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.

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.

[A coherent radiotherapeutic-surgical approach, based on PSA, for the management of cancer of the prostate]. / Une approche radio-chirurgicale cohérente, basée sur le PSA, pour la prise en charge du cancer de la prostate.

The presence of cancer of the prostate does not mean that a patient will succumb to the disease. In fact, prior to the advent of prostate-specific antigen (PSA) testing, the cause of death in 50% of men with detectable extraglandular cancer was intercurrent disease. No studies have conclusively demonstrated a definitive benefit of surgery or radiation over simple observation; therefore treatment complications must absolutely be restricted to a bare minimum while demonstrating curative effect. This review presents a balanced perspective on the management of prostate cancer which results from non-adversarial, extensive, and continuous interactions between two very active Departments (Urology and Radiation Oncology). Such a multidisciplinary approach fosters relevant research projects and ultimately benefits patient care.

Radiotherapy planning for simulation of prostate cancer: computerized tomographic scanning vs. conventional radiographic localization.

A computerized tomographic localization protocol for prostate cancer treatment planning is described. In 23 patients, this new method is compared to localization using conventional orthogonal radiographic simulation with contrast media in the rectum, bladder, and urethra. Advantages of the CT localization protocol include enhanced ability to delineate the tumor extension, particularly for superior, lateral, anterior, and posterior spread. Accurate CT localization of the inferior border of the target volume has also been demonstrated to be feasible, thereby avoiding the need for invasive urethral, bladder, and rectal manipulations.

Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma.

Between 1978 and 1985, 393 of 2,765 (14%) patients with operable cancer of the breast (clinical stage T0-3N0-2M0) were irradiated after excisional biopsy and staging axillary dissection. Of 77 patients with microscopic axillary metastases, 68 received systemic adjuvant therapy. Treatment failed locally in 26 cases, and there were seven patients with distant metastasis. The three major factors for increased local treatment failure were (a) age below 40 years (P = .003), (b) negative estrogen receptor assay result (P = .03), and (c) failure to deliver a radiation boost dose when tumor was present at the margin of the specimen (P = .002). The size of the tumor, the nodal status, the progesterone receptor assay result, and the presence of ductal carcinoma in situ mixed with infiltrating carcinoma did not show a significant influence on local recurrence. In 274 of 393 (70%) patients, cosmesis was evaluated. The four major factors affecting cosmesis favorably were (a) utilization of a wedge (P less than .0001); (b) treatment of two fields a day (P less than .0001); (c) failure to use a separate treatment port to the regional lymph nodes, so as to avoid field junctions (P = .0003); and (d) small size of specimen (less than 50 cm2) (P = .0171). A second or third cancer was found in 39 of the 393 (10%) patients; contralateral breast cancer was the most common form (n = 23), followed by genitourinary cancer (n = 5). The most frequent complication was arm edema (6%).

Treatment selection for base of tongue carcinoma.

Sixty-two previously untreated patients with squamous cell carcinoma of the base of tongue were retrospectively analyzed. The American Joint Committee on Cancer (AJCC) Stage distribution was I-3, II-7, III-24, and IV-28. The choice of treatment was nonrandomized. The local control was 10/18 with high-dose preoperative radiation, 17/30 with external beam radiation only, and 4/14 with external beam plus interstitial implantation. The median survival for the three treatment regimens were 63, 51, and 13 months, respectively. Preoperative radiation is suggested for tumors with inferior (laryngeal) spread or those with extensive superior extension (to tonsillar fossa and beyond). For centrally placed lesions in the base of the tongue (with or without lateral hypopharyngeal wall spread), radiation alone is recommended. An interstitial implantation should be restricted to lesions equal to or less than 4 x 3 x 2.5 cm3. Since this insertion is technically more demanding than for tumors of the mobile tongue, they should be performed by the more experienced brachytherapist.

Observations on the treatment of mediastinal masses in Hodgkin's disease emphasizing site of failure.

Of 244 patients with Hodgkin's disease, 126 (52%) had an abnormal mediastinum. Sixty-four patients were treated with radiation, 36 with radiation and chemotherapy, and 25 with chemotherapy alone as an initial treatment. Twenty of 52 (38%) with stage I or II who received initially radiation alone relapsed, and 70% (14 of 20) of them were salvaged with chemotherapy. Therefore, the ultimate failure rate was 12% (6 of 52). Forty percent (8 of 20) of these patients failed within or at the margin of the radiation portal, and 60% failed predominantly outside of the radiation field. Even though we did not treat the whole lung prophylactically, there was only one true peripheral lung recurrence. Nine of 20 (45%) recurred in more than one site. Of 36 patients treated with combined radiation and chemotherapy, 21 patients had stage I, II, or IIIA disease. Of these, two patients relapsed. Of 86 patients with accessible x-ray films, 30 patients had large masses with a ratio of mass to transverse diameter greater than .33 at the broadest level. Fifty-six patients had small masses. Survival at 96 months in patients with stages I-IIIA with either large or small masses is 94% (p = 0.80). Their relapse-free survival at 96 months is 79% for large masses and 95% for small masses (p = 0.18). The site of relapse is discussed in detail in the text. There were five treatment-related deaths; three patients died of acute myelogenous leukemia. Our data do not support the role of whole-lung prophylactic irradiation or initial combined radiotherapy and chemotherapy in patients with large mediastinal masses.

Proposed method to study the factors affecting local control with combined external beam and interstitial implantation of mobile tongue and floor of mouth.

Twenty-seven patients with squamous cell carcinoma of the mobile tongue and floor of the mouth were treated with external beam and interstitial radiation. Good prognostic factors were T1N0, T2N0, superficial tumors, tumor shrinkage by 75% with external beam, and no apparent tumor clinically 2 months after treatment. On the other hand, T3N0, T1-3N1, and deeply necrotic tumors had a poor prognosis. We recommend using a flexible afterloading system to implant the initial local tumor volume (not just the residual nidus) that does not exceed 45 cm3. The minimum (reference) dose was prescribed to a surface 1/2 cm beyond the most peripheral rim of radioactive sources. For acceptable local control and complication rates, our suggested minimum (reference) doses are less than or equal to 7,500 rads for T1 (or a time-dose-fractionation [TDF] of 131-140), less than or equal to 8,000 rads for T2 (TDF of 131-140), and probably less than 8,500 rads for T3 (TDF of less than or equal to 150). These guidelines should be considered preliminary.

Reassessment of technical and biological factors in paranasal sinus carcinoma.

Twenty-seven patients with paranasal sinus carcinoma were analyzed. Local control with radiation alone was poor, with most patients failing centrally within the primary site. With preoperative radiation local control is 60%. Previous reports have emphasized failure at superior sites--particularly the orbit. The pattern of local failure in our series is predominantly various medial sites inclusive of intact or exenterated orbit. The surgically nonremovable medial structures are best encompassed by a three-field radiotherapy technique (weighted anterior and two laterals).

Management of gastrointestinal lymphoma.

A study was made of 65 patients with primary gastrointestinal (GI) lymphoma. The occurrence was 40 (62%) in stomach, 15 (23%) in the small intestine, and 10 (15%) in colorectum. The majority of patients had their histology classified according to Rappaport's classification. Diffuse histiocytic type had the worst prognosis (median survival 13.8 months), and nodular histology had the best prognosis. A modified staging system proposed by Blackledge et al. was used. Patients who had their disease confined to one viscus (Stage I) or with spread to regional lymph nodes (Stage II) had an excellent prognosis, with a 5-year survival of 87 and 67%, respectively. However, those who had distant nodal involvement (Stage III, e.g., para-aortic nodes) or spread to adjacent organs within the abdomen (Stage IV) had worse prognosis, with 5-year survival of 40 and 13%, respectively. In Stage I, radiotherapy alone was as effective as surgical resection. None of the 11 patients treated by radiotherapy alone had perforation or bleeding. The 5-year disease-free survival was 51%.

Carcinoma of the tonsillar area treated with external radiotherapy alone.

Seventy patients with carcinoma of the tonsillar area were treated with radiation therapy alone, all with a minimum follow-up of 3 years. Seventeen patients with stages I and II developed six recurrences and three were salvaged by surgery. Fifty-three patients with stages III and IV developed 24 recurrences, and only three could be salvaged by surgery. We conclude that radiation therapy is adequate for stages I and II carcinoma of the tonsillar area. Local control rate is satisfactory and surgical salvage is acceptable. Patients with advanced disease, Stages III and IV, have a poor survival rate with radiotherapy alone. Local recurrence is high and surgical salvage is inadequate. We have decided to offer selected patients with stages III and IV tonsillar carcinoma planned combined radiotherapy and surgery, in an effort to improve the survival rate.

Single- and double-plane iridium-192 interstitial implants: implantation guidelines and dosimetry.

Computerized dosimetric studies of single- and double-plane iridium-192 (Ir-192) planar implants were performed. With respect to dose homogeneity, we found that the optimal source and ribbon separation for single-plane implants was 1.0 cm. For double-plane implants, the preferred ribbon and plane separation was 1.5 cm, maintaining a 1-cm separation for the sources. Using these separations, standard dose rate curves for single- and double-plane Ir-192 implants were generated by computer calculations. These standard curves are useful for quickly and fairly accurately estimating the dose from any size planar implant, without requiring more time-consuming individual computer dosimetry. We believe that the curves will prove to be of practical clinical value to physicists and radiotherapists.

Local control of T1 vocal cord cancer with radiation therapy: the importance of tumor character vs. treatment parameters.

Ninety-one patients with T1 vocal cord carcinoma received primary irradiation treatment. The 5- and 10-year determinate disease-free survival was 80%; the 5- and 10-year determinate survival including surgical salvage was 92%. Tumors involving more than one-half of a vocal cord or involving the anterior commissure or exhibiting an exophytic growth pattern had numerically, but not statistically, higher local failure rates than tumors without these characteristics. Precise radiation treatment technique appears more important for local control (LC) than tumor character. The crucial treatment factors for high LC with few radiation complications are reproducible daily patient positioning, use of contour-compensating devices (wedges), field size of 5 X 5 cm, and a radiation prescription with a time-dose fractionation value of 101 to 106.

A 'watchful waiting' policy for in situ carcinoma of the vocal cords.

Forty-five patients with vocal cord (VC) carcinoma in situ diagnosed by biopsy or VC stripping have been retrospectively analyzed. Eighteen patients received irradiation therapy immediately on diagnosis. The initial local control (LC) rate was 72% (13/18); the salvage-augmented LC rate was 94% (17/18). Twenty-seven patients with in situ carcinoma were treated expectantly ("watchful waiting"), receiving definitive radiotherapy or definitive surgery only if invasion was subsequently verified histologically. One third of the patients' carcinomas have not become invasive (mean follow-up, 50 months). Of the two thirds that became invasive, one third were more advanced than T1N0 when treated--often because patients missed scheduled follow-up appointments. Nevertheless, the initial LC rate was 65% (11/17); the salvage-augmented LC rate was 88% (15/17). Total laryngectomy was required twice as often in the watchful waiting group as in the immediately treated group.

The management of carcinoma of the nasal vestibule.

Forty-two patients with squamous cell carcinoma of the nasal vestibule were reviewed. The patients were treated at either the Southern California Permanente Medical Group or the UCLA Medical Center. Thirty-eight patients (90%) had early lesions and 4 (10%) had late disease (involving the nodes or bone). The following conclusions were formed from this study: (1) Patients without bone destruction or lymph node metastases will do well with either irradiation or surgery. Those with bone destruction or lymph node metastases will do poorly in spite of radical treatment. (2) Early lesions can often be cured with either partial rhinectomy or irradiation. (3) A surgical recurrence following partial rhinectomy can be salvaged with irradiation. (4) A radiation recurrence of an early lesion can be salvaged with surgery. (5) The routine use of total rhinectomy for early carcinoma or radiation failure is unwarranted. (6) Other primary cancers are not uncommon when followup is extended to the 5- to 10-year interval.

Patterns of recurrence following curative resection alone for adenocarcinoma of the rectum and sigmoid colon.

Two-hundred-four patients with previously untreated adenocarcinoma of rectum, rectosigmoid, and sigmoid colon were retrospectively evaluated to determine patterns of recurrence following curative resection. Seventy-eight (38%) subsequently developed recurrent disease. Of these, 40% (31/78) presented with local recurrence alone, 28% (22/78) with regional recurrence, 15% (12/78) with concomitant local recurrence and distant metastasis, and 17% (13/78) with distant metastasis alone. The degree of tumor anaplasia and depth of tumor penetration into the bowel wall influenced the rate of local recurrence. Through five years local recurrence without clinical evidence of distant metastasis was the most common cause of death. Need for adjuvant radiation therapy is discussed.