Ralph J. Miller

Ten-year biochemical disease control for patients with prostate cancer treated with cryosurgery as primary therapy.

OBJECTIVESnProstate cryosurgery has been increasingly used for the management of localized prostate cancer since its introduction in a minimally invasive form in the early 1990s. We performed a retrospective study of the largest and most mature patient group treated with cryosurgery reported thus far.nnnMETHODSnWe retrospectively analyzed the data from 370 patients treated consecutively from 1991 to 1996 with a focus on the determination of biochemical disease-free survival for a group of patients with T1 to T3 prostate cancer who had undergone prostate cryosurgery as primary monotherapy. Only patients with no previous radiotherapy, hormonal therapy, or surgery were included.nnnRESULTSnThe median follow-up was 12.55 years. Using a nadir plus 2 ng/dL definition, Kaplan-Meier analysis demonstrated a biochemical disease-free survival rate at 10 years of 80.56%, 74.16%, and 45.54% for low, moderate, and high-risk groups, respectively. The 10-year negative biopsy rate was 76.96%.nnnCONCLUSIONSnThe results for this pilot group of patients who underwent percutaneous prostate cryosurgery monotherapy demonstrated biochemical disease-free survival rates that overlap with those of similar groups of patients treated under similar circumstances using other types of nonextirpative monotherapy.

Cryosurgical ablation of the prostate: two-year prostate-specific antigen and biopsy results.

OBJECTIVESnPercutaneous cryosurgical ablation of the prostate (CSAP) was performed on patients with localized or locally advanced adenocarcinoma of the prostate. To assess local disease control, post-treatment biopsy and serum prostate-specific antigen (PSA) levels were obtained at 3 and 24 months post-treatment.nnnMETHODSnFrom June 1990 through May 1994, CSAP was performed 448 times on 383 patients under Institutional Review Board protocols. A urethral warming catheter was used for all procedures. A total of 239 patients were followed for a minimum of 21 months after treatment. None of this group had received prior local treatment. The group consisted of patients who were newly diagnosed and treated solely with cryotherapy (virgin); the remainder had been on androgen deprivation therapy (ADT) prior to CSAP.nnnRESULTSnBiopsies were obtained from 114 patients at 21 months or more after treatment. In the virgin group, 79% had a negative biopsy after one or more treatments, and 88% of the ADT group are negative after one or more treatments. Overall, 69% had a negative biopsy after one treatment and 82% had a negative biopsy following one or more CSAP treatments. Of a group of 163 patients, PSA data were evaluable at 21 months or more after treatment. In the virgin group, 60% had a PSA 0.4 ng/mL or less, and 77% had a PSA 1.0 ng/mL or less. In the ADT group, 40% had a PSA 0.4 ng/mL or less, and 69% had a PSA value of 1.0 ng/m Lor less. Complications were minimal, the most common one being urethral tissue sloughing, which occurred in 10% of patients.nnnCONCLUSIONSnCSAP appears to be effective in obtaining local control as measured by biopsy and PSA 21 months or more post-treatment. When retrospectively comparing our results with recently published radiotherapy series, CSAP was more effective in obtaining nadir PSA values 1.0 ng/mL or less and negative biopsies at 21 months or more after treatment.

Urethral warming catheter for use during cryoablation of the prostate

Cryoablation of the prostate has been shown to be a useful tool in the eradication of prostate cancer. Sloughing of necrotic tissue per urethra was one of the major complications of prostate cryosurgery during its initial application and led to its disuse by urologists. A catheter was then needed until sloughing was complete and the patient again able to void. In a previous report, we have demonstrated that thermal protection of the urethra could be obtained by flowing warm irrigant through a thin-walled urethral conduit. To simplify the application of this heat, a dual lumen urethral catheter has been designed that can be passed transurethrally to circulate warm saline and prevent the destruction of the urethral epithelium. This prevents transmural necrosis, maintaining the epithelial barrier for containment of necrotic prostate tissue after treatment. This urethral warming device is made of materials commonly found in operative stockrooms. To date, the device has functioned well with a urethral sloughing rate of 12% during its initial use.

Salvage radiotherapy for prostate cancer recurrence after cryosurgical ablation.

OBJECTIVESnTo retrospectively determine the outcome of patients treated with salvage three-dimensional conformal radiotherapy (RT) for prostate cancer recurrence after cryosurgical ablation of the prostate (CSAP). Biochemical control rates and morbidity were analyzed.nnnMETHODSnBetween January 1990 and November 1999, a total of 49 patients initially treated with CSAP were later irradiated because of a rising prostate-specific antigen (PSA) level and/or a positive biopsy at Allegheny General Hospital. The clinical stage before cryosurgery was T1c in 7 patients; T2a in 7 patients; T2b in 10 patients; T3 in 17 patients; and T4 and/or N1 in 8 patients. The Gleason score was 6 or lower in 29 patients, 7 in 11 patients, and 8 or higher in 9 patients. The mean pre-CSAP PSA level was 15.7 ng/mL (range 2.4 to 45). One patient had a PSA level less than 4 ng/mL, 16 had a PSA level of 4 to 10 ng/mL, 21 had a PSA level of 10 to 20 ng/mL, and 11 had a PSA level greater than 20 ng/mL. Before the start of RT, a complete restaging workup was performed and was negative for distant metastatic disease in all 49 patients. The mean interval to recurrence after CSAP was 19 months (range 3 to 78). The mean RT dose to the planning target volume was 62.9 Gy (range 50.4 to 68.4).nnnRESULTSnThe mean pre-RT PSA level was 2.4 ng/mL (range 0.1 to 7.4). After RT, the mean nadir PSA level was 0.4 ng/mL (range 0 to 4.2). The mean time to PSA nadir was 5.8 months (range 1 to 15). In 42 patients, the PSA nadir was less than 1.0 ng/mL, in 5 patients the PSA nadir was greater than 1 ng/mL, and in 2 patients the PSA level remained stable. With a median follow-up time of 32 months (range 12 to 85), the overall biochemical control rate was 61%. The mean time to biochemical failure was 14.5 months (range 1 to 47). Of 30 patients with a pre-RT PSA level of 2.5 ng/mL or less, the disease of 22 (73%) was controlled compared with only 8 (42%) of 19 with a pre-RT PSA level greater than 2.5 ng/mL (P = 0.040). Biochemical control occurred in 18 (69%) of 26 patients with a dose of 64 Gy or greater compared with only 12 (52%) of 23 patients with a dose of less than 64 Gy (P = 0.024). The disease of 20 (70%) of 29 patients with a Gleason score of 6 or lower was controlled versus 10 (50%) of 20 patients with a Gleason score of 7 or greater (P = 0.064). Only 2 patients developed subacute morbidity (proctitis and a urethral stricture). All complications resolved with conservative measures.nnnCONCLUSIONSnSalvage RT for prostate cancer recurrence after CSAP appears feasible. Our preliminary experience revealed that post-CSAP RT in patients with prostate cancer appears to effectively diminish the post-RT PSA level to a nadir of 1.0 ng/mL or less in most patients. The pre-RT PSA level and radiation dose may be important predictors of biochemical control in the salvage setting. RT as described was associated with minimal toxicity to the gastrointestinal/genitourinary systems. Additional prospective randomized studies are necessary to better assess the role of RT in the treatment of these patients.

Multidisciplinary treatment of synchronous primary rectal and prostate cancers

Background A 58-year-old Caucasian man with a history of irritable bowel syndrome and occasional rectal bleeding presented with a 4-week history of progressive, bright red blood per rectum. A digital rectal examination revealed a 3 cm distal, midrectal mass. Laboratory tests showed an elevated serum prostate-specific antigen of 32 ng/ml but other physical and medical examinations were unremarkable.Investigations Digital rectal examination, colonoscopy, rectal mass biopsy, endorectal ultrasound, transrectal ultrasound-guided prostate biopsy, CT scan and MRI.Diagnosis Clinical stage III (T3N1M0), moderately differentiated adenocarcinoma of the rectum and clinical stage II (T1cN0M0) adenocarcinoma of the prostate.Management Intensity-modulated radiation therapy, chemoradiation, chemotherapy, hormone therapy and surgery.

Cryosurgical ablation of the prostate: treatment alternative for localized prostate cancer

In 1995, an estimated 244,000 new cases of adenocarcinoma of the prostate will be diagnosed, making it the most common malignant tumor in men [1]. Widespread screening has lead to increased detection of prostate cancer with the aid of prostate-specific antigen, transrectal ultrasound, increased media attention and a rapidly expanding elderly population.

Combination of IG-IMRT and permanent source prostate brachytherapy in patients with organ-confined prostate cancer: GU and GI toxicity and effect on erectile function

PURPOSEnTo assess toxicity outcomes of image-guided intensity-modulated radiation therapy (IG-IMRT) combined with permanent prostate seed implant in a cohort of patients with localized prostate cancer.nnnMETHODS AND MATERIALSnA retrospective analysis was performed on 67 patients with the median pretreatment prostate-specific antigen level of 5.4. The Gleason score was less than 7 in 7 patients, 7 in 52 patients, and greater than 7 in 8 patients. The median followup was 28.2 months (range, 12-89.5 months). Treatment consisted of 45 (n=65) or 50.4 Gy (n=2) at 1.8 Gy/fraction of IG-IMRT to the prostate and seminal vesicles. Eight patients had simultaneous irradiation of pelvic lymph nodes to 45 (n=65) or 50.4 Gy (n=2). After IG-IMRT, patients received transperineal prostate implant boost with either (103)Pd (n=65, the prescribed D(90) of 100 Gy) or (125)I (n=2, D(90) of 110 Gy). Eleven patients received androgen deprivation therapy with radiotherapy.nnnRESULTSnToxicity higher than Grade 3 was not observed. The combined incidence of acute and late Grade 3 genitourinary toxicity was 6%. The combined incidence of acute and late Grade 3 gastrointestinal toxicity was 3%. At least one episode of gastrointestinal bleeding on followup, which could be attributed to radiation, was recorded in 14.9% of patients. For patients achieving erections before radiation, the 3-year Kaplan-Meier potency preservation rate was 66.5%.nnnCONCLUSIONSnThe early toxicity of the combination of IG-IMRT and low-dose rate brachytherapy boost in this study was favorable.

The Allegheny Prostate Center: Comprehensive Evaluation and Unbiased Counseling on Treatment Options

a leader in innovative approaches to the delivery of healthcare. In the early 1990s, researchers began investigating cryosurgery for the treatment of tumors. Jeffrey Cohen, MD, and Ralph Miller, Jr., MD, urologists at Allegheny General Hospital, saw the potential for adapting this technology to treat their prostate cancer patients. These physician leaders then developed and pioneered a program for the treatment of prostate cancer with cryosurgery. As the technology developed and was described in medical and popular literature, the number of patients seeking cryosurgery at Allegheny General Hospital soon increased rapidly. For a variety of reasons, however, many men who presented with the intent of undergoing cryosurgery were not candidates for this procedure and instead were sent to see a radiation oncologist. It became obvious to both specialties that patients were presenting intent on cryosurgery but were not well informed about the myriad of other treatment options for prostate cancer. The urologists and radiation oncologists soon came to agree that the best way for patients to be fully informed about all the options for prostate cancer treatment was to talk with both specialties—ideally in a multidisciplinary clinic setting. The Allegheny Prostate Center