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

Przerzuty do kości: możliwości radioterapii

Bone metastases are the consequence of cancerous disease progress frequently. In metastatic stage they can be present in 14-80% of patients depending on localisation and morphological type. In autopsy study this rate can be even higher up to 70-85%. Patients with bone metastases need a multidisciplinar approach. The consultation by a specialistic group should effect in decision to use analgesics, radiotherapy, surgery, chemotherapy , hormonotherapy and biphosphonates. Radiotherapy is one of the main treatment options of high analgesic effectiveness and quite little burden for patient. It can be applied in every radiotherapy centre within a few hours from the admission to the centre. Onkol. Prak. Klin. 2011; 7, 5: 264–268Przerzuty do kości są częstym następstwem rozwoju choroby nowotworowej. W stadium przerzutowym w zależności od lokalizacji i typu morfologicznego mogą wystąpić u 14–80% chorych. W badaniach autopsyjnych ten odsetek jest jeszcze wyższy i może zawierać się w przedziale 70–85%. Leczenie pacjentów z przerzutami do kości powinno obejmować postępowanie wielodyscyplinarne. Wynikiem konsultacji przeprowadzonej przez zespół specjalistów powinna być decyzja obejmująca zastosowanie w różnej kombinacji leków przeciwbólowych, radioterapii, operacji, chemioterapii, leczenia hormonalnego, bisfosfonianów. Radioterapia jest jedną z istotnych opcji leczenia, charakteryzującą się wysoką efektywnością przeciwbólową przy względnie małej uciążliwości dla pacjenta. Może być praktycznie przeprowadzona w każdym zakładzie radioterapii w przeciągu kilku godzin od chwili zgłoszenia się takiego pacjenta do ośrodka. Onkol. Prak. Klin. 2011; 7, 5: 264–26

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

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

Efficacy of samarium 153 and strontium 89 treatment for bone metastases in prostate cancer patients: monotherapy vs. treatment combined with external beam radiotherapy. Preliminary report

BackgroundApproximately 60–80% of metastatic prostate cancer patients suffer from pain caused by bone metastases. Bone metastases have a negative impact on patient performance status.AimThe aim of study was to compare the efficacy of treatment with strontium 89 or samarium 153 in monotherapy vs. radioisotope treatment combined with external beam radiotherapy (EBRT) in prostate cancer patients with bone metastases.Materials/MethodsWe retrospectively analyzed one hundred (n=100) metastatic prostate cancer patients aged between 53 and 84 years, who we divided into four treatment groups: 30 pts received Sr-89 monotherapy; 30 patients received Sm-153 monotherapy; 20 pts received Sr-89 combined with EBRT; and 20 pts received Sm-153 combined with EBRT. Follow-up was 4 months. All patients prior to therapy had their bone metastases confirmed by bone scan examination. Pathologic fractures were excluded and the nature of metastases (osteoblastic/mixed) was evaluated with X-ray films and/or CT and/or MRI. Sr-89 therapy consisted of a standard dose of 150MBq, while Sm-153 was administered proportionally to body weight (37MBq/kg). In combined treatment groups EBRT was given to the dominant metastatic site with 8Gy in one fraction or 20Gy in five daily fractions. Treatment efficacy was determined by change in pain intensity evaluated according to visual analogue scale (VAS), changes in Karnofsky performance status (KPS) and in the use of analgesics.ResultsComplete pain relief (VAS5) was noted in 20% of patients in both monotherapy groups and in 10% and 15% of patients in Sm-153 and Sr-89 combined with EBRT, respectively. Decrease in pain intensity and in the use of analgesics as well as improvement in performance status were statistically significant for combined therapy vs. monotherapy (

Radiation-induced lung injury — what do we know in the era of modern radiotherapy?

Radiation-induced lung injury (RILI) that is usually divided into an early radiation-induced pneumonitis (RIP) and late chronic radiation-induced lung fibrosis (RILF) remains a clinically significant toxicity in radiation oncology. Thus, a thorough understanding of underlying molecular mechanisms and risk factors is crucial. This review, focused on patients treated with modern radiotherapy (RT) techniques, describes the different clinical presentations of RIP, with most typical imaging findings and usefulness of pulmonary function tests and laboratory assessment in differential diagnosis. The most critical patient- and treatment-related predictors are summarized and discussed — age and sex, comorbidities, tumour characteristics, concomitant treatment, and RT-plan parameters. The conventional grading scales and contemporary approach to quantitative assessment (radiomics, CT density changes) is described as well as treatment methods

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

The impact of the time factor on the outcome of a combined treatment of patients with laryngeal cancer

PurposeTo investigate the impact of the time factor on the locoregional control in combined treatment (surgery and postoperative radiotherapy) in patients with advanced laryngeal cancer.Materials and MethodsBetween January 1993 and December 1996, 254 patients with pT3 or pT4 and pN0-pN2 laryngeal cancer were treated by surgery and postoperative radiotherapy (RT). The median age of patients was 56.3 years (range: 30–70 years). The analyzed group consisted of 236 males (92%) and 18 females (8%). In all cases total laryngectomy was performed. 196 out of 254 patients underwent homolateral neck dissection and 58 out of 254 bilateral neck dissection. RT began 45 days postoperatively (range: 22 to 78 days) and continued for 47 days (range: 40–74 days). The primary tumour bed was irradiated to the median total dose of 61.2 Gy (range: 57 – 64 Gy) and all regional lymph nodes were treated in all patients to a dose of 50 Gy. Postoperative RT was indicated in case of close postoperative margins at the tumour site or pathological status of lymph nodes described as pN1 or pN2. Univariate and multivariate analyses were used to determine the predictors for locoregional failure. The following factors were studied for their prognostic importance of locoregional outcome: the overall treatment time (OTT), radiotherapy treatment time (RTT), the interval between surgery and the beginning of radiotherapy, age, sex, pT and pN categories.Results: The actuarial 5-year overall survival rate was 49%, the actuarial loco regional control rate was 70%. The univariate analysis, using a log-rank test indicated that prolongation of the overall treatment time (OTT), the time of radiotherapy (RTT), the interval time between surgery and radiotherapy, and the pN status were predicted for the loco regional control of postoperative radiotherapy. The multivariate analysis using Cox proportional hazard model indicated that only RTT, OTT, and the pathological status of lymph nodes were independent prognostic factors for the loco regional control.Conclusions: The analysis showed that the prolongation of the overall treatment time of the combined modality (OTT) and the time of radiotherapy course (RTT) were independent prognostic time factors correlated with lower loco regional control

The effectiveness of strontium 89 in the treatment of pain caused by bone metastases in patients with prostate cancer

Background. The aim of this study was to evaluate the effectiveness of strontium 89 (Metastron) therapy in the group of prostate cancer patients with multiple bone metastases. Material and methods. The study included 70 patients (aged 53&#8211;84) with prostate cancer and multiple bone metastases detected by scintigraphy and by radiogram - type of metastases (osteoblastic - 55 patients, osteolytic-osteoblastic - 15 patients). Before strontium therapy 34 out of 70 patients received radiotherapy to the spine to prevent spinal cord compression. For assessment of therapy effectiveness; pain relief (VAS scale), a reduction in analgesic use and motor activity (ECOG and Karnofsky scale) were evaluated. Results. We have observed statistically significant pain relief and that the analgesic use decreased to 50% of dose on average. The motor activity of the points evaluated according to ECOG scale and Karnofsky scale was much better (p < 0.05). Conclusions. We conclude that palliative therapy using strontium 89 is effective (88% "good" and "moderate" response rate) and safe for bone pain palliation in patients with multiple prostate cancer bone metastases; it may also improve quality of life.Wstęp. Celem badań była ocena skuteczności leczenia przeciwbólowego przerzutów nowotworowych do kości za pomocą izotopu 89Sr. Materiał i metody. Badaniem objęto 70 pacjentów w zaawansowanym stadium raka stercza z przerzutami do kości. Średnia wieku badanych wynosiła 67 lat. U wszystkich chorych za pomocą metody scyntygraficznej potwierdzono obecność licznych przerzutów nowotworowych do kości; w 55 przypadkach wykazywały one radiologicznie typowe cechy przerzutów osteoblastycznych, w 15 przypadkach miały charakter mieszany. U 34 osób leczenie izotopem strontu skojarzono z radioterapią zmian w kręgosłupie, zagrażających kompresją rdzenia. Efekt leczenia oceniano na podstawie zmiany stanu pacjentów w skali VAS, ECOG, Karnofsky&#8217;ego oraz wielkością przyjmowanych dawek leków przeciwbólowych. Wyniki. Stwierdzono znamienny statystycznie spadek natężenia bólu i o 50% mniejsze zużycie leków przeciwbólowych, a także poprawę stanu w skali ECOG i Karnofsky&#8217;ego (p < 0,05). Wnioski. Paliatywna terapia przerzutów raka stercza do kości prowadzona z zastosowaniem strontu 89 jest skuteczna w 88% przypadków - zmniejsza dolegliwości bólowe oraz istotnie podnosi jakość życia pacjentów

Should we affraid of induced cancer in group of patients after radical radiotherapy of prostate cancer?

Radiotherapy is one of the basic methods of radical treatment of prostate cancer. Because of that getting to know all factors of post-radiation complications, and in consequence the possibility to limit them, is one of the challenges of contemporary radiotherapy.One of the potential complications associated with radiation treatment is radiation-induced cancer. Despite a whole range of epidemiological analyses there is still lacking a fully credible model that would allow one to estimate the magnitude of risk of inducing such cancers. The last decades have seen the entry into clinical practice of technologically advanced methods of radiation therapy, such as the 3DCRT and IMRT. As the previous epidemiological analyses refer mainly to older radiation techniques, there is still a lack of credible data estimating the risk of inducing secondary cancers for new techniques, and in particular IMRT. It should be emphasized that IMRT allows one to escalate the dose, which may contribute to the improvement of radiotherapy effectiveness. From this there follows a new problem to be solved in future, i.e. how the escalation of the dose may influence the magnitude of risk of radiation carcinogenesis.The problem of carcinogenesis may concern the group of younger patients for whom long survival is very likely, and the competitive edge of RT relative to surgery, in particular in the aspect of late complications, has to be thoroughly justified