre-HT PSA > 20 ng/ml, pre-RT PSA > 4ng/ml, and the high-risk group defined according to NCCN criteria (PSA >20 ng/ml and Gleason score >7) were statistically significant factors for the risk of disease progression.ConclusionsThree-dimensional conformal radiotherapy for patients with non-metastatic ARPC is a valuable method of treatment for the subgroup of patients with pre-HT PS

Penile cancer – case report and literature review

Penile cancer occurs quite seldom, mostly in men around 60 years of age. However, penile squamous cell carcinoma is also observed in younger men. Etiology remains unclear but we can recognize some risk factors such as poor hygiene for example. The authors report a case of a patient who refused treatment in early stages of the disease and was treated only after disease progression. Applied surgical treatment, unfortunately, proved to be insufficient and the patient was transferred to complete therapy at the oncology department. This case inspired us to recall the basic diagnostic and therapeutic methods used at the time of diagnosis of the penile tumor

Interleukin-6 (IL-6) and C-reactive protein (CRP) concentration prior to total nephrectomy are prognostic factors in localized renal cell carcinoma (RCC)

BackgroundRadical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient.AimThe aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC.Materials and methodsOur prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0.ResultsStatistically significant relationships were found between the concentration of CRP before the operation and OS (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.0096) and CSS (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times.ConclusionsResults of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS

2009. Benefit of whole pelvic radiotherapy combined with neoadjuvant androgen deprivation for the high-risk prostate

Aim. To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. Material and Methods. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. Results. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. Conclusions. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed