Serum PSA evaluations during salvage radiotherapy for post-prostatectomy biochemical failures as prognosticators for treatment outcomes.

INTRODUCTION: Serum prostate specific antigen (PSA) levels have proved to be sensitive markers for the diagnosis of prostate cancer. In addition, PSA levels are useful for detecting and monitoring prostate cancer progression after radiotherapy. Serum PSA evaluations during radiotherapy, however, have not been well documented. In this study, we investigate the prognostic value of PSA evaluations during salvage radiotherapy for prostatectomy failures. METHODS: Forty-one patients with biochemical failures after prostatectomy treated with salvage radiotherapy consented to have their serum PSA levels evaluated at 30 Gy and 45 Gy of irradiation. All 41 patients had negative metastatic workup and pathologically uninvolved pelvic lymph nodes at the time of referral for salvage radiotherapy. Radiation therapy was delivered with 10--25 MV photons, with doses of 59.4--66.6 Gy. No patients received hormonal ablation therapy before irradiation. RESULTS: The mean follow-up for all patients was 30.9 months. At last follow-up, 28/41 patients (68.3%) were free from biochemical failure, with 20 of 41 patients (48.8%) expressing undetectable PSA levels. Serum PSA evaluations at 30 Gy did not significantly predict for either biochemical (p = 0.0917) or clinical (p = 0.106) disease-free outcome. However, serum PSA evaluations at 45 Gy significantly predicted for both biochemical (p = 0.0043) and clinical (p = 0.0244) disease-free outcomes, with PSA elevations at 45 Gy significantly associated with poor outcomes. On univariate analysis of prognosticators for biochemical failures, the following were significant: an elevation in serum PSA levels at 45 Gy, detectable serum PSA immediately after prostatectomy, Gleason score 7--10, and serum PSA level >1 ng/ml before salvage radiotherapy. CONCLUSION: Evaluation of serum PSA level at 45 Gy of salvage radiotherapy for biochemical relapses after prostatectomy may serve as a significant prognosticator for both biochemical and clinical disease-free outcomes.

Spinal cord compression, infection, and unknown primary cancers.

The management of a patient with spinal cord compression can be complicated and challenging; however, this challenge becomes even more pronounced if the patient presents without a known cancer diagnosis in the context of progressive neurologic symptoms. Unless potential causes such as infection/tuberculosis are included in the differential diagnosis of an apparent unknown primary, then the correct diagnosis may be incorrectly determined.

Prostate-specific antigen-all that rises is not refractory.

After the initiation of androgen suppression in men with prostate cancer, the serum prostate-specific antigen (PSA) level generally declines. A subsequent PSA rise during that suppression usually reflects the presence of a significant component of hormonally refractory prostate cancer. We report a patient with a rising PSA level and elevated testosterone level after depot leuprolide in whom the PSA level subsequently declined with administration of bicalutamide.

High-grade carcinoma of the prostate: a comparison of current local therapies.

OBJECTIVES: To determine the impact of either single or combined local therapeutic modalities for poorly differentiated (Gleason score 8 to 10) prostate cancer. METHODS: Between 1987 and 1996, 156 patients were diagnosed with biopsy proven, poorly differentiated (Gleason score 8 to 10), clinically localized prostate cancer. Of these patients, 87 were treated with radical prostatectomy alone, 19 with radiotherapy, and 24 with both prostatectomy and postoperative radiotherapy. RESULTS: The median follow-up time was 74.6 months. The 5-year biochemical progression-free survival (PFS) for patients with a Gleason score of 8 to 10 was 65%, 30%, and 20% for patients treated with surgery plus postoperative radiotherapy, radiotherapy alone, and surgery alone, respectively (P <0.0001 between postoperative radiotherapy and all other groups, P = 0.6131 between surgery and radiotherapy). The 5-year clinical PFS was 80%, 60%, and 35% for patients treated with surgery plus postoperative radiotherapy, radiotherapy alone, and surgery alone (P <0.0001 between postoperative radiotherapy and all others, P = 0.1975 between surgery and radiotherapy). The independent prognosticators for biochemical failure included serum prostate-specific antigen level greater than 20 ng/mL and seminal vesicle invasion; only seminal vesicle invasion was prognostic for clinical failure. CONCLUSIONS: Patients with high-grade prostate cancer (Gleason score 8 to 10) have uniformly poor, but apparently similar, biochemical and clinical PFS rates when treated by either prostatectomy or radiotherapy alone. The addition of postoperative radiotherapy in the treatment of these patients may be associated with improved biochemical and clinical PFS compared with either modality alone.

Subclinical disease revisited.

It has become commonplace to treat postoperative patients with adjuvant radiotherapy to increase local control. The reduction in local recurrences seen in patients with head and neck cancer following radiotherapy led to coining of the term "subclinical disease" to describe the presumed presence of small, clinically undetectable, nests of tumor cells which remain even after the most aggressive of surgeries. The basic assumption fundamental to the concept of subclinical disease is that any patient with residual disease will suffer a local failure if left untreated. For example, lymph node involvement, either clinically evident or pathologically proven, is considered an absolute indication for adjuvant therapy. A positive or "close" or "microscopically positive" margin is also considered grounds for further treatment. The purpose of this communication is to critically discuss recent reports that challenge this assumption.

Assessment of relative tumor burden in patients with clinical T1c prostate cancer treated with either external beam or radical prostatectomy.

The choice between external beam radiation therapy (EBRT) or retropubic radical prostatectomy (RPX) as potentially curative treatment for localized carcinoma of the prostate gland (CaP) has not been delineated in randomized studies. Both treatments are more effective if tumor burden is low. We sought to compare these two treatments in patients who had clinical stage T1c (cT1c) lesions and who were thought to have limited tumor burdens pretreatment. Sixty cT1c patients referred to the Department of Radiation Oncology received 66 Gy in 33 sessions of EBRT to localized prostate ports and 59 cT1c patients had RPX. No neoadjuvant nor early adjuvant therapies were prescribed. Radiotherapy success was defined biochemically as a nonrising prostate-specific antigen (PSA) of +/- 1.5 ng/ml. RPX success required a postoperative PSA that was undetectable (PSA <0.2 ng/ml by the Hybritech or Abbott IMx technics). Analysis for nonrising posttreatment PSA levels was performed using Kaplan-Meier and Cox regression methods. Mantel-Haenszel methods were used to determine odds ratios for treatment groups adjusting for potential confounders. We ultimately assessed the relative tumor burden by histologic examination of the RPX specimens. The two treatment groups, although not randomized, were statistically similar in biopsy Gleason Scores, transrectal ultrasonography calculated gland volumes, number of positive biopsy cores, and estimated amount of cancer identified on initial biopsies. Pathologic stage T3 was identified in 25% of RPX patients. Fifty to 60% of RPX specimens histologically had substantial tumor burden and by inference also the EBRT patients. At a median follow-up (F/U) of 36 months, 76% of RPX patients maintained an undetectable PSA, whereas 62% of EBRT patients had a PSA < 1.5 ng/ml at a median F/U of 29 months. The pretreatment PSA values significantly affected EBRT patients' risk of a rising posttreatment PSA level. Twenty-four months after treatment, RPX patients were 3.7 times more likely to maintain a nonrising PSA level (RPX patients posttreatment PSA < 0.2 ng/ml), than EBRT patients (posttreatment PSA < or = 1.5 ng/ml) (p = 0.006). Sixty-six gray in 33 sessions to localized EBRT ports is not sufficiently aggressive therapy for one third or more of patients with cT1c CaP. RPX alone is insufficient therapy for one fourth of cT1c patients. Analysis of the RPX specimens showed that many cT1c tumors have a significant tumor burden. Selection methodologies to separate out patients who require more than conventional dose or type of radiotherapy or more than RPX as monotherapy are needed. Pretreatment PSA and number of positive biopsies may assist this selection process.

Radiation therapy port films: a quality assurance study.

PURPOSE: The purpose of this study was to assess the port film acceptance rate in a large community practice setting and to catalog the reasons for rejection. METHODS: Between December 1993 and July 1996, a quality assurance monitor log was maintained on 4,150 patients who underwent a total of 4,450 treatment courses. Port films were taken at the beginning and at the half way point in the treatment course. A total of 20,735 port films were compared with the matching simulation films. We recorded the site being treated, the radiation oncologist who reviewed the films and the reason for rejection. RESULTS: The monthly acceptance rate varied from a low of 67% to a high of 83%, with a gradual upward trend. The single most common reason for rejecting films was a centering problem-12% of all films taken were rejected for this reason. The next most common problems were block placement or body setup errors that caused 3.4% and 2.7% of the films to be rejected, respectively. Average acceptance rates between 10 different sites (abdomen, brain, breast, chest, extremities, head and neck, pelvis, prostate, rectum and spine) varied from 68% to 80%. Individual differences between 12 radiation oncologists reviewing the films varied from 67% to 87%. CONCLUSIONS: A detailed analysis of field localization errors allowed us to identify areas where improvement was needed and suggested that specific guidelines for acceptance would help reduce the variability noted in the acceptance rate between sites and physicians.

The final report of the expert panel for the radiation oncology bone metastasis work group of the American College of Radiology.

BACKGROUND: In the United States, at least half of the patients who are irradiated are done so with palliative intent. The most common presentation is the patient with bone metastasis. However, because current scientific outcome and technology techniques are insufficient for the creation of guidelines, the American College of Radiology created a work group of experts to formulate appropriateness criteria for the irradiation of bone metastasis. METHOD: A MEDLINE search to help review the community practices was initiated. Twenty-five clinical vignettes were reviewed by a panel of experts. Recommendations for each vignette were prioritized and selected based on choices proposed by panel members. RESULT: Doses in the range of 20 Gy in 5 fractions, 30 Gy in 10 fractions, or 35 Gy in 14 fractions are acceptable in most circumstances. Daily doses > 4.0 Gy were not commonly suggested. CIRCUMSTANCES: To determine optimal dose fractionation schemes, more emphasis needs to be put on the life expectancy of the patients. Rapid schedules are acceptable in patients with short life expectancy (i.e., < 3 months), but this hypothesis needs to be tested. Further research to better define the clinical indications of hemibody irradiation and strontium-89 is recommended.

Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal.

PURPOSE: To determine the efficacy and tolerance of a standardized protocol of chemotherapy and low-dose radiotherapy in the treatment of anal cancer in human immunodeficiency virus (HIV)-infected patients. METHODS AND MATERIALS: Between 1987 and 1995, eight HIV-positive patients with squamous cell carcinoma of the anal canal, four of whom had acquired immunodeficiency syndrome (AIDS), received therapy at the Kaiser Permanente Medical Center. All patients were treated using a combined modality approach consisting of low-dose radiotherapy (30 Gy in 15 fractions delivered 5 days/week), and chemotherapy [1000 mg/m2 of 5-fluorouracil (5-FU) delivered on days 1-4 and 29-32 as a continuous infusion over 96 h, and 10 mg/m2 of mitomycin C delivered as a bolus injection on day 1]. Patients have been followed from 4 to 81 months (mean 41, median 38). RESULTS: All eight patients completed the therapy with minor variations to the protocol, and all have attained a clinical complete response. Four patients are alive and free of disease, and four died as a result of complications of AIDS, but remained free of anal carcinoma. There were no mortalities from the protocol and the morbidity was acceptable. Only one patient each was noted to have Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 4 hematologic and gastrointestinal acute toxicity, and no Grade 4 skin toxicity was noted. CONCLUSION: This combined therapy is effective for HIV-infected patients and appears to be tolerable with acceptable toxicities. It is best applied to patients who are HIV positive, or who have AIDS without concurrent major opportunistic infections. This approach is reasonable and affords patients a reasonably good chance at sphincter preservation by avoiding abdominoperineal resection. The optimal therapy for HIV-positive patients with advanced AIDS remains less well defined.

The need for individualized dosimetry for tangential breast treatment.

We have examined the isodose distributions of 119 intact breast patients treated on a 6 MV linac to determine if a library of treatment plans could be used instead of individualized computer plans for patient treatments without compromising the quality of those treatments. The parameters studied were: field width, baseline separation, central axis separation, wedge angle, and isodose coverage. At least two wedges were used in the computer plans for each patient and the best plan was then chosen. In order to construct a library of plans, the choice of wedge, treatment isodose, and dose uniformity should be predictable. Our results show that for 90 out of 119 plans (76%), the 30 degrees wedge was best. In the other 29 cases, either the 15 degrees or the 45 degrees wedge yielded better plans. On average, the improvement in dose homogeneity due to choice of wedge was about 2% (range 0-7%) for these cases. Although grouping like-patient parameters generally restricted the isodose variation to +/- 2.5%, there were five patients for which up to a 7% underdosage would not have been predicted. For the set of plans using a 30 degrees wedge, a significant correlation was found for the ratio of the baseline to central axis separation vs. treatment isodose. The average isodose which covered the target area was 97% (range 90-100%) and 102 out of 107 patient plans using the 30 degrees wedge fell between 94 and 100%. We conclude from these results that the variation in dose distribution found with seemingly similar sized breasts is due to the variation in breast shape and symmetry. The use of a library plan with a single wedge and a standardized isodose line for tangential field treatment of intact breast could cause up to a 7% dose difference compared to the actual dosimetry for that patient.