Primary tumor

Radiotherapy to the Primary Tumor for Newly Diagnosed Metastatic Prostate Cancer

Posted by

0


TAKE-HOME MESSAGE

  • This phase III trial was designed to evaluate the benefit of radiotherapy to the primary tumor in patients with newly diagnosed metastatic prostate cancer. Radiation to the primary tumor improved overall survival among patients with a low metastatic burden (fewer than four bone metastases and no visceral metastases) at baseline.
  • Radiation to the primary tumor did not improve overall survival in the entire study population.
This was a randomized phase III trial of 2061 men with newly diagnosed metastatic prostate cancer. Men were randomized 1:1 to standard of care or to standard of care plus radiation. All patients received lifelong androgen-deprivation therapy. The primary outcome was overall survival. Subgroup analysis consisted of disease burden as defined by CHAARTED, with high metastatic burden defined as four or more bone metastases, with one or more outside the vertebral bodies or pelvis, or visceral metastases, or both. This subgroup analysis was added to the protocol in May of 2018. The overall survival was not improved with the addition of radiotherapy to the prostate in the whole cohort. Looking at the low-volume subgroup, there was a survival advantage at 3 years (73% vs 81%; HR, 0.68; P=.007). There was also an improvement in prostate cancer–specific survival at 3 years (79% vs 86%; P=.65) in the low-volume subgroup. This is certainly an intriguing finding, but it needs to be appreciated that the metastatic burden subgroup was created in May of 2018. However, this subgroup was specified prior to data analysis, and the determination of metastatic burden was used with pre-randomization imaging. Given a statistically significant survival advantage, it seems to be reasonable to provide radiation to the prostate to a select group of men with low-volume disease.

abstract

This abstract is available on the publisher’s site.

BACKGROUND

Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.

METHODS

We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule.

FINDINGS

Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63-73) and median amount of prostate-specific antigen of 97 ng/mL (33-315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3-4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy).

INTERPRETATION

Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.

Endoscopic evaluation of primary tumor response in patients with metastatic colorectal cancer treated by systemic chemotherapy.

Posted by

0


Abstract

Background

The number of cases of metastatic colorectal cancer treated by chemotherapy without primary tumor resection has recently increased. However, evaluation of primary tumor response by computed tomography is difficult in such cases. In this study, the usefulness of evaluation of primary tumor response to chemotherapy by endoscopy was investigated.

Methods

This retrospective analysis was performed at the Shizuoka Cancer Center and included 31 patients (88 evaluations) with metastatic colorectal cancer. Computed tomography and endoscopy were performed concomitantly between September 2002 and June 2006. Patients were treated by systemic chemotherapy without prophylactic primary tumor resection. Definitions of primary tumor response were as follows: (1) complete response, confirmed by colorectal biopsy; (2) progressive disease, enlargement of at least one of five tumor parameters; and (3) neither (1) nor (2). Computed tomography was performed to evaluate primary tumor response according to the Response Evaluation Criteria in Solid Tumors and to identify colorectal stenosis secondary to primary tumors.

Results

The rate of concordance between endoscopy and computed tomography for evaluation of primary tumor response was 75 %. Colorectal stenosis was detected 14 times by endoscopy (9 cases) and 3 times by computed tomography (3 cases). Of the 7 patients in whom surgery was required, 6 exhibited stenotic symptoms before endoscopic detection.

 

Conclusions

With regard to primary tumor response evaluation, a high concordance rate was observed between endoscopy and computed tomography, although endoscopic evaluation appeared more sensitive in detecting colorectal stenosis requiring surgical treatment.

Source: International Journal of Clinical Oncology