An evidence-based estimation of local control and survival benefit of radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Survival benefits from radiotherapy for breast cancer described in randomised trials represent only those patients eligible for trials. We estimated the benefit of radiotherapy as an adjuvant treatment for the entire population of breast cancer patients if evidence-based treatment guidelines were followed. MATERIALS AND METHODS: Evidences on 10-year local control and overall survival gain (radiotherapy vs no radiotherapy) were identified from review of literature. The data were incorporated into the optimal radiotherapy utilization tree that we previously reported for all categories of breast cancer patients and overall local control and survival benefits were estimated. RESULTS: The gains in 10-year local control and overall survival from optimal treatment of all breast cancer patients were 11.1% (95% CI 10.8-11.2%) and 3.1% (95% CI 3.0-3.4%), respectively. The stage-based estimates in local control and survival benefit were: 8% and 0% for Ductal Carcinoma in situ (DCIS), 12% and 2% for stage I-II cancers and 13% and 20% for stage III cancers. CONCLUSIONS: Our model was able to estimate the contribution of radiotherapy in breast cancer treatment if all patients were treated according to the recommended guidelines. These estimates could be used to benchmark population-based survival reports and to assess the cost-effectiveness of radiotherapy for breast cancer treatment.     

Metastatic Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia Over Three Decades

Background: Registry data from four major public hospitals indicate trends over three decades from 1980to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stageIV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards modelsfor investigating disease-specific survival and multiple logistic regression analyses for indicating first-roundtreatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses.Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancerdeath approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumourdifferentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggestingreasonable equity in service provision. About 74% of cases were treated surgically and this proportion increasedover time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61%for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of thecases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemictherapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportionshaving: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46%respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offeredtherapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and amongrectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases insurvivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies andsurgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns ofchange accord with clinical guideline recommendations.     

Floor of mouth carcinoma: surgery still the dominant mode of treatment

Introduction: To evaluate the care and outcomes for patients presenting with floor of mouth (FOM) cancers. Methods: In this Ethics‐approved audit, all eligible patients were evaluated with eligibility defined as having a squamous cell carcinoma originating in the FOM. Patient, disease and treatment factors were defined. Primary end points were ultimate local/regional control and cancer‐specific survival. These were analysed according to the Kaplan‐Meier method. The log‐rank test was used to determine statistical significance between survival curves. Multivariate analysis was conducted using Cox regression. Results: A total of 157 patients were eligible for analysis, 76% males and 24% females, with 38 (24%) having a prior diagnosis of cancer. Surgery was performed in 126 patients (54 with pre/postoperative radiotherapy), radiotherapy only in 30 patients and chemotherapy only in 1 patient. Surgery had the best local control (85%), with 23/30 (77%) patients having radiotherapy failing locally. Ultimate regional control was achieved in 89% of patients, while new primaries occurred in 45 (29%) Conclusions: Surgery remains an essential component of the treatment of patients with FOM cancers, with a high likelihood of other cancers developing.     

Progress in the management of limited‐stage small cell lung cancer

Approximately 15% of lung cancer cases are of the small cell subtype, but this variant is highly aggressive and is often diagnosed at advanced stages. Outcomes after current treatment regimens have been poor, with 5‐year survival rates as low as 25% for patients with limited‐stage disease. Advances in therapy for small cell lung cancer have included the development of more effective chemotherapeutic agents and radiation techniques. For example, hyperfractionated radiotherapy given early in the course of the disease can reduce local recurrence and extend survival. Other technologic advances in radiation planning and delivery such as intensity‐modulated radiotherapy, image‐guided adaptive radiotherapy, and 4‐dimensional computed tomography/positron emission tomography have facilitated the design of treatment volumes that closely conform to the shape of the tumor, which allows higher radiation doses to be given while minimizing radiation‐induced toxicity to adjacent structures. Future improvements in outcomes will require clarifying the molecular basis for this disease. Cancer 2014;120:790–798 . © 2013 American Cancer Society.     

Local Surgical,Ablative, and Radiation Treatment of Metastases

Because local therapies directed toward a specific tumor mass are known to be effective for treating early‐stage cancers, it should be no surprise that there has been considerable historical experience using local therapies for metastatic disease. In more recent years, increasing interest in the use of local therapy for metastases likely has arisen from improvements in systemic therapy. In the absence of effective systemic therapies, such local treatments were often considered futile given both the difficulty in eliminating all sites of identifiable metastatic disease as well as realities regarding the rapid natural history of uncontrolled tumor dissemination. However, with a higher likelihood of patients surviving longer after effective systemic therapy, even if not cured, the goal of the eradication of residual metastases via potent local therapies can be rationalized. However, this rationalization should be evidence‐based so as to avoid harming patients for no established benefit. Although surgical metastectomy remains the most common and first‐line standard among local therapies, nonsurgical alternatives, including thermal ablation and stereotactic body radiotherapy, have become increasingly popular because they are generally less invasive than surgery and have demonstrated considerable promise in eradicating macroscopic tumor. Rather than eliminating the need for local therapies, improvements in systemic therapies appear to be increasing the prudent utilization of modern local therapies in patients presenting with more advanced cancer. CA Cancer J Clin 2009;59:145–170. © 2009 American Cancer Society, Inc.     

Estimation of an Optimal Utilisation Rate for Palliative Radiotherapy in Newly Diagnosed Cancer Patients

AimsAn optimal utilisation rate for palliative radiotherapy in newly diagnosed cancers will be useful in the planning and delivery of cancer services and has not been reported to date. The aim of this study was to estimate the proportion of new cases of cancer that should receive palliative radiotherapy as their first course of radiotherapy at some time during the course of their illness.Materials and methodsA previously developed model depicting indications for radiotherapy was merged with Australian cancer epidemiological data and re-analysed to identify palliative or radical treatment end points. Palliative radiotherapy end points were further divided by treatment site. The optimal palliative radiotherapy utilisation rates were compared with actual radiotherapy utilisation data for newly diagnosed cancers.ResultsFourteen per cent of all new cancer cases should optimally receive palliative radiotherapy as their first course of radiotherapy treatment. Comparisons with actual radiotherapy utilisation rates from New South Wales, Australia, show that for some common cancers, more newly diagnosed patients receive palliative radiotherapy as their first radiotherapy treatment than would be optimally recommended in this model. This suggests that many patients in New South Wales are not currently being referred for curative treatment.ConclusionPalliative radiotherapy is optimally recommended as the first course of radiotherapy in 14% of all newly diagnosed cancers.     

Squamous cell carcinoma of the anal canal at The Queen Elizabeth Hospital: A local experience

Aim: Concurrent chemoradiotherapy is the standard treatment for squamous cell carcinoma of anal canal. We describe our experience of treating such patients at our center. Methods: Patients with anal squamous cell carcinoma were treated with a uniform sphincter preserving protocol at The Queen Elizabeth Hospital, South Australia. Standard radiotherapy along with 5‐fluorouracil (750 mg/m² on days 1–5 and days 29–32) and mitomycin C (12 mg/m² on day 1 only) was given to eligible patients. Results: Of the 34 patients included in this study, nearly 60% were women. Most (89.3%) had T1‐2 disease. One‐third had nodal involvement. Twenty‐seven had chemoradiotherapy, six had local excision alone and one had radiotherapy alone. Among those who had chemoradiation, 71.5% had a complete response and remained colostomy free until the last follow‐up. Most completed the treatment without major side‐effects. The 3 and 5‐year disease free survival rate was 62% and 53%, respectively. All patients who failed chemoradiation underwent salvage surgery with a median survival time of 32.5 months. Conclusion: Sphincter preservation is the goal for anal cancers. Chemoradiotherapy is an important modality to achieve this goal.     

Carcinomas of the Paranasal Sinuses and Nasal Cavity Treated With Radiotherapy at a Single Institution Over Five Decades: Are We Making Improvement?

PURPOSE: To compare clinical outcomes of patients with carcinomas of the paranasal sinuses and nasal cavity according to decade of radiation treatment. METHODS AND MATERIALS: Between 1960 and 2005, 127 patients with sinonasal carcinoma underwent radiotherapy with planning and delivery techniques available at the time of treatment. Fifty-nine patients were treated by conventional radiotherapy; 45 patients by three-dimensional conformal radiotherapy; and 23 patients by intensity-modulated radiotherapy. Eighty-two patients (65%) were treated with radiotherapy after gross total tumor resection. Nineteen patients (15%) received chemotherapy. The most common histology was squamous cell carcinoma (83 patients). RESULTS: The 5-year estimates of overall survival, local control, and disease-free survival for the entire patient population were 52%, 62%, and 54%, respectively. There were no significant differences in any of these endpoints with respect to decade of treatment or radiotherapy technique (p > 0.05, for all). The 5-year overall survival rate for patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s was 46%, 56%, 51%, 53%, and 49%, respectively (p = 0.23). The observed incidence of severe (Grade 3 or 4) late toxicity was 53%, 45%, 39%, 28%, and 16% among patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s, respectively (p = 0.01). CONCLUSION: Although we did not detect improvements in disease control or overall survival for patients treated over time, the incidence of complications has significantly declined, thereby resulting in an improved therapeutic ratio for patients with carcinomas of the paranasal sinuses and nasal cavity.     

Primary radiotherapy versus radical prostatectomy for high-risk prostate cancer: a decision analysis

BACKGROUND:

Two evidence‐based therapies exist for the treatment of high‐risk prostate cancer (PCA): external‐beam radiotherapy (RT) with hormone therapy (H) (RT + H) and radical prostatectomy (S) with adjuvant radiotherapy (S + RT). Each of these strategies is associated with different rates of local control, distant metastasis (DM), and toxicity. By using decision analysis, the authors of this report compared the quality‐adjusted life expectancy (QALE) between men with high‐risk PCA who received RT + H versus S + RT versus a hypothetical trimodality therapy (S + RT + H).

METHODS:

The authors developed a Markov model to describe lifetime health states after treatment for high‐risk PCA. Probabilities and utilities were extrapolated from the literature. Toxicities after radiotherapy were based on intensity‐modulated radiotherapy series, and patients were exposed to risks of diabetes, cardiovascular disease, and fracture for 5 years after completing H. Deterministic and probabilistic sensitivity analyses were performed to model uncertainty in outcome rates, toxicities, and utilities.

RESULTS:

RT + H resulted in a higher QALE compared with S + RT over a wide range of assumptions, nearly always resulting in an increase of >1 quality‐adjusted life year with outcomes highly sensitive to the risk of increased all‐cause mortality from H. S + RT + H typically was superior to RT + H, albeit by small margins (<0.5 quality‐adjusted life year), with results sensitive to assumptions about toxicity and radiotherapy efficacy.

CONCLUSIONS:

For men with high‐risk PCA, RT + H was superior to S + RT, and the result was sensitive to the risk of all‐cause mortality from H. Moreover, trimodality therapy may offer local and distant control benefits that lead to optimal outcomes in a meaningful population of men. Cancer 2012;. © 2011 American Cancer Society.     

Gemcitabine and radiotherapy plus cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer: Long-term cumulative results of 2 prospective single-institution studies

BACKGROUND:

Cystectomy is the standard treatment for patients with infiltrating bladder cancer, but conservative treatment with cystoscopic resection followed by radiochemotherapy may be an alternative for highly selected patients. The addition of gemcitabine to cisplatin and radiotherapy may enhance disease control.

METHODS:

The long‐term clinical outcomes of 26 patients enrolled in a previously published dose‐finding study and a prematurely discontinued phase 2 trial were evaluated. All the patients underwent transurethral tumor resection followed by a radical dose of external radiotherapy administered at the same time as cisplatin and weekly gemcitabine therapy.

RESULTS:

After a median follow‐up of 74 months, the projected 5‐year clinical outcomes were a 70.1% overall survival rate, a 78.9% disease‐specific survival rate, and a 73.8% bladder‐intact survival rate.

CONCLUSIONS:

The long‐term follow‐up data from the current study confirmed that the addition of gemcitabine to radiotherapy and cisplatin is safe and leads to good local and distant disease control. The concomitant administration of cisplatin may explain the good long‐term organ preservation that was observed. Conducting confirmatory and comparative trials could satisfy an unmet need but requires the multidisciplinary cooperation of urologists in selecting the right patients for a bladder‐sparing strategy. Cancer 2011. © 2010 American Cancer Society.     

A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG)

Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow‐up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa‐associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty‐five per cent of the patients were female. The median age at diagnosis was 62 (range 28–88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression‐free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long‐term disease‐free survival for patients with localized disease. Systemic treatment, including alkylating‐containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright © 2015 John Wiley & Sons, Ltd.     

Survival of patients with hepatobiliary tract and duodenal cancer sites in Germany and the United States in the early 21st century

Hepatobiliary tract cancers (HBTCs) are a heterogeneous group of cancers with high mortality. Because most of these cancers, with the exception of hepatocellular carcinoma (HCC), are rare, few data are available concerning the population level survival expectations of patients with HBTC. Here, we describe survival of patients with HBTC in Germany with comparison to survival in the US. Therefore, data were extracted from 12 databases in Germany and the Surveillance, Epidemiology and End Results (SEER13) database in the US. Period analysis and modeled period analysis were used to calculate 5‐year relative survival estimates for patients with HBTC diagnosed from 1997 to 2013. HCC was the most common HBTC in each database, accounting for over 1/3 of HBTC in Germany and about half of cases in the US. Overall age adjusted 5‐year relative survival for HBTC in 2006‐2013 was 19.1% in Germany and 20.6% in the US. Five‐year relative survival increased by 3.8% units in Germany and 4.5% units in the US between 2002–2005 and 2010–2013. Five‐year relative survival for individual types of HBTC ranged from 9.8% in Germany and 2.9% in the US for not otherwise specified biliary tract cancers to 44.4% and 50.1%, respectively, in Germany and the US for duodenal cancers. In conclusion, survival for HBTC remains poor in both Germany and the US, although a small increase in survival in the past decade was observed. Further work to find better treatment options for HBTC is needed to improve survival.     

Impact of deprivation and rural residence on treatment of colorectal and lung cancer

For common cancers, survival is poorer for deprived and outlying, rural patients. This study investigated whether there were differences in treatment of colorectal and lung cancer in these groups. Case notes of 1314 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. On univariate analysis, the proportions of patients receiving surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and rural categories. Adjusting for disease stage, age and other factors, there was less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95% confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and treatment also appeared similar in all socio-economic and rural groups. Adjusting for disease stage and other variables, times to lung cancer treatment remained similar, but colorectal cancer treatment was quicker for outlying patients (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These findings suggest that socio-economic status and rurality may have a minor impact on modalities of treatment for colorectal and lung cancer, but do not lead to delays between referral and treatment.     

Estimating the demand for radiotherapy from the evidence: A review of changes from 2003 to 2012

Background and Purpose

In 2003 we estimated that 52.3% of new cases of cancer in Australia had an indication for external beam radiotherapy at least once at some time during the course of their illness. This update reviews the contemporary evidence to define the optimal proportion of new cancers that would benefit from radiotherapy as part of their treatment and estimates the changes to the optimal radiotherapy utilisation rate from 2003 to 2012.

Materials and Methods

National and international guidelines were reviewed for external beam radiotherapy indications in the management of cancers. Epidemiological data on the proportion of new cases of cancer with each indication for radiotherapy were identified. Indications and epidemiological data were merged to develop an optimal radiotherapy utilisation tree. Univariate and Monte Carlo simulations were used in sensitivity analysis.

Results

The overall optimal radiotherapy utilisation rate (external beam radiotherapy) for all registered cancers in Australia changed from 52.3% in 2003 to 48.3% in 2012. Overall 8.9% of all cancer patients in Australia have at least one indication for concurrent chemo-radiotherapy during the course of their illness.

Conclusions

The reduction in the radiotherapy utilisation rate was due to changes in epidemiological data, changes to radiotherapy indications and refinements of the model structure.     

Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities

Background:

Cancer of unknown primary (CUP) is the fourth most common cause of cancer death. With advanced diagnostics and treatments, we investigated the proportion of cancers diagnosed as CUP, treatment outcomes and association with socioeconomic disparities.

Methods:

We analysed trends in CUP diagnosis and outcome within the Surveillance, Epidemiology, and End Results registry between 1973 and 2008.

Results:

The percentage of all cancers diagnosed as CUP has decreased over time comprising <2% of cancers since 2007. A higher proportion of CUP was diagnosed in the elderly, females, blacks and residents of less affluent or less educated counties. Median survival of all CUP patients was 3 months, with no improvement over time. The 5-year survival significantly improved in those with squamous histology (squamous cell carcinoma; SCC) but only marginally in non-SCC. Factors associated with a longer survival on multivariate analysis included white race; female; <65 years old; most recent decade at diagnosis; SCC; married; a histological diagnosis; and treatment with radiotherapy (all P<0.001). Despite the improvement in survival with radiotherapy, its use was less frequent in females and blacks.

Conclusion:

The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SCC CUP. However, significant socioeconomic disparities exist in diagnosis and survival, suggesting inequalities in access to diagnostic investigations and treatment.     

Treatment and survival from colorectal cancer: the experience of patients at South Australian teaching hospitals between 1980 and 2002

AimsTo evaluate trends in colorectal cancer survival and treatment at South Australian teaching hospitals and degree of adherence to treatment guidelines which recommend adjuvant chemotherapy for Dukes' C colon cancers and combined chemotherapy and radiotherapy for high-risk rectal cancers.Materials and methodsTrends in disease specific survival and primary treatment were analysed, and comparisons drawn between diagnostic epochs, using cancer registry data from South Australian teaching hospitals. Statistical methods included univariate and multivariable disease specific survival analyses.ResultsFive-year survival increased from 48% in 1980–1986 to 56% in 1995–2002. Largest gains were for stage C, where survivals were higher when chemotherapy was part of the primary treatment. By comparison, gains in 1-year survival were largest for stage D. Chemotherapy was provided for 4% of patients with colorectal cancers in 1980–1986, increasing to 32% in 1995–2002. Among stage C cases below 70 years at diagnosis, the proportion having chemotherapy increased to 83% in 1995–2002. The most common chemotherapy was fluorouracil (5FU) as a single agent in 1980–1986 and 5FU with leucovorin in 1995–2002. As expected, radiotherapy was used more frequently for rectal than colon cancers, and particularly for stage C. Among stage C rectal cases below 70 years, the proportion having radiotherapy increased from 10% in 1980–1986 to 57% in 1995–2002. Approximately 93% of colorectal cancers were treated surgically. Patients not treated surgically tended to be aged 80 years or more and to present with distant metastases.ConclusionsTrends in chemotherapy and radiotherapy accord with evidence-based recommendations. There have been reassuring gains in survivals after adjusting for stage, grade and other prognostic indicators. The data show survival gains and treatment patterns that individual hospitals can use as benchmarks when evaluating their own experience.     

Molecular Targets in Biliary Carcinogenesis and Implications for Therapy

Biliary tract cancers (BTCs) encompass a group of invasive carcinomas, including cholangiocarcinoma (intrahepatic, perihilar, or extrahepatic), and gallbladder carcinoma. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. The latest recommendation is to treat advanced or metastatic disease with gemcitabine and cisplatin, although chemotherapy has recorded modest survival benefits. Comprehension of the molecular basis of biliary carcinogenesis has resulted in experimental trials of targeted therapies in BTCs, with promising results. This review addresses the emerging role of targeted therapy in the treatment of BTCs. Findings from preclinical studies were reviewed and correlated with the outcomes of clinical trials that were undertaken to translate the laboratory discoveries.

Implications for Practice:

Biliary tract cancers are rare. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. Median overall and progression-free survival are 12 and 8 months, respectively. Because chemotherapy has recorded modest survival benefits, targeted therapies are being explored for personalized treatment of these cancers. A comprehensive review of targeted therapies in biliary tract cancers was undertaken to present emerging evidence from laboratory and/or molecular studies as they translate to clinical trials and outcomes. The latest evidence on this topic is presented to clinicians and practitioners to guide decisions on treatment of this disease.     

Faculty of Radiation Oncology Position Paper on the use of Image–Guided Radiation Therapy

The development of technology such as intensity‐modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and stereotactic ablative body radiotherapy (SABR) has resulted in highly conformal radiotherapy treatments. While such technology has allowed for improved dose delivery, it has also meant that improved accuracy in the treatment room is required. Image‐guided radiotherapy (IGRT), the use of imaging prior to or during treatment delivery, has been shown to improve the accuracy of treatment delivery and in some circumstances, clinical outcomes. Allied with the adoption of highly conformal treatments, there is a need for stringent quality assurance processes in a multidisciplinary environment. In 2015, the Royal Australian and New Zealand College of Radiologist (RANZCR) updated its position paper on IGRT. The draft document was distributed through the membership of the Faculty of Radiation Oncology (FRO) for review and the final version was endorsed by the board of FRO. This article describes issues that radiotherapy departments throughout Australia and New Zealand should consider. It outlines the role of IGRT and reviews current clinical evidence supporting the benefit of IGRT in genitourinary, head and neck, and lung cancers. It also highlights important international publications which provide guidance on implementation and quality assurances for IGRT. A set of key recommendations are provided to guide safe and effective IGRT implementation and practice in the Australian and New Zealander context.     

Impact of Prior Local Treatment on the Outcomes of Metastatic Hormone-Sensitive Prostate Cancer: Secondary Analysis of a Randomized Controlled Trial

Background

Local treatment of metastatic prostate cancer and its impact on future disease course requires further assessment. We sought to evaluate the impact of prior local treatment to the prostate on the outcomes of hormone-sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study.

Survival advantage for prostate cancer patients treated with high-dose three-dimensional conformal radiotherapy.

PURPOSE: The value of treating prostate cancer has been questioned, and some insist that a survival benefit is demonstrated to justify treatment. Prospective dose-escalation studies with three-dimensional conformal radiotherapy technique have demonstrated improvement in biochemical freedom from disease and local control. We report the outcomes of high-dose treatment with three-dimensional conformal radiotherapy compared with low-dose treatment for biochemical freedom from disease, freedom from distant metastasis, cause-specific survival, and overall survival. PATIENTS AND METHODS: The study design was retrospective, involving pairs matched on independent prognostic variables in which each patient treated with low-dose radiotherapy was matched with a patient treated with high-dose radiotherapy. Outcomes were compared for two groups of patients: Group I: Three-dimensional conformal radiotherapy treatment--296 patients treated with more than 74 Gy matched on stage, grade, and prostate-specific antigen level, to 296 patients treated with less than 74 Gy. Group II: Three-dimensional conformal radiotherapy treatment--357 patients treated with more than 74 Gy matched on stage and grade to 357 patients treated with less than 74 Gy. RESULTS: Univariate analysis showed that dose is a significant predictor of biochemical freedom from disease, freedom from distant metastasis, and cause-specific survival for group I and biochemical freedom from disease, freedom from distant metastasis, cause-specific survival, and overall survival for group II. Multivariate analysis showed that dose is a significant independent predictor in group I for biochemical freedom from disease and freedom from distant metastasis and for biochemical freedom from disease, freedom from distant metastasis, cause-specific survival, and overall survival in group II. DISCUSSION: These data provide strong support for the definitive treatment of prostate cancer with high-dose (> 74 Gy) three-dimensional conformal radiotherapy. These doses can be safely delivered with three-dimensional conformal radiotherapy techniques. Various institutions and industry must collaborate to expand the technology allowing the use of high-dose three-dimensional conformal radiotherapy in the national practice beyond centers of technological excellence.