Apport du 68Ga-PSMA-TEP dans la prise en charge initiale par radiothérapie des cancers de la prostate

Radiotherapy is one of major modality for prostate cancer treatment. Technical improvements allow to deliver higher doses to the tumor, and improve protection of healthy tissues. Those improvements are enlarging indications and change treatment modalities for prostate cancer patients, on primary staging or at time of relapse (local or metastatic). Accounting to recent publications, 68Ga-PSMA PET should have an impact on radiotherapy treatment planning for those patients, especially in case of intermediate to high risk tumor. In case of metastatic disease, early detection of metastasis allows selection of patients with oligo-metastatic cancer for whom local treatments are in development. For localized prostate cancer, diagnosis of nodal extension permit volumes and doses modifications for radiotherapy. An accurate detection of the dominant intra-prostatic lesion gives the possibility of a focalized dose escalation to this significant cancer (“index lesions”). This new treatment strategies coming from technical progress are currently evaluated to assess their clinical benefit.     

Cancer de prostate métastatique résistant à la castration : le point de vue de l’oncologue médical

Most of patient suffering from a prostate cancer will develop a castration resistance. In this common and clinically challenging situation, chemotherapy was not considered very useful until mid 2000s. Docetaxel is now recognized as a standard of care, improving overall survival and quality of life. However, new drugs are needed. Two compounds (cabazitaxel and abiraterone) are now underway to official registration and an autologous vaccin strategy (Sipuleucel) demonstrated a benefit in survival. Based on a greater knowledge of biology, many other agents are currently under development, such as new specific peripheral anti-androgens, anti-angiogenic therapies, or proteasome inhibitors. All these new drugs are promising and may provide more efficient therapies against this incurable disease in the near future.     

Pathologies de la prostate : actualités en médecine nucléaire (diagnostic et thérapeutique)

Nuclear medicine could significantly contribute to management of patients with prostate carcinoma. Apart from bone scintigraphy, and success of sentinel lymph node procedure, from a diagnosis point of view ¹⁸F-fluorocholine, which is now disposable, will certainly allow better staging accuracy, better efficiency of recurrences detection, and better treatments evaluation. Regarding to treatments, several radiopharmaceuticals demonstrated their efficiency as palliative treatment of painful bone metastasis, and maybe in the near future will contribute to curative treatment when associated to chemotherapy.     

Intérêt des traceurs de l’hypoxie en radiothérapie

Tumor hypoxia is a major parameter of radioresistance. Hypoxia PET imaging using several radiotracers (F-Miso, FAZA, Cu-ATSM, EF5…) may help predict response to radiotherapy. Hypoxic area evaluation may also help select patients for hypoxia-targeting drugs, and thus reinforcing radiotherapy effects. Hypoxia imaging may also be fused with radiotherapy planning CT to define radioresistance areas that may be boosted by dose-painting radiotherapy. Despite several difficulties (patient positioning, organ and tumor motion, image definition…), targeting hypoxic regions within tumors is one of the most promising research strategies of modern radiotherapy.     

Radiothérapie vectorisée : les nouvelles molécules

Although the efficacy of radionuclide therapy has been demonstrated in several indications, the development of this new therapeutic modality is limited. However, promising results have been obtained, especially using different radiolabeled somatotatin analogs for neuroendocrine tumors or radioimmunotherapy for lymphoma. Toxicity is limited, particularly if patients are selected based on their background. The use of new vectors (bombesin, anti-PMSA monoclonal antibody), pretargeting system and innovative radionuclides (Copper-67, Astatine-211) suggests interesting perspectives, particularly to target small tumor masses or residual disease.     

Irathérapie génique anticancéreuse utilisant le NIS : une approche très prometteuse

The symporter Na/iodine (NIS) is a recently discovered membrane protein, recognized to be at the origin of accumulation of iodine in the thyroid, salivary glands, stomach and mammary glands during lactation. If its intrinsic property served as the basis for nuclear imaging and radiotherapy metabolic of differentiated thyroid cancers and their metastases, the cloning of its gene provides a powerful strategy for cytoreductive gene therapy, based on the targeted transfer of this last one in all types of cancer cells. Its expression gives the ability to these cells to accumulate iodine. The aim is to benefit from the advantages of radioiodine therapy (efficiency, reduced side effects) and to optimize the management of thyroid cancer. This approach offers an attractive therapeutic alternative for non-thyroidal cancers, especially in the context of a multimodal approach. Techniques and equipments necessary for the first clinical trials are already existing in the departments of nuclear medicine. The perspectives of clinical application, however, require a better knowledge of the regulation of expression and functionality of NIS. After a review of the biology of NIS, our work aims to recount the results of different tests that have demonstrated the benefits of this approach, its limitations and prospects for its improvement.     

Le cancer de la prostate: Acquis et challenges pour l'an 2000

Principles of the diagnosis and treatment of prostate cancer at any stage are still improving. Early diagnosis is accessible throughout the use of the PSA test associated with digital rectal examination which lead to indicate transrectal biopsies. This allowed to treat patients at an earlier stage and significantly improved prognosis in the case of organ confined disease. Progress made in the radical prostatectomy technique have contributed to decrease the postoperative morbidity and is the treatment of reference in clinically localized disease. Radiation therapy still remains a valuable alternative, however, results are more difficult to evaluate. Hormonal treatment using androgen deprivation is indicated at the stage of metastasis. LHRH agonist associated with anti antiandrogens are as much efficacious as surgical castration. Unfortunately, the prognosis of advanced disease remains unpredictable. Objectives for the future will be to improve the diagnostic and staging of prostate cancer et to better define therapeutic indications; better understand the effects of androgen deprivation; and to propose new therapies for hormone refractory cancers.     

Cancer de la prostate : utilité de la TEP-TDM à la F-fluorocholine

In oncology, positron emission computed tomography (PET/CT) has become an essential tool for initial staging, response evaluation and follow-up of cancer patients. Most of the frequent tumors (lung, breast, esophagus, and lymphomas) are highly avid for ¹⁸F-fluorodeoxyglucose (¹⁸FDG), but prostate cancer has not demonstrated significant uptake of FDG. The development of new tracers labeled with ¹⁸F such as choline analogs allowed already to obtain interesting results particularly in patients with biological relapse and inconclusive conventional imaging work-up. The impact of ¹⁸F-flurocholine PET/CT on patient management needs to be validated in large studies, but many centers use already this examination in order to guide further management, including radiotherapy planning.     

Improving outcomes in high-risk prostate cancer with radiotherapy

There have been significant improvements in the radiotherapeutic management of patients with high risk prostate cancer. Randomized trials have clearly demonstrated improved outcomes with the combination of radiotherapy in conjunction with androgen deprivation. While these trials have utilized low doses of radiotherapy in the range of 70 Gy, recent studies have suggested that significant benefits of combined androgen deprivation therapy with dose escalated radiotherapy are also observed. The use of high radiation dose levels in the setting of high risk prostate cancer is important, and strategies which combine external beam radiotherapy with a brachytherapy boost may provide an opportunity for even greater intensification of the radiation dose to the prostate target. Systemic therapies, second generation anti-androgen therapy and novel targeted agents integrated with radiotherapy will open up new vistas and challenges for further improved outcomes in patients with high-risk disease.     

Perturbateurs endocriniens environnementaux et cancers hormonodépendants. De nouveaux facteurs de risque ?

The involvement of environmental endocrine disruptors (EED) in hormone dependent carcinogenesis is supported by: (1) in utero exposure to distilbene, a human experimental model which led to vaginal adenocarcinoma in the young daughter and an increased risk of breast cancer after 40 years; (2) epidemiological case/control studies showing although many confounders and methodological biais, a correlation between blood, adipose tissue or tumoral EED levels and hormone dependent cancers (breast cancer and PCB, PAH and dioxine levels; prostate cancer and chlordecone levels; testicular germ cell cancer and of PCB, HCB or chlordane blood levels of the mothers); (3) experimental models able to induce in rodents after fetal or perinatal exposure to diéthylstilbestrol (DES), bisphenol A or atrazine, adult breast or prostate cancers; (4) in vitro malignant cell studies showing how EEDs like bisphenol A are able to interfere with prostate, breast or testicular germ cell proliferation, apoptosis and survey. All these reports suggest a reassessment of EED chemotoxicity during carcinogenesis which needs to include low doses of EEDs with additive or synergistic mixture during critical windows of exposure such as fetal or perinatal periods leading to stable epigenetic modifications which do not change the genetic code but may participate to the malignant transformation and/or promotion.     

Prostate cancer radiation therapy: A physician’s perspective

Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician’s perspective.     

Étude de faisabilité du ganglion sentinelle dans le cancer de la prostate par cœlioscopie : premiers résultats

Objectives

The standard lymphadenectomy is currently a challenge in the management of prostate cancer. The aim of this prospective study was to evaluate the performance of the sentinel lymph node (SLN) by laparoscopy in patients with localized prostate cancer, candidates for local treatment.

Patients and methods

Patients were injected transrectal ultrasound-guided with 0.3 mL/100MBq 99^mTc-Sulfur rhenium colloid in each prostatic lobe, the day before surgery. Lymphoscintigraphy was performed after 2 hours. The detection was realized intraoperatively with a laparoscopic probe (Gamma Sup Clerad^®) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by HPS staining and followed by immunochemistry if SLN was free.

Results

Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases (D’Amico), PSA median 9.5 ng/mL [6–130], were included in the study. The lymphoscintigraphic detection rate was 94.2% (66/70) and intraoperative of 97.0% (68/70). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14.0%). The internal iliac region is the first metastatic site (40.9%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59.0% of lymph node metastases.

Conclusion

The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limits the risk of surgical extended dissection while maintaining the accuracy of the information.     

Cancer de la prostate : les marqueurs biologiques

Normal prostate cells and prostate cancer cells produce prostate-specific antigen (PSA): thus, it is frequently increased in non-malignant conditions such as prostatitis and benign prostatic hyperplasia. Indeed, PSA is an excellent biomarker to monitor disease progression. The low diagnostic specificity of PSA leads to many false-positive and a large number of biopsies. These well-recognized limitations of PSA suggest that new prostate cancer biomarkers could play a useful role in reducing the number of unnecessary biopsies.     

Tomographie par émission de positons et cancer de la prostate

Positron emission tomography (PET) is a major imaging modality in oncology. Fluorodeoxyglucose (FDG) PET is of limited usefulness in prostate cancer, be it for initial staging or for detection of recurrence. New PET tracers could improve PET performances in prostate cancer staging and when recurrence is suspected. Lipid metabolism tracers, such as choline and fluorine-18-labelled choline analogues, seem to be promising in these indications. The impact of these PET examinations on patient management should be further evaluated, taking into consideration the new therapeutic strategies, in particular salvage local treatment in case of isolated local recurrence.     

Radiopotentiation of enzalutamide over human prostate cancer cells as assessed by real-time cell monitoring

AimTo evaluate the radiopotentiation of enzalutamide in human prostate cancer cells.BackgroundWhile radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy.Materials and methodsHere, we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real-time cell analysis (RTCA), androgen-sensitive LNCaP cells (Lymph Node Carcinoma of the Prostate) and androgen-independent PC-3. Both cell lines were highly resistant to high doses of radiotherapy.ResultsA pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade.ConclusionsThese results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.     

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.     

Place de la scintigraphie et de la radiothérapie dans les évacuations sanitaires hors du Bénin de 2006 à 2010

Because of the insufficiency of technical tray in Benin hospitals, medical practitioners have recourse to medical evacuation abroad for better taking care of patients. This study presents statistics of medical evacuations made outside Benin, for scintigraphy and radiotherapy, funded by the government from January 2006 to December 2010. For a total of 769 patients from 2- to 80-years-old, 229 patients (29.8%) were concerned by these two indications. Urology, cardiology, and gynecology were the most important specialties, which provide medical evacuations in 24%, 23.6% and 13.15% of cases respectively. The pathologies involved were essentially malignant tumors in 66.8% of cases and heart diseases in 16.2% of cases. The strengthening of medical instrument and staff through nuclear medicine and radiotherapy center should contribute to improve the performance of Benin sanitary system and to reduce the medical evacuations abroad.     

Apport de l’imagerie hybride TEMP/TDM dans la détection des ganglions sentinelles : à propos de 32 cas

Objectives

Retrospective evaluation of the SPECT/CT role in the Sentinel Lymph Node identification.

Patients and methods

Thirty-two patients underwent a lymphoscintigraphy with SPECT/CT imaging. Those patients presented several cancer types (16 melanoma, one squamous cell carcinoma, three breast cancers, eight vulvar cancers, three cervical cancers).

Results

The scintigraphic detection rate was 81% with planar imaging while this rate was 89% with SPECT/CT. The SPECT/CT provided an additional quantitative information in 66% cases. Moreover, the quality of the interpretation was better in two different conditions (planar interpretation followed by routine and blinded SPECT/CT interpretation) with SPECT/CT. In our study, the false negative rate is 4.5%.

Conclusions

SPECT/CT provides quantitative and qualitative informations in the sentinel lymph node detection. Therefore, it can be a valuable tool for the surgeon to find and harvest the sentinel lymph node especially where the lymphatic drainage pattern can be unusual or hard to predict (cervical or trunk localisation). It's a new tool for preoperative detection and it can decrease the false negative rate.     

Results of combined radiotherapy and hormonal treatment of prostate cancer patients with initial PSA value >40 ng/ml

AimTo evaluate the outcome of prostate cancer patients with initial PSA value >40 ng/ml.BackgroundThe outcome of prostate cancer patients with very high initial PSA value is not known and patients are frequently treated with palliative intent. We analyzed the outcome of radical combined hormonal treatment and radiotherapy in prostate cancer patients with initial PSA value >40 ng/ml.MethodsBetween January 2003 and December 2007 we treated, with curative intent, 56 patients with non-metastatic prostate cancer and initial PSA value >40 ng/ml. The treatment consisted of two months of neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68–78 Gy, conformal technique) and an optional two-year adjuvant hormonal treatment.ResultsThe median time of follow up was 61 months. 5-Year overall survival was 90%. 5-Year biochemical disease free survival was 62%. T stage, Gleason score, PSA value, and radiotherapy dose did not significantly influence the outcome. Late genitourinal and gastrointestinal toxicity was acceptable.ConclusionRadical treatment in combination with hormonal treatment and radiotherapy can be recommended for this subgroup of prostate cancer patients with good performance status and life expectancy.