Salvage radiotherapy in patients with persistently detectable PSA or PSA rising from an undetectable range after radical prostatectomy gives comparable results

Purpose

Salvage radiotherapy (SRT) is applied routinely in patients with a biochemical relapse after radical prostatectomy (RP). Although the detection threshold for relapse after RP has steadily been lowered, only about 30 % of the SRT patients achieve a durable response. We have previously shown the association between a PSA decrease below detectable levels after SRT and biochemical progression-free survival (BPFS). After recalculating our data according to a more recent definition of biochemical failure after SRT, we now show the significance of the post-RP PSA nadir.

Materials and methods

Among 159 prostate cancer patients without hormonal treatment after RP, SRT was given to 72 patients with persistently detectable PSA after RP and to 87 whose PSA increased out of an undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to the prostate bed.

Results

The overall median follow-up time was 41.7 months. The probability for BPFS after this period was 52.8 % in 72 patients with persistently detectable PSA after RP and 65.4 % in 87 patients who had a post-RP PSA nadir below detection limit. Univariate and multivariate analyses showed no significant difference in BPFS of both patient groups (p > 0.05).

Conclusion

Our findings suggest that SRT is a viable treatment option for patients with persistently detectable PSA, giving similar results as in patients whose PSA increases out of an undetectable range after RP.     

Phase 3 Study of Adjuvant Radiotherapy Versus Wait and See in pT3 Prostate Cancer: Impact of Pathology Review on Analysis

Background

In a randomised trial, radical prostatectomy (RP) followed by adjuvant radiotherapy (aRT) was compared with RP alone in patients with pT3 pN0 prostate cancer with or without positive margin at local pathology (German Cancer Society trial numbers ARO 96-02/AUO AP 09/95).

Objective

A pathology review was performed on 85% of RP specimens of patients to investigate the influence of pathology review on the analysis.

Design, setting, and participants

Patients post-RP (n = 385) were randomised before achieving an undetectable prostate-specific antigen (PSA) level to either wait and see (n = 192) or 60 Gy aRT (n = 193). Of 307 patients with undetectable PSA after RP, 262 had pathology review. These results were included prospectively into the analysis.

Outcome measurements and statistical analysis

Agreement between local and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic reliability for the different parameters was analysed by Cox regression model. Event-free rates were determined by Kaplan-Meier analysis with a median follow-up of 40 mo for the wait-and-see arm and 38.5 mo for the aRT arm.

Results and limitations

There was fair concordance between pathology review and local pathologists for seminal vesicle invasion (pT3c: 91%; κ = 0.76), surgical margin status (84%; κ = 0.65), and for extraprostatic extension (pT3a/b: 75%; κ = 0.74). Agreement was much less for Gleason score (47%; κ = 0.42), whereby the review pathology resulted in a shift to Gleason score 7. In contrast to the analysis of progression-free survival with local pathology, the multivariate analysis including review pathology revealed PSMs and Gleason score >6 as significant prognostic factors.

Conclusions

Phase 3 studies of postoperative treatment of prostate cancer should be accomplished in the future with a pathology review. In daily practice, a second opinion by a pathologist experienced in urogenital pathology would be desirable, in particular, for high-risk patients after RP.     

High dose rate brachytherapy of localized prostate cancer

OBJECTIVE: We evaluated the safety and efficacy of high dose rate (HDR) brachytherapy using Iridium-192 (Ir 192) and 3D conformal external beam radiotherapy in patients with localized prostate cancer. METHODS: A total of 444 patients with localized prostate cancer underwent combined radiotherapy with interstitial Ir 192 and 3D conformal external beam radiotherapy between December 1992 and March 2001. The 230 patients, treated between December 1992 and December 1997 were analyzed. All patients underwent laparoscopic pelvic lymph node dissection to exclude patients with lymphatic involvement. Ir 192 was delivered twice with a 1-week interval in HDR remote control technique. The interstitial dose from December 1992 to December 1993 was 10Gy, after December 1993 the dose was reduced to 9Gy per treatment session. The interstitial application was followed by external beam radiation of 45Gy for cT1-cT2 and 50.4Gy for cT3 tumor (40Gy from December 1992 to December 1993). Progression was defined as biochemical failure according to ASTRO criteria, e.g. three consecutive PSA rises following the PSA nadir. RESULTS: The median PSA value decreased from 12.8 to 0.93ng/ml 12 months after treatment. Median PSA value was 0.47 after 24 months, 0.30ng/ml after 36 months and 0.18ng/ml after 60 months. 68% of the biopsies were negative 24 months after therapy. Progression-free rate was 100% for cT1 tumors, 75% for cT2 and 60% for stage-cT3 on 5-year follow-up. Five-year overall survival was 93%, 5-year disease-specific survival was 98%. Initial PSA value <10ng/ml, low stage and low grade were significantly related to 5-year progression-free survival. CONCLUSIONS: Combined HDR brachytherapy with Ir 192 is an alternative treatment option especially for patients with cT3 prostate cancer. Initial PSA value, stage and grade, are important prognostic factors.     

Prehospital use of hypertonic solutions for traumatic brain injury

Hypertonic solutions efficaciously lower increased intracranial pressure and improve cerebral hemodynamics in particular at the level of microcirculation. Therefore hypertonic solutions have been introduced to the in-hospital intensive care treatment of brain-injured patients. In view of the disturbed cerebral perfusion and oxygenation in the acute phase following traumatic brain injury, early initiation of treatment is desirable to improve long-term outcome and to minimize secondary brain damage. Two different hypertonic isooncotic solutions are licensed in Germany for prehospital and in-hospital treatment of acute hypotension due to hypovolaemia and haemorrhagic shock. Both solutions offer interesting therapeutic options for treatment of patients with increased intracranial pressure. Limitation of license to the treatment of shock in Germany does not allow routine prehospital use in isolated head trauma at the moment. In other European countries, the approval for the prehospital use of hypertonic isooncotic solutions has been modified.     

Erfolgreiche präklinische Blutstillung mit Chitosan-Gaze

This article presents the case of a patient with haemorrhagic shock due to self-inflicted stab wounds to the chest and upper abdomen during a suicide attempt. Prehospital packing with chitosan gauze resulted in hemostasis and stabilisation of the patient during transport to the hospital. For uncontrolled bleeding from penetrating trauma the use of hemostyptic agents is an important option. The authors believe that hemostyptic agents should be introduced into clinical praxis of emergency medical services (EMS) and their use should be trained by EMS personnel.     

Radiotherapy of unilateral choroidal metastasis: unilateral irradiation or bilateral irradiation for sterilization of suspected contralateral disease?

Radiotherapy is the highly effective standard in the treatment of choroidal metastasis. Visual acuity can be stabilized or increased in about 70-80% of eyes treated, thus prevailing the quality of life in these worse prognostic patients. In about 30-40% bilateral macroscopic disease is found at diagnosis. The best treatment for unilateral metastasis remains controversial: unilateral or bilateral irradiation for sterilization of suspected contralateral metastasis or unilateral irradiation without irradiation of the contralateral choroidea. In the analysis of a prospective study (ARO 95-08) 35 out of 50 patients with choroidal metastasis had unilateral disease and received unilateral irradiation with a lateral field using 6 MeV-photons (40 Gy in 20 fractions) without sparing the contralateral choroidea. Therefore the posterior contralateral choroidea received 50-70% of the total dose (20-28 Gy) for suspected micrometastasis. None of these patients developed contralateral choroidal metastasis during the median follow up time of 11.5 months. A unilateral field with 40 Gy for unilateral choroidal metastasis without sparing the contralateral choroidea seems to be effective in destroying contralateral micrometastasis with a lower risk of late side effects compared with bilateral fields.